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1.
Pediatr Obes ; 13(11): 705-714, 2018 11.
Article in English | MEDLINE | ID: mdl-29493105

ABSTRACT

BACKGROUND: Numerous studies have shown that there are links between obesity, liver fat and the gut microbiome. However, there are mixed results on whether probiotics could impact the gut microbiome and/or help to decrease liver fat and obesity outcomes. OBJECTIVE: This study aimed to determine whether a probiotic supplement (VSL#3® ) intervention altered gut microbiota and/or gut hormones associated with appetite regulation. The secondary aim of this study was to determine whether VSL#3® altered body composition and liver fat and fibrosis. METHODS: We conducted a double-blind, randomized placebo-controlled trial in 19 obese Latino adolescents. The intervention consisted of three packets per day of VSL#3® or a matched placebo for 16 weeks. Pre-intervention and post-intervention measures included gut microbial abundance, gut appetite regulating hormones, anthropometrics, body composition, liver fat and liver fibrosis. We conducted linear models to determine whether there were any significant differences in the changes in these outcomes following VSL#3® intervention. RESULTS: Compared with placebo, adolescents that received VSL#3 had significant increases in total adiposity (%) (+1.7 ± 0.6 vs. -1.3 ± 0.5, p < 0.01) and trunk adiposity (%) (+3.3 ± 0.8 vs. -1.8 ± 0.8, p < 0.01) with no significant effects on liver fat/fibrosis, insulin/glucose, gut microbial abundances or gut hormones. CONCLUSION: VSL#3 supplementation may lead to increased adiposity in obese Latino adolescents with no significant detectable changes in gut microbiota, gut appetite-regulating hormones, liver fat and fibrosis and dietary intake. However, it is important to note that recruitment efforts were terminated early and the sample size fell short of what was planned for this trial.


Subject(s)
Fatty Liver/physiopathology , Gastrointestinal Microbiome/physiology , Pediatric Obesity/therapy , Probiotics/therapeutic use , Adolescent , Anthropometry/methods , Appetite/physiology , Blood Glucose/analysis , Body Composition/physiology , Child , Double-Blind Method , Female , Hispanic or Latino/statistics & numerical data , Humans , Insulin/blood , Liver Cirrhosis/physiopathology , Male , Pediatric Obesity/microbiology , Pediatric Obesity/physiopathology , Probiotics/adverse effects
2.
Biochem Soc Trans ; 33(Pt 4): 867-72, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16042616

ABSTRACT

A general strategy for the expression of bacterial membrane transport and receptor genes in Escherichia coli is described. Expression is amplified so that the encoded proteins comprise 5-35% of E. coli inner membrane protein. Depending upon their topology, proteins are produced with RGSH6 or a Strep tag at the C-terminus. These enable purification in mg quantities for crystallization and NMR studies. Examples of one nutrient uptake and one multidrug extrusion protein from Helicobacter pylori are described. This strategy is successful for membrane proteins from H. pylori, E. coli, Enterococcus faecalis, Bacillus subtilis, Staphylococcus aureus, Microbacterium liquefaciens, Brucella abortus, Brucella melitensis, Campylobacter jejuni, Neisseria meningitides, Streptomyces coelicolor and Rhodobacter sphaeroides.


Subject(s)
Membrane Transport Proteins/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Biological Transport, Active , Circular Dichroism , DNA, Bacterial/genetics , Helicobacter pylori/chemistry , Helicobacter pylori/genetics , Helicobacter pylori/metabolism , Membrane Transport Proteins/chemistry , Membrane Transport Proteins/genetics , Models, Biological , Plasmids , Restriction Mapping , Symporters/genetics , Symporters/metabolism
3.
Eur J Neurosci ; 13(8): 1559-71, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11328350

ABSTRACT

The developing neocortex influences the growth of thalamocortical projections. Layer 4 in particular receives the majority of input from the thalamus and is important in instructing thalamic afferents to terminate. Previous in vivo experiments demonstrated that disruption of layer 4 during corticogenesis in ferret somatosensory cortex by application of methylazoxy methanol acetate (MAM) prevents proper termination of thalamic afferents in appropriate cortical regions. To further explore the role of layer 4 in thalamocortical development, we prepared organotypic cocultures consisting of normal gestational day 0 (P0) ferret thalamus paired with normal, embryonic day 33 (E33), or E38 MAM-treated cortex obtained from ferrets at either P0 or P7. Injection of MAM on E33 disrupts layer 4 formation, whereas similar injections on E38 interfere with layer 2 formation. The cocultures grew together for a number of days, then discrete injections of either fluorescent dextrans or 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) were made into the thalamic piece. The labeled thalamic afferents that grew into the cortical slice were analysed and the sites of their terminations quantified after 3, 5, or 7-10 days in culture (DIC). Our results varied somewhat with the amount of time in culture, but the preponderance of thalamic fibers in normal cortex terminated in layer 4, whereas their counterparts in E33 MAM-treated cortex grew beyond the cortical plate and many fibers terminated inappropriately within lower cortical layers or white matter. Terminal distribution of thalamic fibers in E38 MAM-treated cortex looked similar to normal. These results demonstrate that the cells of layer 4 provide thalamic afferents with important positional and termination cues.


Subject(s)
Cerebral Cortex/physiology , Neuronal Plasticity , Somatosensory Cortex/physiology , Synaptic Transmission/physiology , Thalamus/physiology , Afferent Pathways/physiology , Animals , Animals, Newborn/physiology , Brain Mapping , Bromodeoxyuridine/metabolism , Cerebral Cortex/drug effects , Cerebral Cortex/embryology , Ferrets , Fetus/physiology , Methylazoxymethanol Acetate/pharmacology , Organ Culture Techniques , Protein Synthesis Inhibitors/pharmacology , Time Factors
4.
J Neurosci ; 21(9): 3184-95, 2001 May 01.
Article in English | MEDLINE | ID: mdl-11312303

ABSTRACT

The precision of projections from dorsal thalamus to neocortex are key toward understanding overall cortical organization and function. To identify the significance of layer 4 cells in receiving the bulk of thalamic projections in somatosensory cortex, we disrupted layer 4 genesis and studied the effect on thalamic terminations in ferrets. Second, we ascertained the result of layer 4 disruption on functional responses and topographic organization. Methylazoxy methanol (MAM) was injected into pregnant ferrets on embryonic day 33 (E33), when most layer 4 neurons of somatosensory cortex are generated. This treatment resulted in dramatic reduction in the thickness of targeted layer 4. E38 MAM treatment was used as a control, when layer 2-3 neurons are generated. The projections of ventrobasal thalamus into somatosensory cortex were studied using DiI injections. We found only subtle differences between groups (normal, E33, or E38 MAM-treated) in the thalamic afferent pattern on postnatal day 1 (P1) and P7. On P14, thalamic terminations distribute almost equally throughout the remaining cortical layers in the E33 MAM-treated group compared with normal and E38 MAM-treated animals, in which the ventrobasal thalamus projects primarily to central layers. Electrophysiological recordings conducted on mature ferrets treated with MAM on E33 demonstrated that somatotopic organization and receptive field size are normal. These findings emphasize the importance of layer 4 in determining the normal laminar pattern of thalamic termination and suggest that, although its absence is likely to impact on complex neocortical functional responses, topographic organization does not arise from the influence of layer 4.


Subject(s)
Neural Pathways/cytology , Somatosensory Cortex/cytology , Thalamus/cytology , Animals , Behavior, Animal/drug effects , Bromodeoxyuridine , Cell Count , Cell Differentiation , Cell Movement/drug effects , Electrodes, Implanted , Female , Ferrets , Fluorescent Dyes , Methylazoxymethanol Acetate/analogs & derivatives , Methylazoxymethanol Acetate/pharmacology , Mitosis/drug effects , Morphogenesis/drug effects , Neural Pathways/drug effects , Neural Pathways/embryology , Physical Stimulation , Pregnancy , Prenatal Exposure Delayed Effects , Somatosensory Cortex/drug effects , Somatosensory Cortex/embryology , Teratogens/pharmacology , Thalamus/drug effects , Thalamus/embryology
5.
J Clin Oncol ; 19(8): 2302-8, 2001 Apr 15.
Article in English | MEDLINE | ID: mdl-11304784

ABSTRACT

PURPOSE: To examine two competing hypotheses relating to intellectual loss among children treated for medulloblastoma (MB): Children with MB either: (1) lose previously learned skills and information; or (2) acquire new skills and information but at a rate slower than expected compared with healthy same-age peers. PATIENTS AND METHODS: Forty-four pediatric MB patients were evaluated who were treated with postoperative radiation therapy (XRT) with or without chemotherapy. After completion of XRT, a total of 150 examinations were conducted by use of the child version of the Wechsler Intelligence SCALES: These evaluations provided a measure of intellectual functioning called the estimated full-scale intelligence quotient (FSIQ). Changes in patient performance corrected for age (scaled scores) as well as the uncorrected performance (raw scores) were analyzed. RESULTS: At the time of the most recent examination, the obtained mean estimated FSIQ of 83.57 was more than one SD below expected population norms. A significant decline in cognitive performance during the time since XRT was demonstrated, with a mean loss of 2.55 estimated FSIQ points per year (P =.0001). An analysis for the basis of the intelligence quotient (IQ) loss revealed that subtest raw score values increased significantly over time since XRT, but the rate of increase was less than normally expected, which resulted in decreased IQ scores. CONCLUSION: These results support the hypothesis that MB patients demonstrate a decline in IQ values because of an inability to acquire new skills and information at a rate comparable to their healthy same-age peers, as opposed to a loss of previously acquired information and skills.


Subject(s)
Cerebellar Neoplasms/psychology , Child Development , Cognition Disorders/etiology , Intelligence , Medulloblastoma/psychology , Adolescent , Cerebellar Neoplasms/complications , Child , Child, Preschool , Female , Humans , Infant , Learning , Longitudinal Studies , Male , Medulloblastoma/complications , Mental Processes
6.
J Clin Oncol ; 19(2): 472-9, 2001 Jan 15.
Article in English | MEDLINE | ID: mdl-11208841

ABSTRACT

PURPOSE: To test the hypothesis that inadequate development of normal-appearing white matter (NAWM) is associated with the relationship between young age at the time of craniospinal irradiation (CRT) and deficient neurocognitive performance in survivors of childhood medulloblastoma. PATIENTS AND METHODS: Forty-two patients treated since 1985 participated in this cross-sectional study. All had been treated with CRT with or without chemotherapy and had survived 1 or more years after treatment. Neurocognitive evaluations were conducted with tests of intellect (intelligent quotient; IQ), verbal memory, and sustained attention. Quantitative magnetic resonance imaging, using a hybrid neural network, assessed the volume of NAWM. RESULTS: Neurocognitive test results were below normal expectations for age at the time of testing. A young age at CRT was significantly associated with worse performance on all neurocognitive tests except that of verbal memory. An increased time from completion of CRT was significantly associated with worse performance on all neurocognitive tests except that of sustained attention. After statistically controlling for the effects of time from CRT, we examined the association of NAWM with neurocognitive test results. These analyses revealed that NAWM accounted for a significant amount of the association between age at CRT and IQ, factual knowledge, and verbal and nonverbal thinking, but not sustained attention or verbal memory. CONCLUSION: The present results suggest that, at least for some cognitive functions, deficient development and/or loss of NAWM after CRT may provide a neuroanatomical substrate for the adverse impact of a young age at the time of CRT.


Subject(s)
Cerebellar Neoplasms/radiotherapy , Cognition Disorders/etiology , Cranial Irradiation , Medulloblastoma/radiotherapy , Adolescent , Adult , Age Factors , Brain/pathology , Cerebellar Neoplasms/complications , Child , Child, Preschool , Cognition , Cognition Disorders/diagnosis , Cross-Sectional Studies , Female , Humans , Magnetic Resonance Imaging , Male , Medulloblastoma/complications , Psychological Tests , Risk Factors
7.
Chem Phys Lipids ; 108(1-2): 37-52, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11106781

ABSTRACT

Cannabinoids produce most of their biochemical and pharmacological effects by interacting with CB1 and CB2 cannabinoid receptors, both of which are G-protein coupled membrane-bound functional proteins. CB1 is found in the central nervous system and in a variety of other organs including heart, vascular endothelium, uterus, vas deferens, testis and small intestine. Conversely, the CB2 receptor appears to be associated exclusively with the immune system and is found in the periphery of the spleen and other cells associated with immunochemical functions. Although both CB1 and CB2 have been cloned and the primary sequences are known, their three dimensional structures and the amino acid residues at the active site, critical for ligand recognition, binding and activation have not been characterized. In the absence of any X-ray crystallographic and NMR data, information on the structural requirements for ligand-receptor interactions is obtained with the help of suitably designed molecular probes. These ligands either interact with the receptor in a reversible fashion (reversible probes) or, alternatively, attach at or near the receptor active site with the formation of a covalent bond (irreversible probes). Subsequently, information related to ligand binding and receptor activation is further amplified with the help of receptor mutants and computer modeling. This review focuses on molecular probes related to the classical and non-classical cannabinoids that have been reported since the discovery of the first cannabinoid receptor over a decade ago.


Subject(s)
Receptors, Drug/chemistry , Animals , Molecular Probes , Protein Conformation , Receptors, Cannabinoid , Receptors, Drug/metabolism , Structure-Activity Relationship
8.
J Pastoral Care ; 54(1): 63-73, 2000.
Article in English | MEDLINE | ID: mdl-11066755

ABSTRACT

Examines the efficacy of Lay Pastoral Telecare (LPT) on the spiritual well-being and church satisfaction of churchgoers (N = 207). Compares an experimental and a control group and concludes that the use of telephone by lay pastoral caregivers can be a means of promoting interpersonal support and enhancement of spiritual well-being within a church congregations.


Subject(s)
Christianity , Pastoral Care/methods , Social Support , Telephone , California , Female , Holistic Health , Humans , Interpersonal Relations , Male , Religion and Medicine , Research Design
9.
Curr Pharm Des ; 6(13): 1381-97, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10903399

ABSTRACT

During the past several years, cannabinoid biology has witnessed marked advances that has propelled it to the forefront of biomedical research. These new developments have also provided an opportunity to examine the physiological and biochemical events underlying the use and abuse of cannabis as well as elucidating the biological role of the endogenous cannabinoid ligands (endocannabinoids). The biological targets for endocannabinoids include the cannabinoid receptors (CB1 and CB2), the enzyme anandamide amidohydrolase (AAH), and the carrier protein referred to as the anandamide transporter (ANT). The identification of arachidonylethanolamide (anandamide, AEA) as an endogenous cannabinoid has been an important development in cannabinoid research which has led to the identification of two proteins associated with cannabinoid physiology in addition to the CB1 and CB2 receptors. These proteins are anandamide amidohydrolase (AAH), an enzyme responsible for the hydrolytic breakdown of anandamide and the anandamide transporter (ANT), a carrier protein involved in the transport of anandamide across the cell membrane. Evidence obtained so far suggests that these two proteins, in combination, are responsible for the termination of the biological actions of anandamide. Also, the discovery of anandamide has revealed a novel class of more selective agents possessing somewhat different pharmacological properties than the cannabinoids. A number of such analogs have now been reported many of which possess markedly improved cannabinoid receptor affinities and metabolic stabilities compared to those of the parent ligand. Generally, anandamide and all known analogs exhibit significant selectivities with high affinities for the CB1 receptor and modest to very low affinity for the CB2 receptor. In a relatively short period of time, pharmacological and biochemical studies have confirmed initial speculations that anandamide is either a neuromodulator or neurotransmitter and has significantly advanced our understanding of cannabinoid biochemistry. This summary seeks to define the pharmacology of endocannabinoids and to focus on the structure-activity relationships (SAR) of anandamide for the CB1 cannabinoid receptor.


Subject(s)
Arachidonic Acids/pharmacology , Cannabinoids/pharmacology , Receptors, Cell Surface/drug effects , Amidohydrolases/antagonists & inhibitors , Amidohydrolases/chemistry , Amidohydrolases/metabolism , Animals , Arachidonic Acids/biosynthesis , Arachidonic Acids/metabolism , Cannabinoid Receptor Modulators , Cannabinoids/chemistry , Cannabinoids/therapeutic use , Endocannabinoids , Humans , Polyunsaturated Alkamides , Structure-Activity Relationship
10.
Ann Neurol ; 46(6): 834-41, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10589535

ABSTRACT

Although previous studies have documented a significant risk of intellectual loss after treatment for childhood medulloblastoma (MED), the pathophysiology underlying this process is poorly understood. The purpose of this study was to test the hypotheses that (1) patients treated for MED in childhood have reduced volumes of normal white matter (NWM) related to their treatment with craniospinal irradiation with or without chemotherapy, and (2) deficits in NWM among patients surviving MED can at least partially explain deficits in their intellectual performance. Eighteen pediatric patients previously treated for MED were matched on the basis of age at the time of evaluation to 18 patients previously treated for low-grade posterior fossa tumors with surgery alone (mean difference, 3.7 months). Evaluations were conducted with age-appropriate neurocognitive testing and quantitative magnetic resonance imaging by using a novel automated segmentation and classification algorithm constructed from a hybrid neural network. Patients treated for MED had significantly less NWM (p < 0.01) and significantly lower Full-Scale IQ values than those treated for low-grade tumors (mean, 82.1 vs 92.9). In addition, NWM had a positive and statistically significant association with Full-Scale IQ among the patients treated for MED. We conclude that irradiation- or chemotherapy-induced destruction of NWM can at least partially explain intellectual and academic achievement deficits among MED survivors.


Subject(s)
Brain/pathology , Cerebellar Neoplasms/therapy , Cognition Disorders/etiology , Medulloblastoma/therapy , Neuropsychological Tests , Survivors , Adolescent , Algorithms , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Astrocytoma/physiopathology , Astrocytoma/psychology , Astrocytoma/therapy , Brain/anatomy & histology , Brain Neoplasms/physiopathology , Brain Neoplasms/psychology , Brain Neoplasms/therapy , Cerebellar Neoplasms/physiopathology , Cerebellar Neoplasms/psychology , Child , Combined Modality Therapy , Female , Humans , Magnetic Resonance Imaging , Male , Medulloblastoma/physiopathology , Medulloblastoma/psychology , Neural Networks, Computer , Radiotherapy/adverse effects , Wechsler Scales
11.
J Med Chem ; 42(10): 1828-35, 1999 May 20.
Article in English | MEDLINE | ID: mdl-10346935

ABSTRACT

The substrate properties of a series of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridinyl (MPTP) analogues in which the C-4 phenyl group has been replaced with various 4-azaaryl moieties have been examined in an effort to evaluate the contribution of electronic, polar, and steric parameters to the MAO-B-catalyzed oxidation of this type of cyclic tertiary allylamine to the corresponding dihydropyridinium metabolite. No significant correlation could be found with the calculated energy of the C-H bond undergoing cleavage. A general trend, however, was observed between the magnitude of the log P value with the magnitude of kcat/Km. The results indicate that the placement of a polar nitrogen atom in the space occupied by the phenyl group of MPTP leads to a dramatic decrease in substrate properties. Enhanced substrate properties, however, were observed when benzoazaarenes replaced the corresponding five-membered azaarenes. These results are consistent with our previously published molecular model of the active site of MAO-B.


Subject(s)
Aza Compounds/chemistry , Monoamine Oxidase/chemistry , Pyridines/chemistry , Animals , Catalysis , Cattle , Kinetics , Liver/chemistry , Structure-Activity Relationship , Substrate Specificity , Thermodynamics
12.
Cereb Cortex ; 9(2): 121-36, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10220225

ABSTRACT

Early generated layers of neocortex are important factors in forming the subsequent architecture of the cerebral cortex. To further explore the role of early generated cortex, we disrupted formation of an early generated cohort of cells by intraperitoneal injections of the mitotic inhibitor methylazoxymethanol (MAM) into pregnant ferrets timed to coincide with generation of subplate neurons in the ventricular zone. Our studies demonstrate that if early development of the neocortex is interrupted by injection of MAM during embryogenesis (on embryonic day 24 or 28; E24 or E28), a distinct laminar pattern fails to form properly in the parietal cortex. A reduced number of MAP2-positive cells were observed in the region of the subplate when compared with the number of MAP2-positive cells found in normal animals. Interference with the superficial neocortical layers that form later during development (on embryonic day 33) by appropriately timed MAM injections does not result in a severely disrupted laminar pattern. The interrupted laminar pattern that arises after early MAM injections coincides with distorted radial glial cells (identified by immunoreactivity to the intermediate filament protein, vimentin), which occur after early, but not late, MAM injections. Further analysis suggests that interference with early development of neocortex leads to premature differentiation of radial glial cells into astrocytes, as demonstrated by the presence of glial fibrillary acidic protein (GFAP). Experiments involving injections of the thymidine analog, bromodeoxyuridine (BRDU), demonstrated that 4 days after E24 MAM injection cells are generated and migrate into the thin cortical plate. By E38, however, cells continue to be generated in animals treated with MAM on E24 but do not reach their normal positions in the cortical plate. In addition, immunoreactivity using the CR50 antibody, which identifies presumptive Cajal-Retzius cells present in layer 1, demonstrates that the CR50-positive cells, normally precisely located in the outer portion of layer 1, are distributed in disarray throughout the thickness of the neocortex and intermediate zone in early MAM-treated animals, but not in those treated with MAM injections later during gestation. These findings are consistent with the idea that early generated layers are important in providing factors that maintain the environment necessary for subsequent neuronal migration and formation of neocortical layers.


Subject(s)
Neocortex/embryology , Neuroglia/pathology , Animals , Bromodeoxyuridine , Dextrans/pharmacology , Embryonic and Fetal Development/physiology , Female , Ferrets , Gestational Age , Immunohistochemistry , Neocortex/pathology , Parietal Lobe/embryology , Pregnancy
14.
J Med Chem ; 40(13): 1982-9, 1997 Jun 20.
Article in English | MEDLINE | ID: mdl-9207939

ABSTRACT

As part of our efforts to characterize more fully the structural features of the monoamine oxidase (MAO) A and B active sites, we have examined the substrate and inhibitor properties of several 1-methyl- and 1-cyclopropyl-4-aryl-1,2,3,6-tetrahydropyridine derivatives with the human placental A and beef liver B forms of the enzyme. We find that the 4-(2-phenylphenyl) analog 23 exhibits a high activity and selectivity for MAO-A while the 4-(3-phenylphenyl) analog 22 shows activity only with MAO-B. Selectivities similar to those of the N-methyl series are observed with a series of N-cyclopropyl mechanism based inactivators. These results support a topological analysis which attempts to identify steric factors related to the reported substrate and inhibitor selectivities of these two flavoproteins and provide a better definition of the size of the active sites of the two enzymes.


Subject(s)
Monoamine Oxidase/metabolism , Pyridines/chemistry , Animals , Binding Sites , Cattle , Humans , Kinetics , Liver/enzymology , Models, Chemical , Models, Molecular , Monoamine Oxidase/chemistry , Placenta/enzymology , Pyridines/metabolism
15.
J Comp Neurol ; 374(2): 259-77, 1996 Oct 14.
Article in English | MEDLINE | ID: mdl-8906498

ABSTRACT

Ferrets have become recognized as a useful and interesting model for study of neocortical development. Because of their immaturity at birth, it is possible to study very early events in the ontogeny of the brain. We used living slices of ferret somatosensory cortex to study the formation and development of intrinsic elements within the neocortex. A small number of fixed, hemisected brains injected with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) were also used. The slices were obtained from ferret kits aged postnatal day (P)1 to P62 and maintained in a chamber; each slice received injections of fluorescent-labeled dextrans. The injections were made at different ages in several distinct sites, which included the proliferative ventricular zone, the intervening white matter (or intermediate zone), and different sites of developing cortex, including the deeper cortical plate, which incorporated the subplate in young animals, and more superficial cortical sites depending on the age of the animal. Several animals also received injections into the ventrobasal thalamus. Injections into young animals (P1-7) produced a dominant radial pattern that extended from the ventricular zone into the cortex. Injections into the ventricular zone labeled many cells that appeared morphologically like radial glia as well as presumptive neurons. Although the predominant pattern was radial, injections in the ventricular zone often produced tangentially oriented cells and horizontally arranged fibers at the outer edge of the proliferative zone. These cells and fibers may provide a substrate for tangential dispersion of neurons within the neocortex. More superficial injections within the slice labeled lines of cells that appeared to be stacked upon one another in a radial pile in the cortex; the cortical plate received very few lateral projections. Data obtained from more mature slices indicated that although the overall pattern of staining remained radial, the precise character of the pattern changed to include more lateral spread into surrounding cortex, which eventually refined and developed into distinct patches by P28, when the overall cortical architecture appeared adult like. The data involving thalamocortical connections were more limited, but they indicated that the thalamus projects precisely to the somatosensory cortex in a point-to-point fashion from the earliest date studied (P0) and that the ventrobasal nucleus terminates upon the somatosensory cortex in a patchy manner during the early postnatal days of development. This study of the development of the somatosensory cortex confirms the ubiquitous nature of column-like connections throughout the neocortex and provides a novel view of the radial nature of early neocortical maturation.


Subject(s)
Neural Pathways/growth & development , Somatosensory Cortex/growth & development , Animals , Female , Ferrets , Histocytochemistry , Male , Neural Pathways/anatomy & histology , Somatosensory Cortex/anatomy & histology
16.
Ophthalmology ; 103(4): 670-3, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8618769

ABSTRACT

PURPOSE: To determine Schirmer wetting (tear flow) in patients before and after kidney transplantation where systemic cyclosporine was used as an immunosuppressive. METHODS: Patients with end-stage renal disease who received living donor or cadaveric kidney transplants and simultaneous systemic cyclosporine were recruited. A 4-minute Schirmer test with topical anesthetic was performed in both eyes of each person before cyclosporine was initiated and three times after transplantation. The tear flow values from both eyes were averaged before analysis. RESULTS: Tear flow increased significantly from precyclosporine levels of 19.4 +/- 1.5 mm/4 minutes (mean +/- standard error of the mean, n = 7; readings at 1 to 3 days before cyclosporine was begun) to 28.4 +/- 2.4 mm/4 minutes at 1 to 2 months after cyclosporine (P < 0.01), 26.4 +/- 2.0 mm/4 minutes at 3 to 5 months (P < 0.05), and 24.4 +/- 2.1 mm/4 minutes at 9 to 18 months (P < 0.05) after initiation of cyclosporine therapy. No relation existed between tear flow and systemic cyclosporine concentration. CONCLUSION: Tear flow was significantly enhanced by systemic cyclosporine when given to renal allograft recipients as an immunosuppressive. The increased flow rate was sustained over the maximum follow-up of 18 months and indicates an unexpected, beneficial side effect of cyclosporine, even in the absence of a deficit in baseline tear production.


Subject(s)
Cyclosporine/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Tears/metabolism , Adult , Female , Graft Rejection/drug therapy , Humans , Kidney Failure, Chronic/surgery , Lacrimal Apparatus/metabolism , Longitudinal Studies , Male , Middle Aged , Tears/drug effects
17.
Ophthalmology ; 102(1): 118-21, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7831025

ABSTRACT

PURPOSE: To measure tear flow in renal allograft recipients who received oral cyclosporine as immunosuppressive therapy. PATIENTS: Control subjects were from the staff of various clinics, dialysis patients were recruited, and one group of kidney transplant recipients took oral cyclosporine, whereas another group took azathioprine. Written informed consent was obtained for an institutionally approved protocol. METHODS: A 4-minute Schirmer test with topical anesthetic was performed in both eyes of each person, and the average score was used in calculations. RESULTS: The tear flow rate was 10.6 mm/4 minutes in the control subjects, 13.6 mm/4 minutes in the dialysis patients, 10.4 mm/4 minutes in kidney transplant recipients taking azathioprine, and 19.0 mm/4 minutes in kidney transplant recipients taking cyclosporine. Kidney transplant recipients taking cyclosporine had significantly increased tear flow compared with the other three groups (P < 0.05); dialysis patients, kidney transplant recipients taking azathioprine, and control subjects showed statistically indistinguishable tear flow. Within-group comparisons (male versus female, black versus white, and all combinations) showed no statistically significant differences. CONCLUSION: Medications used by dialysis patients or the azathioprine group did not significantly increase tear flow compared with control subjects. The addition of cyclosporine (plus prednisone) enhanced tear flow in kidney transplant recipients compared with all other groups. Systemic cyclosporine appears to increase tear flow even when no lacrimal autoimmune disease exists.


Subject(s)
Cyclosporine/therapeutic use , Tears/drug effects , Adult , Azathioprine/therapeutic use , Female , Humans , Kidney Failure, Chronic/therapy , Kidney Transplantation , Male , Middle Aged , Reference Values , Renal Dialysis
18.
J Appl Physiol (1985) ; 76(2): 853-8, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8175599

ABSTRACT

Glucose production during insulin-induced hypoglycemia in the fasted state is heavily dependent on the process of hepatic gluconeogenesis. Skeletal muscle glycogen is one possible source of lactate for hepatic gluconeogenesis. Fructose 2,6-bisphosphate (F-2,6-P2) and glucose 1,6-bisphosphate (G-1,6-P2) are two allosteric activators of muscle glycolysis. To investigate their putative role in the control of muscle lactate production during hypoglycemia, fasted rats were infused via jugular catheters with insulin in 0.9% NaCl or with 0.9% NaCl alone for 60 or 120 min. Muscles were removed and clamp frozen in liquid nitrogen. The insulin infusion produced plasma insulin values of 97 +/- 13 microU/ml after 1 h and 100 +/- 9 microU/ml after 2 h. Blood glucose in the saline-infused rats was 4.6 +/- 0.2 mM after 1 h and 5.1 +/- 0.1 mM after 2 h compared with 1.5 +/- 0.01 and 1.0 +/- 0.1 mM after 1 and 2 h, respectively, in the insulin-infused rats. The hypoglycemic rats had significantly elevated plasma epinephrine and blood lactate levels compared with the saline-infused rats. F-2,6-P2 and G-1,6-P2 were increased two- to five-fold in white quadriceps of hypoglycemic rats compared with that of saline-infused rats. The results are consistent with F-2,6-P2 and G-1,6-P2 playing a role in stimulating muscle lactate production as a source of gluconeogenic substrate during insulin-induced hypoglycemia.


Subject(s)
Fructosediphosphates/metabolism , Glucose-6-Phosphate/analogs & derivatives , Glucosephosphates/metabolism , Hypoglycemia/chemically induced , Hypoglycemia/metabolism , Insulin , Muscles/enzymology , Animals , Cyclic AMP/metabolism , Glycogen/metabolism , Insulin/blood , Liver/metabolism , Male , Osmolar Concentration , Rats , Rats, Sprague-Dawley
19.
Am J Cardiol ; 73(2): 113-6, 1994 Jan 15.
Article in English | MEDLINE | ID: mdl-8296730

ABSTRACT

There is controversy concerning the relative safety and efficacy of the 2 currently available percutaneous transluminal coronary angioplasty dilatation systems--fixed-wire (FW) and over-the-wire (OW). A randomized, prospective trial comparing the 2 systems was performed to examine this controversy. Of 1,513 patients undergoing percutaneous transluminal coronary angioplasty at 3 centers between June 1990 and October 1991, 602 (40%) fulfilled the eligibility criteria for the study. There were 643 lesions, of which 327 were randomized to FW and 316 to OW systems. There was no difference in the success rate between FW (92%) and OW (94%) systems. Inability to cross with a wire was infrequent with either system (FW: 1.8%; and OW: 1.6%). Inability to cross with a balloon when the wire crossed the lesion did not occur. An FW system was successful in 6 cases (1.9%) in which the OW system had been unsuccessful, whereas an OW system succeeded in 14 (4.3%) after the FW system had been unsuccessful (p = NS). Time to cross stenoses was 200 +/- 21 and 233 +/- 22 seconds, procedural time was 21 +/- 1.3 and 21 +/- 1.0 minutes, fluoroscopy time was 6.7 +/- 0.4 and 7.1 +/- 0.4 minutes, contrast used was 89.0 +/- 4.2 and 84.0 +/- 3.5 ml, and number of cine runs was 5.9 +/- 3.0 and 6.3 +/- 3.4 in the FW and OW systems, respectively. Complications were infrequent with either system (FW: 10.4%; and OW: 9.5%). Acute closure occurred in 1.8 and 2.2% of cases in the FW and OW systems, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Aged , Equipment Design , Female , Humans , Male , Middle Aged , Prospective Studies
20.
Cathet Cardiovasc Diagn ; 29(4): 267-72, 1993 Aug.
Article in English | MEDLINE | ID: mdl-8221844

ABSTRACT

This study describes a method for the performance of cardiac catheterization using 5 French preformed Judkins catheters from a percutaneous right brachial approach, and compares that technique to the more traditional percutaneous right femoral approach with 6 French catheters. One hundred consecutive patients requiring diagnostic left heart catheterization and selective coronary angiography were randomized according to femoral versus brachial arterial technique. Procedural efficiency, radiation exposure, and diagnostic film quality favored the femoral approach, while patient comfort, hemostasis time, time to ambulation, and decreased need for post-procedure nursing care favored the brachial approach. No differences were identified in complications. Cardiac catheterization from a right brachial artery percutaneous approach with 5 French preformed catheters has both advantages and disadvantages when compared with a more traditional femoral approach with 6 French catheters. Multiple factors should be considered before selecting an approach to diagnostic cardiac catheterization and each patient should be individually evaluated for determination of the optimal technique.


Subject(s)
Cardiac Catheterization/instrumentation , Coronary Angiography/instrumentation , Coronary Disease/diagnostic imaging , Brachial Artery , Cineangiography/instrumentation , Early Ambulation , Female , Femoral Artery , Humans , Male , Middle Aged , Time Factors
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