Expression profile of rice Hsp genes under anoxic stress.

Although flooding is one of the most important environmental stresses worldwide, not all plant species are intolerant to its effects. Species from semi-aquatic environments, such as rice, have the capacity to cope with flooding stress. Heat-shock proteins (Hsps) are thought to contribute to cellular homeostasis under both optimal and adverse growth conditions. Studies of gene expression in plants exposed to low levels of oxygen revealed the up-regulation of Hsp genes. However, it is not clear whether Hsp genes are transcribed as a function of tolerance or whether they represent a response to anoxic stress. Therefore, the accumulation of Hsp gene transcripts was investigated in two different cultivars, "Nipponbare" (flooding tolerant) and "IPSL 2070" (flooding sensitive), subjected to anoxic stress. Fifteen-day-old rice root seedlings from both cultivars were used. Four different treatments were performed: no anoxia (control); 24-h anoxia; 48-h anoxia; and 72-h anoxia. Anoxic stress was confirmed by the increased gene expression of alcohol dehydrogenase. The data obtained showed that both rice cultivars ("Nipponbare" and "IPSL 2070") accumulated Hsp gene transcripts under anoxic stress; however, the majority of the Hsp genes evaluated were responsive to anoxic stress in "IPSL 2070" (flooding sensitive), whereas in "Nipponbare" (flooding tolerant), only six genes were highly up-regulated. This suggests that although Hsps have an important role in the response to anoxia, they are not the major cause of tolerance.

Hernia de Amyand, reporte de un caso / Amyand's hernia, a case report

Introducción: La hernia de Amyand es la presencia del apéndice cecal en el interior de una hernia inguinal, observándose en el 0,5-1% del total de hernioplastías en los adultos. Presentación del caso: Mujer de 81 años ingresó al servicio de urgencias por dolor en fosa iliaca derecha de una semana de evolución, de intensidad progresiva, asociado a aumento de volumen inguinal derecho, redondo de 10 centímetros de diámetro, sensible a la palpación, no reductible y sin signos de irritación peritoneal. Se decidió realizar intervención quirúrgica por sospecha de hernia inguinal derecha complicada, evidenciándose contenido purulento entre asas intestinales, el cual se drenó, descubriéndose el apéndice cecal en el interior del saco herniario, de aspecto necrótico y perforado, procediéndose a realizar apendicectomía más hernioplastia. La paciente evoluciona en el postoperatorio con cuadro bronquial obstructivo, el cual se trató con antibioticoterapia, respondiendo favorablemente, otorgándose el alta 13 días después de la cirugía. Discusión: El 6,7% de las causas de abdomen agudo en adultos mayores se deben a cuadros apendiculares, mientras que un 13,3% se deben a hernias complicadas. Sin embargo es extremadamente infrecuente encontrar el apéndice cecal inflamado intraherniano, lo que ocurre aproximadamente en el 0,1% de todas las apendicectomías. El cuadro clínico consiste en síntomas inespecíficos con confirmación usualmente intraoperatoria. Se ha descrito el diagnóstico pre-quirúrgico imagenologico con tomografía computarizada (TC). El tratamiento consiste en dos procedimientos: apendicectomía con aseo de la cavidad y la reparación del defecto herniario.

Introduction: Amyand's hernia is the presence of cecal appendix within an inguinal hernia, observed in 0.5-1% of total hernioplasties in adults. Case Report: 81 year old woman admitted to the emergency room for pain in the right iliac fossa, one week of evolution, progressive in intensity associated with an increase in right round inguinal volume, 10 centimeters (cm) in diameter, sensitive to palpation, non reducible without signs Peritoneal irritation. It was decided to undergo surgery for suspicion of complicated right inguinal hernia, showing purulent contents between the intestinal loops, which managed to drain, discovering the cecal appendix in the sack of necrotic and perforated inguinal hernia, proceeding to the subsequent appendectomy of hernioplasty. Postoperatively, the patient developed bronchial obstruction, which was treated with antibiotics, responding favorably, granting discharge 13 days after surgery. Discussion: 6.7% of the causes of acute abdominal pain in older adults are due to appendiceal pictures, while 13.3% are due to complicated hernias. However it is extremely rare to find the intraherniano inflamed cecal appendix, which occurs in approximately 0.1% of all appendectomies. The clinical picture is nonspecific symptoms usually intraoperative confirmation. It described the pre-surgical diagnosis imaging with computed tomography (CT). Treatment consists of two procedures: appendectomy with toilet cavity and repair of the hernia defect

'If at first you don't succeed, try again'. Looking beyond the initial results of a failed tuberculosis diagnosis.

We report the outcome of investigations conducted in 73 human immunodeficiency virus (HIV) infected Ugandan adults presumed to have pulmonary tuberculosis (PTB). Following initial investigations, 32 of 73 patients were diagnosed with PTB. Of the remaining 41 patients initially classified as 'non-PTB', six had a delayed PTB diagnosis after a median of 6 weeks. Of the six patients lost to follow-up, four (66%) were reported to have died. Active tracking and close monitoring of HIV-infected patients presumed to have PTB independently of initial investigation results may reduce morbidity and mortality among this vulnerable patient group.

Nous rapportons le résultat d'investigations réalisées chez 73 adultes Ougandais positifs au virus de l'immunodéficience humaine (VIH) et présumés d'avoir une tuberculose pulmonaire (TBP). Après les investigations initiales, 32 de 73 patients ont eu un diagnostic de TBP. Sur les 41 patients restants initialement classés comme « pas de TBP ¼, six ont eu un diagnostic de TBP retardé après un délai médian de 6 semaines. Sur les six patients perdus de vue, quatre (66%) sont décédés. Une recherche active et un suivi rapproché des patients VIH positifs présumés d'avoir une TBP indépendamment des résultats des investigations initiales pourrait réduire la morbidité et la mortalité dans ce groupe de patients vulnérables.

En el presente artículo se comunican los resultados de las investigaciones realizadas en 73 adultos ugandeses aquejados de infección por el virus de la inmunodeficiencia humana (VIH), en quienes existía la presunción clínica de tuberculosis pulmonar (TBP). Tras los exámenes iniciales se emitió el diagnóstico de TBP en 32 de los 73 pacientes. De los 41 pacientes restantes, clasificados inicialmente 'sin TBP', este diagnóstico se estableció de manera tardía en seis de ellos y la mediana del plazo hasta el diagnóstico fue 6 semanas. Se notificó la defunción de cuatro de los seis pacientes perdidos de vista durante el seguimiento (66%). La localización activa y el seguimiento estrecho de los pacientes con infección por el VIH y presunción clínica de TBP, sea cual fuere el resultado de las investigaciones iniciales, disminuirían la morbilidad y mortalidad en este grupo de pacientes vulnerables.

How precise is the PRECICE compared to the ISKD in intramedullary limb lengthening? Reliability and safety in 26 procedures.

BACKGROUND AND PURPOSE: The PRECICE intramedullary limb lengthening system uses a new technique with a magnetic rod and a motorized external remote controller (ERC) with rotational magnetic field. We evaluated the reliability and safety of the PRECICE system. METHODS: We compared our preliminary results with PRECICE in 24 patients (26 nails) with the known difficulties in the use of mechanical lengthening devices such as the ISKD. We used the Paley classification for evaluation of problems, obstacles, and complications. RESULTS: 2 nails were primarily without function, and 24/26 nails lengthened over the desired distance. Lengthening desired was 38 mm and lengthening obtained was 37 mm. There were 2 nail breakages, 1 in the welding seam and 1 because of a fall that occurred during consolidation. ERC usage was problematic mostly in patients with femoral lengthening. Adjustment of the ERC was necessary in 10 of 24 cases. 15 cases had implant-associated problems, obstacles were seen in 5 cases, and complications were seen in each of 4 cases. INTERPRETAION: The reliability of the PRECICE system is comparable to that of other intramedullary lengthening devices such as the ISKD. The motorized external remote controller and its application by the patients is a weak point of the system and needs strict supervision.

Reconstruction of forearm deformity by distraction osteogenesis in children with relative shortening of the ulna due to multiple cartilaginous exostosis.

BACKGROUND: In patients with multiple cartilaginous exostosis, distal ulnar osteochondromas frequently cause forearm deformities, with relative ulnar shortening, wrist joint deviation, and varus bowing. Progressive deformation often leads to pain, functional impairment, and cosmetic problems. Surgical ulnar lengthening is necessary to restore the carpal balance. The results of fixator-controlled ulnar lengthening were investigated in this study, using appropriate clinical and radiologic parameters and focusing on medium-term functional and structural outcomes. METHODS: Twelve children (3 boys, 9 girls; mean age 9.8 y) with multiple cartilaginous exostosis-induced ulnar shortening treated with fixator-controlled ulnar callotasis were evaluated retrospectively based on clinical and radiographic examinations preoperatively, after fixator removal, and at a follow-up investigation. Subjective symptoms and objective joint function were assessed clinically, whereas the extent of ulnar shortening, radial articular angle, carpal slip, and radial head dislocation were determined radiographically. RESULTS: The average follow-up period was 24.6 months. The mean ulnar shortening and radial articular angle improved significantly, from 14.3 mm or 38.7 degrees preoperatively to 1.7 mm or 25.6 degrees after fixator removal and showed a slight but significant increase to 5.2 mm or 30.1 degrees at the follow-up. Carpal slip and radial head dislocation remained unchanged. With the exception of radial abduction, no notable functional advancement was observed. One unintended ulnar overlengthening with a subsequent ulnocarpal impaction syndrome, one premature callus consolidation, and two fixator dislocations were noted. CONCLUSIONS: In agreement with literature reports, carpal balance can be restored over the medium term. However, mild recurrences of ulnar shortening and radial malformation were observed during further development. To prevent deformity progression in immature patients, surgery should be carried out early. The optimal timing of surgery needs to be calculated precisely to take advantage of the high remodeling potential and an acceptable degree of recurrent deformity. Ulnar lengthening is necessary, but overcorrection is inadvisable due to possible ulnocarpal impaction syndrome. As significant remodeling effects on the radius were observed, simultaneous radial correction procedures are not recommended a priori.

Oxidative stress markers in young hemodialysis patients - a pilot study.

AIMS: Studies in young hemodialysis patients without significant comorbidities might increase the understanding of incipient vascular pathology in uremia. We investigated whether a specific pattern of oxidative stress markers with potential prognostic significance could be identified in this population. MATERIAL AND METHODS: We performed a cross-sectional matched case control study of 25 young hemodialysis patients (age 18 - 40 years) without known comorbidity factors. Patients were matched pairwise to healthy controls, and markers of oxidative stress were analyzed for associations with surrogate parameters of vascular structure and function. RESULTS: Oxidized low-density lipoproteins (OxLDL) were similar in patients and controls whereas conjugated dienes were increased in the very low-density lipoproteins (VLDL) fraction (20 +/- 6 vs. 12 +/- 5 micromol/l, p < 0.0001), but not in the low-density lipoproteins (LDL) fraction (16 +/- 6 vs. 18 +/- 6 micromol/l). Superoxide dismutase (SOD) activity was diminished in patients (1,117 +/- 151 vs. 1,299 +/- 88 U/g Hb, p < 0.0001), but there was no difference in glutathione peroxidase (GPx) activity. Oxidative stress expressed as the ratio of oxidized and reduced glutathione (GSSG/GSH) was increased in patients (0.25 +/- 0.18 vs. 0.13 +/- 0.04, p = 0.0048). Intima-media thickness (IMT) of the common carotid artery (0.70 +/- 0.12 vs. 0.62 +/- 0.08 mm, p = 0.0007) was significantly increased, and postischemic peak flow (PIPF) by venous occlusion plethysmography was severely diminished in patients (632 +/- 319 vs. 1,057 +/- 543% of basal flow, p < 0.0001). None of the markers of oxidative stress was independently associated with IMT or PIPF or a significant discriminator between patients and controls by multivariate regression. CONCLUSIONS: In this pilot study of exclusively young patients on hemodialysis, oxidative stress markers were of limited clinical value in identifying young patients at risk for vascular complications.

Role of C-type lectins in mycobacterial infections.

Worldwide clinical cases due to multi drug- and extensively drug-resistant strains of Mycobacterium tuberculosis (M.tb) are increasing making the need for new therapies more critical than ever. A major obstacle for designing new drugs to treat mycobacterial infections is our limited knowledge of the interface between the bacillus (especially M.tb) and its host. The pulmonary innate immune system plays a key role in the recognition of microbes entering via the respiratory route. Although the specificity of this system is broad and based on the recognition of pathogen-associated molecular patterns (PAMPs), it is uniquely regulated to limit inflammation and thereby prevent damage to the gas-exchanging alveoli. Pulmonary surfactant proteins A and D (SP-A and SP-D) are collagenous, soluble, C-type (Ca(2+)-dependent) lectins (named collectins) of the lung innate immune system that are secreted into the alveoli by resident type II alveolar epithelial cells and distal bronchiolar Clara cells. The related collectin in serum, mannose-binding lectin/protein (MBL or MBP), provides first-line defense against several microbes. Phagocytes represent the first cellular defense in the alveoli and their surface is rich in C-type lectin pattern recognition receptors (PRRs), including the mannose receptor (MR), dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) and DC-associated C-type lectin-1 (Dectin-1). This review will discuss the important roles of the cell-associated C-type lectin PRRs and soluble collectins in the innate immune response to mycobacterial infections, and will present the current state of knowledge regarding the potential uses of these C-type lectins in therapy against infections, focusing on M.tb.

Estimation of premorbid cognitive function based on word knowledge: the Swedish Lexical Decision Test (SLDT).

In clinical neuropsychology, the present status of a patient is evaluated in relation to the assumed premorbid status. However, in Sweden, existing methods to assess premorbid status are far from optimal. In the present study, the design and evaluation of a Swedish Lexical Decision Test (SLDT) for premorbid global cognitive function (i.e., premorbid intelligence) is described. The design was based on the empirical finding that, in general adult population, word knowledge is strongly associated with measures of global cognitive functioning. Linear stepwise regression analysis demonstrated that SLDT findings accounted for 48% of the variance of global cognitive function as assessed by the Full Scale Intelligence Quotient (FSIQ) from the Wechsler Adult Intelligence Scale Revised (WAIS-R). Demographic variables alone accounted for 31% and a combination of SLDT results and demographics accounted for 60%. Psychometric properties are presented using data from 109 healthy individuals stratified according to age, gender, and level of education. In addition, a case of Alzheimer's disease is presented to illustrate the relationship between SLDT performance and cognitive function. Finally, the theoretical foundation for the relationship between word knowledge and global cognitive function is discussed.

Endogenous coenzyme A glutathione disulfide in human myocardial tissue.

Besides its role as a mechanical pump, the human heart serves as an endocrine organ, where known and as yet unknown hormones are produced. It is very likely that these hormones play an important role in cardiovascular regulation. In this study, a new endogenous vasoactive substance, coenzyme A glutathione disulfide (CoASSG), was isolated and identified in myocardial tissue. Human myocardial tissue was extracted with perchloric acid and fractionated by size exclusion-, displacement-, anion-exchange- and reversed-phase chromatography. In one fraction purified to homogeneity, CoASSG was identified by matrix assisted laser desorption/ionization (MALDI) mass-spectrometry, post-source decay MALDI-mass spectrometry and enzymatic structure analysis. Furthermore, CoASSG was also isolated from human cardiac specific granules. CoASSG has potent vasoconstrictive and proliferative effects. Therefore, CoASSG may affect myocardial function as an endocrine or autocrine substance after being released from myocardial specific granules.

Isolation and quantification of dinucleoside polyphosphates by using monolithic reversed phase chromatography columns.

In former studies, dinucleoside polyphosphates were quantified using ion-pair reversed-phase perfusion chromatography columns, which allows a detection limit in the micromolar range. The aim of this study was both to describe a chromatographic assay with an increased efficiency of the dinucleoside separation, which enables the reduction of analytical run times, and to establish a chromatographic assay using conditions, which allow MALDI-mass spectrometric analysis of the resulting fractions. We compared the performance of conventional silica reversed phase chromatography columns, a perfusion chromatography column and a monolithic reversed-phase C18 chromatography column. The effects of different ion-pair reagents, flow-rates and gradients on the separation of synthetic diadenosine polyphosphates as well as of diadenosine polyphosphates isolated from human platelets were analysed. Sensitivity and resolution of the monolithic reversed-phase chromatography column were both higher than that of the perfusion chromatography and the conventional reversed phase chromatography columns. Using a monolithic reversed-phase C18 chromatography column, diadenosine polyphosphates were separable baseline not only in the presence of tetrabutylammonium hydrogensulfate (TBA) but also in the presence of triethylammonium acetate (TEAA) as ion-pair reagent. The later reagent is useful because, in contrast to TBA, it is compatible with MALDI mass-spectrometric methods. This makes TEAA particularly suitable for identification of unknown nucleoside polyphosphates. Furthermore, because of the lower backpressure of monolithic reversed-phase chromatography columns, we were able to significantly increase the flow rate, decreasing the amount of time for the analysis close to 50%, especially using TBA as ion-pair reagent. In summary, monolithic reversed phase C18 columns markedly increase the sensitivity and resolution of dinucleoside polyphosphate analysis in a time-efficient manner compared to reversed-phase perfusion chromatography columns or conventional reversed-phase columns. Therefore, further dinucleoside polyphosphate analytic assays should be based on monolithic silica C18 columns instead of perfusion chromatography or conventional silica reversed phase chromatography columns. In conclusion, the use of monolithic silica C18 columns will lead to isolation and quantification of up to now unknown dinucleoside polyphosphates. These chromatography columns may facilitate further research on the biological roles of dinucleoside polyphosphates.

A prospective study of Plasmodium falciparum multiplicity of infection and morbidity in Tanzanian children.

Several studies suggest that in individuals with substantial previous exposure to malaria, co-infection with multiple clones of Plasmodium falciparum can protect against subsequent clinical malaria attacks. Other studies, mainly of individuals with little previous exposure, found the converse relationship. To test whether acquisition of such cross-protection tracks the acquisition of clinical immunity in general, 610 Tanzanian children aged 0-6 years were enrolled in a nine-month prospective study of the risk of morbidity in relation to parasitological status and merozoite surface protein 2 genotypes on enrolment. Prevalence of parasitaemia and multiplicity of infection increased with age. In the first year of life, the incidence of clinical malaria was almost three times higher in children with parasites at baseline than in those without. In older children, baseline P. falciparum infections appeared to protect against both parasitaemic and non-parasitaemic fever episodes. In children aged less than three years, baseline multiple infection tended to be associated with higher prospective risk of clinical malaria than single infection while in children aged more than three years the converse was found, but these effects were not statistically significant. These results provide further evidence that relationships between asymptomatic malaria infections and clinical malaria change with cumulative exposure.

Identification of dinucleoside polyphosphates in adrenal glands.

Dinucleoside polyphosphates have been characterised as extracellular mediators controlling numerous physiological functions like vascular tone or cell proliferation. Here we describe the isolation and identification of dinucleoside polyphosphates Ap(n)A (with n=2-3), Ap(n)G (with n=2-6) as well as Gp(n)G (with n=2-6) from adrenal glands. These dinucleoside polyphosphates are localised in granules of the adrenal glands. The dinucleoside polyphosphates diadenosine diphosphate (Ap(2)A), diadenosine triphosphate (Ap(3)A), adenosine guanosine polyphosphates (Ap(n)G) and diguanosine polyphosphates (Gp(n)G), both with phosphate group (p) numbers (n) ranging from 2 to 6, were identified by fractionating them to homogeneity by preparative size-exclusion- and affinity-chromatography as well as analytical anion-exchange and reversed-phase-chromatography from deproteinised adrenal glands and by analysis of the homogeneous dinucleoside polyphosphates containing fractions with post-source-decay (PSD) matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS). The identity of the dinucleoside polyphosphates was confirmed by retention time comparison with authentic dinucleoside polyphosphates. Enzymatic analysis demonstrated an interconnection of the phosphate groups with the adenosines in the 5(')-positions of the riboses in all dinucleoside polyphosphates purified from adrenal glands. In conclusion, the identification of these dinucleoside polyphosphates in adrenal gland granules emphasises that these dinucleoside polyphosphates can be released from the adrenal glands upon stimulation into the circulation.

Caracterización de 46 mujeres ancianas con cáncer de mama / Characterization of 46 elderly women with breast cancer

El cáncer mamario en mujeres ancianas es frecuente, a menudo se diagnostica en estadios avanzados y su tratamiento motiva controversias. Entre 1980 y 1994 estudiamos retrospectivamente 46 mujeres con esta condición. La edad promedio fue de 78 años (rango 70 a 89 años). La detección fue realizada por la paciente en 39 (85 por ciento) casos y en 7 (15 por ciento) por examen médico. la estadificación correspondió en un (2,2 por ciento) caso estadio I, 18 (39,1 por ciento) a II, 23 (50 por ciento) a III, y 4 (8,7 por ciento) a IV. El tamaño promedio clínico del tumor primario fue de 5,5 cm y el histopatológico de 4,95 cm. Se realizó cirugía conservadora en 3 (6,1 por ciento) casos, mastectomía radical modificada en 9 (18,4 por ciento), mastectomía simple extendida en 18 (36,7 por ciento), mastectomía simple en 10 (20,4 por ciento) mastectomía de aseo en 5 (10,2 por ciento), y no se operaron 4 (8.2 por ciento) casos. En 32 pacientes se practicó disección axilar encontrando metástasis nodales en 16 (50 por ciento). El tipo histológico más frecuente fue carcinoma ductal en 35 (71,4 por ciento) casos; de éstos el grado histológico fue II en 21 (61,8 por ciento) y III en 7 (20,6 por ciento) y el grado nuclear fue 2 en 22 (64,7 por ciento) y 3 en 6 (17,6 por ciento). El seguimiento promedio de la serie fue de 58 meses (margen 2 a 204 meses). Al cierre de esta revisión 11 (23,9 por ciento) pacientes están vivas sin enfermedad, 30 (65,2 por ciento) fallecieron (13 (43,3 por ciento) por su cáncer mamario, 10 (33,3 por ciento) por otras causas, 7 (23,3 por ciento) por causa desconocida) y en 5 (10,9 por ciento) se ignora su estado

Genotyping of Plasmodium falciparum infections by PCR: a comparative multicentre study.

Genetic diversity of malaria parasites represents a major issue in understanding several aspects of malaria infection and disease. Genotyping of Plasmodium falciparum infections with polymerase chain reaction (PCR)-based methods has therefore been introduced in epidemiological studies. Polymorphic regions of the msp1, msp2 and glurp genes are the most frequently used markers for genotyping, but methods may differ. A multicentre study was therefore conducted to evaluate the comparability of results from different laboratories when the same samples were analysed. Analyses of laboratory-cloned lines revealed high specificity but varying sensitivity. Detection of low-density clones was hampered in multiclonal infections. Analyses of isolates from Tanzania and Papua New Guinea revealed similar positivity rates with the same allelic types identified. The number of alleles detected per isolate, however, varied systematically between the laboratories especially at high parasite densities. When the analyses were repeated within the laboratories, high agreement was found in getting positive or negative results but with a random variation in the number of alleles detected. The msp2 locus appeared to be the most informative single marker for analyses of multiplicity of infection. Genotyping by PCR is a powerful tool for studies on genetic diversity of P. falciparum but this study has revealed limitations in comparing results on multiplicity of infection derived from different laboratories and emphasizes the need for highly standardized laboratory protocols.

Linkage of prostate cancer susceptibility loci to chromosome 1.

Three prostate cancer susceptibility genes have been reported to be linked to different regions on chromosome 1: HPC1 at 1q24-25, PCAP at 1q42-43, and CAPB at 1p36. Replication studies analyzing each of these regions have yielded inconsistent results. To evaluate linkage across this chromosome systematically, we performed multipoint linkage analyses with 50 microsatellite markers spanning chromosome 1 in 159 hereditary prostate cancer families (HPC), including 79 families analyzed in the original report describing HPC1 linkage. The highest lod scores for the complete dataset of 159 families were observed at 1q24-25 at which the parametric lod score assuming heterogeneity (hlod) was 2.54 (P=0.0006) with an allele sharing lod of 2.34 (P=0.001) at marker D1S413, although only weak evidence was observed in the 80 families not previously analyzed for this region (hlod=0.44, P=0.14, and allele sharing lod=0.67, P=0.08). In the complete data set, the evidence for linkage across this region was very broad, with allele sharing lod scores greater than 0.5 extending approximately 100 cM from 1p13 to 1q32, possibly indicating the presence of multiple susceptibility genes. Elsewhere on chromosome 1, some evidence of linkage was observed at 1q42-43, with a peak allele sharing lod of 0.56 (P=0.11) and hlod of 0.24 (P=0.25) at D1S235. For analysis of the CAPB locus at 1p36, we focused on six HPC families in our collection with a history of primary brain cancer; four of these families had positive linkage results at 1p36, with a peak allele sharing lod of 0.61 (P=0.09) and hlod of 0.39 (P=0.16) at D1S407 in all six families. These results are consistent with the heterogeneous nature of hereditary prostate cancer, and the existence of multiple loci on chromosome 1 for this disease.

Regulation of sensorimotor gating in rats by hippocampal NMDA: anatomical localization.

Prepulse inhibition (PPI) of the startle reflex is a measure of sensorimotor gating that is reduced in humans with certain neuropsychiatric disorders, including schizophrenia, and in rats after manipulations of limbic cortico-striato-pallido-pontine circuitry. We have reported that PPI is reduced after specific manipulations of the hippocampal complex (HPC) in rats, but the mechanisms for these effects remain poorly understood. For example, dopaminergic substrates clearly regulate PPI, but the PPI-disruptive effects of intra-HPC carbachol or NMDA are not reversed by D2 receptor antagonists. This study examined the anatomical specificity within the hippocampal complex of the PPI-disruptive effects of NMDA infusion. Startle magnitude and PPI were assessed after acute bilateral infusion of NMDA (0, 0.4 or 0.8 microg) into the dorsal subiculum (DS), region CA1, the ventral subiculum (VS), the rostral entorhinal cortex (ECr) and the caudal entorhinal cortex (ECc). A dorsal-ventral gradient for NMDA effects was observed, with a dose-dependent disruption of PPI after NMDA infusion into the VS or EC, but not the DS, and with intermediate level effects observed after NMDA infusion into CA1. A second set of studies confirmed that the failure of NMDA effects in the DS did not reflect site-related differences in startle magnitude or baseline levels of PPI. These findings demonstrate the importance of the ventral, but not the dorsal HPC, in the glutamatergic regulation of PPI.

Dinucleotides as growth-promoting extracellular mediators. Presence of dinucleoside diphosphates Ap2A, Ap2G, and Gp2G in releasable granules of platelets.

Dinucleoside diphosphates, Ap(2)A, Ap(2)G, and Gp(2)G represent a new class of growth-promoting extracellular mediators, which are released from granules after activation of platelets. The presence of theses substances was shown after purification from a platelet concentrate. The substances were identified by UV spectrometry, retention time comparison with authentic substances, matrix-assisted laser desorption/ionization mass spectrometry, post-source-decay matrix-assisted laser desorption/ionization mass spectrometry, and enzymatic analysis. Ap(2)A, Ap(2)G, and Gp(2)G have growth-stimulating effects on vascular smooth muscle cells in nanomolar concentrations as shown by [(3)H]thymidine incorporation measurements. The calculated EC(50) (log m; mean +/- S.E.) values were -6.07 +/- 0.14 for Ap(2)A, -6.27 +/- 0.25 for Ap(2)G, and -6.91 +/- 0.44 for Gp(2)G. At least 61.5 +/- 4.3% of the dinucleoside polyphosphates are released by platelet activation. The intraplatelet concentrations suggest that, in the close environment of a platelet thrombus, similar dinucleoside polyphosphate concentrations can be found as in platelets. Intraplatelet concentration can be estimated in the range of 1/20 to 1/100 of the concentration of ATP. In conclusion, Ap(2)A, Ap(2)G, and Gp(2)G derived from releasable granules of human platelets may play a regulatory role in vascular smooth muscle growth as growth-promoting mediators.