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1.
Ann Cardiol Angeiol (Paris) ; 58(1): 20-6, 2009 Feb.
Article in French | MEDLINE | ID: mdl-18656847

ABSTRACT

Postural orthostatic tachycardia syndrome (POTS) is an inadequately understood pathology because its diagnosis is not based on the conventional methods of investigation. The orthostatic test allows to make the diagnosis easily. The objective of this study is to determine cardiovascular autonomic reflexes of 70 patients having POTS. The tests of exploration of the autonomic nervous system practised are: deep breathing, hand grip, mental stress and orthostatic test. The analysis of orthostatic test showed that the increase of the cardiac frequency, relative to the state of "beta" peripheral sympathetic hyperactivity occurred before the 2nd minute in 80% of patients. The POTS was considered "florid" in 43% of patients and had complicated of a rough and severe fall of systolic blood pressure inferior to 70 mmHg in four patients, after the fifth minute of the test. The analysis of the different tests had shown vagal hyperactivity in 63% of patients on deep breathing, in 93% of patients on hand grip and in 100% on orthostatic test. The "alpha" central sympathetic activity was increased in 76% of the cases and "beta" central sympathetic activity was high in 83% of cases. The "alpha" peripheral hyperactivity was observed in 63% of patients on hand grip, and in 44% on orthostatic test. The analysis of cardiovascular autonomic reflexes in patients affected by POTS allowing the determination of their autonomic profile, will contribute probably to a better understanding of this pathology and to a better orientation of its care.


Subject(s)
Hypotension, Orthostatic/physiopathology , Postural Orthostatic Tachycardia Syndrome/diagnosis , Postural Orthostatic Tachycardia Syndrome/physiopathology , Sympathetic Nervous System/physiopathology , Vagus Nerve/physiopathology , Adolescent , Adult , Aged , Electrocardiography , Female , Humans , Male , Middle Aged , Respiratory Mechanics , Retrospective Studies , Stress, Physiological , Syncope/physiopathology , Tachycardia/physiopathology , Tilt-Table Test
2.
Ann Cardiol Angeiol (Paris) ; 58(3): 139-43, 2009 Jun.
Article in French | MEDLINE | ID: mdl-18678361

ABSTRACT

UNLABELLED: High blood pressure (BP) is a major cause of cardiovascular disease and primary hypertension is a frequent pathological condition. Sympathetic hyperactivity may be involved in primary hypertension. The purpose of this study was mainly to evaluate sympathetic activity when performing cardiovascular autonomic profile examination in patients with primary hypertension in comparison with normotensive subjects. PATIENTS AND METHODS: This prospective study included one group of hypertensive patients (n=120, mean age 54 years) compared with a control group (n=120, mean age 52 years) of normotensive subjects. Autonomic tests included deep-breathing (DB), hand-grip (HG) and echostress test (ES). Comparison tests between the two groups, similar in age, were expressed as mean+/-SE and made using the t Student test, p<0.05 was considered significant. RESULTS: Alpha-adrenergic sympathetic response using ES method produced a BP response of 20,0%+/-9,8 in hypertensive patients group and 15,2%+/-8,6 in the control group (p<0.001). Alpha-adrenergic sympathetic response using three minutes HG test was of 16,7%+/-7,5 in hypertensive patients group and 13,3%+/-6,5 in the control group (p<0.001). Vagal stimulation in hypertensive group after DB showed that electrocardiographic: ECG (EKG) waves R (RR) interval variation was of 30,2%+/-8,1 meanwhile in the control group this RR variation was of 46,1%+/-21,1 p<0.001, and the one of HG of 15 seconds was 17,6%+/-10,2 versus 32,5%+/-12,7 p<0.001. CONCLUSION: Hypertensive patients had a significantly higher sympathetic response to central and peripheral stimulations and a significantly lower parasympathetic response when compared to normotensive controls.


Subject(s)
Hypertension/physiopathology , Sympathetic Nervous System/physiopathology , Adult , Aged , Female , Humans , Male , Middle Aged , Prospective Studies
3.
Neurophysiol Clin ; 37(1): 41-6, 2007.
Article in French | MEDLINE | ID: mdl-17418357

ABSTRACT

OBJECTIVE: The Deep-Breathing (DB) test is of major importance in the evaluation of the vagal response (VR). We applied this test to assess the VR in a group of subjects with functional (neurological, cardiovascular or digestive) symptoms unexplained by standard cardiac examination and to compare it with the VR measured in a group of healthy controls. PATIENTS AND METHODS: The following groups were considered: a C-Group of healthy controls (n=50), and three groups each consisting of 50 symptomatic patients (S1, S2, S3). Subjects in the S1-Group had a postural orthostatic tachycardia syndrome (POTS), while members of the S2-Group had arterial hypertension, and members of S3-Group had neither POTS nor arterial hypertension. The VR was expressed as a percentage variation of RR intervals 100x[(RR(max)-RR(min))/RR(min)], and was correlated with age and sex in the C-Group before any comparison. RESULTS: In controls the VR was 31.0%+/-8.2. It was negatively correlated with age (r=-0.42, p=0.003) and there was no significant difference between males (31.2%+/-5.7) and females (30.9%+/-9.0) (p=0.12). Compared to the C-Group, the VR was 51.6%+/-20.4 in the S1-Group (p<0.001), 26.9%+/-11.3 in the S2-Group (p<0.001), and 47.2%+/-22.7 in the S3-Group (p<0.001). CONCLUSION: The VR was independent of sex but was negatively correlated with age. In comparison with healthy controls, it was significantly increased in the patients with POTS and significantly decreased in hypertensives.


Subject(s)
Respiratory Mechanics/physiology , Vagus Nerve/physiology , Adult , Aged , Arteries/physiology , Blood Pressure/physiology , Female , Functional Residual Capacity/physiology , Humans , Male , Middle Aged , Posture/physiology , Tachycardia/diagnosis
4.
Oncogene ; 25(12): 1696-708, 2006 Mar 16.
Article in English | MEDLINE | ID: mdl-16449977

ABSTRACT

CD44 is a multifunctional protein involved in cell adhesion and signaling. The role of CD44 in prostate cancer (PCa) development and progression is controversial with studies showing both tumor-promoting and tumor-inhibiting effects. Most of these studies have used bulk-cultured PCa cells or PCa tissues to carry out correlative or overexpression experiments. The key experiment using prospectively purified cells has not been carried out. Here we use FACS to obtain homogeneous CD44(+) and CD44(-) tumor cell populations from multiple PCa cell cultures as well as four xenograft tumors to compare their in vitro and in vivo tumor-associated properties. Our results reveal that the CD44(+) PCa cells are more proliferative, clonogenic, tumorigenic, and metastatic than the isogenic CD44(-) PCa cells. Subsequent molecular studies demonstrate that the CD44(+) PCa cells possess certain intrinsic properties of progenitor cells. First, BrdU pulse-chase experiments reveal that CD44(+) cells colocalize with a population of intermediate label-retaining cells. Second, CD44(+) PCa cells express higher mRNA levels of several 'stemness' genes including Oct-3/4, Bmi, beta-catenin, and SMO. Third, CD44(+) PCa cells can generate CD44(-) cells in vitro and in vivo. Fourth, CD44(+) PCa cells, which are AR(-), can differentiate into AR(+) tumor cells. Finally, a very small percentage of CD44(+) PCa cells appear to undergo asymmetric cell division in clonal analyses. Altogether, our results suggest that the CD44(+) PCa cell population is enriched in tumorigenic and metastatic progenitor cells.


Subject(s)
Cell Line, Tumor/pathology , Hyaluronan Receptors/metabolism , Neoplasm Metastasis/pathology , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Stem Cells/physiology , Animals , Cell Line, Tumor/cytology , Cell Proliferation , Flow Cytometry , Humans , Male , Neoplasm Transplantation , Transplantation, Heterologous
5.
Neurophysiol Clin ; 35(4): 127-34, 2005 Oct.
Article in French | MEDLINE | ID: mdl-16311208

ABSTRACT

OBJECT: Dysfunction of autonomic nervous system (ANS) is implicated in the genesis and persistence of migraine. The objective of this study was to compare autonomic nervous system (ANS) profile of migraineurs during headache-free periods to a group of normal subjects based on cardio-vascular reactivity. METHODS: Patients with migraine according to the criteria of IHS 2004 were selected for the study. After a 30 min resting blood pressure (BP), the following standard tests were performed: deep-breathing (DB), hand grip (HG) of 15 s and 3 min, valsalva maneuver, echo stress, (ES) and tilt test (TT). Results were compared to 44 normal subjects, age similar, 37 female, (84.1%) using the Student test, with P < 0.005 as significant. RESULTS: Thirty-two patients (27 female (84.38%), 16-51 years, mean 40.41 +/- 7.8) were studied. Twenty-two patients (69%) had systolic blood pressure below 94 mmHg and 25 patients (78%) had diastolic blood pressure below 60 mmHg. Compared to normal, migraineurs exhibited a significantly higher vagal response (P < 0.001) and a significantly lower alpha sympathetic response, central by using ES as well as peripheral by using HG of 3 min (P < 0.001). CONCLUSIONS: Autonomic cardiovascular reactivity of patients with migraine showed a vagal hyperactivity and a deficiency of the alpha sympathetic system. This leads to further studies with new therapeutical approaches.


Subject(s)
Autonomic Nervous System/physiopathology , Migraine Disorders/physiopathology , Adolescent , Adult , Female , Humans , Male , Middle Aged
6.
Conf Proc IEEE Eng Med Biol Soc ; 2004: 5292-5, 2004.
Article in English | MEDLINE | ID: mdl-17271535

ABSTRACT

Molecular characterization of cancer could have important clinical benefits such as earlier cancer detection based on molecular characterization, the ability to predict the risk of cancer progression, real time margin detection, the ability to rationally select molecular therapy and to monitor response to the therapy. We present a new class of molecular specific contrast agents for optical imaging of carcinogenesis in vivo - gold nanoparticles conjugated with monoclonal antibodies specific for cancer biomarkers.

7.
Lasers Surg Med ; 29(1): 1-10, 2001.
Article in English | MEDLINE | ID: mdl-11500855

ABSTRACT

BACKGROUND AND OBJECTIVE: The hamster cheek pouch carcinogenesis model, using chronic treatments of dimethylbenz[alpha]anthracene (DMBA) was used as a model system to investigate changes in epithelial tissue autofluorescence throughout the dysplasia-carcinoma sequence. STUDY DESIGN/MATERIALS AND METHODS: Fluorescence emission spectra were measured weekly from 42 DMBA-treated animals and 20 control animals at 337, 380, and 460 nm excitation. A subset of data in which histopathology was available was used to develop diagnostic algorithms to separate neoplastic and non-neoplastic tissue. The change in fluorescence intensity over time was examined in all samples at excitation-emission wavelength pairs identified as diagnostically useful. RESULTS: Algorithms based on autofluorescence can separate neoplastic and non-neoplastic tissue with 95% sensitivity and 93% specificity. Greatest contributions to diagnostic algorithms are obtained at 380 nm excitation, and 430, 470, and 600 nm emission. Changes in fluorescence intensity are apparent as early as 3 weeks after initial treatment with DMBA, whereas morphologic changes associated with dysplasia occur on average at 7.5-12.5 weeks after initial treatment. CONCLUSIONS: Fluorescence spectroscopy provides a potential tool to identify biochemical changes associated with dysplasia and hyperplasia, which precede morphologic changes observed in histologically stained sections.


Subject(s)
Carcinoma/pathology , Spectrometry, Fluorescence , 9,10-Dimethyl-1,2-benzanthracene , Algorithms , Animals , Carcinoma/chemically induced , Carcinoma/etiology , Cheek , Cricetinae , Epithelium , Time Factors
8.
Lab Anim ; 35(2): 157-62, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11315165

ABSTRACT

Sixteen DNA microsatellites or simple sequence length polymorphisms (SSLPs), generated by polymerase chain reaction (PCR) were selected for use in the genetic quality control of the nine inbred SENCAR strains currently available. The SENCAR strains constitute a powerful tool for mechanistic studies of multi-stage skin carcinogenesis, as well as for studies to understand the underlying genetic basis of resistance to tumour promotion and progression. SSLP analysis is a fast and economical way for detecting genetic contamination (unexpected outcrosses) among these closely-related albino strains, where standard immunological and biochemical markers have been shown to be insufficient.


Subject(s)
Mice, Inbred SENCAR/genetics , Microsatellite Repeats/genetics , Polymorphism, Genetic/genetics , Animals , DNA/chemistry , DNA/genetics , DNA/isolation & purification , Female , Genetic Markers/genetics , Mice , Mice, Inbred SENCAR/classification , Polymerase Chain Reaction/veterinary , Quality Control
9.
Semin Thorac Cardiovasc Surg ; 13(4): 417-30, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11807737

ABSTRACT

The healthy left ventricle, with remarkable mechanical efficiency, has a gothic architecture, which results from the disposition of the myocardial fibers supported and maintained by a normal collagen matrix scaffold. This conclusion, arising from the analysis of roman and gothic buildings and from comparative biology of the left ventricles of different species, has been substantiated by the study of three-dimensional images obtained by MRI and analyzed with mathematic methods for measurements of the curvature and thickness of the ventricular walls. The assessment of left ventricular functional reserve based on the architecture has been very important in making therapeutic and surgical decisions in our patients and has important implications for the design of surgical strategies designed to try to improve ventricular function by restoring an architecture that allows more efficient ventricular mechanics. The structural approach and its combination with important advances in the knowledge of membrane channels, signaling pathways, cytokines, growth factors, neuroregulation, and targeted pharmacology, and with the advances in methods for reducing hemodynamic load and its cellular and structural consequences, is certain to bring about a dramatic change in the very serious and highly prevalent congestive failure associated with the Romanesque transformation of the diseased left ventricle.


Subject(s)
Architecture , Cardiology , Heart Ventricles/anatomy & histology , Heart/anatomy & histology , Heart/physiology , Animals , Heart Failure/physiopathology , Humans , Image Processing, Computer-Assisted , Microscopy, Electron, Scanning , Myocardium/ultrastructure , Ventricular Function
10.
Child Welfare ; 79(5): 499-515, 2000.
Article in English | MEDLINE | ID: mdl-11021344

ABSTRACT

Administrative databases hold the potential to have a significant impact on the development of effective child welfare programs and policies. This article discusses the strengths and weaknesses of administrative databases, issues with their implementation and data analysis, and effective presentation of their data at different levels in child welfare organizations.


Subject(s)
Child Welfare , Databases as Topic/statistics & numerical data , Decision Support Systems, Management , Organizational Innovation , Social Work/organization & administration , Administrative Personnel , Child , Data Collection , Decision Making, Organizational , Government Programs/organization & administration , Humans , Models, Organizational , Outcome Assessment, Health Care , Policy Making , Private Sector/organization & administration , United States
11.
Mol Carcinog ; 28(4): 191-5, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10972988

ABSTRACT

The two-stage model, initiation with 7,12-dimethylbenz[a]anthracene and promotion with 12-O-tetradecanoylphorbol-13-acetate, of mouse skin carcinogenesis has been the protocol of choice to study the genetic susceptibility to carcinogens, the outbred SENCAR mouse being the most widely used skin tumor-sensitive animal model. Squamous cell carcinomas (SCCs) develop from many of the papillomas, making these mice a useful model for epithelial tumorigenesis and for the progression to malignant tumors. Nine different inbred strains derived from outbred SENCAR mice have been recently reported. Interestingly, these strains display different sensitivities to two-stage carcinogenesis, and, in particular, some of them show a dissociation between susceptibility to papilloma development and the malignant conversion of these into SCC. However, the utility of these SENCAR strains for genetic mapping is limited by the lack of information regarding DNA variant alleles among them. Therefore, we analyzed the nine inbred strains with microsatellite markers distributed along the 20 chromosomes and in this article report the variant alleles found. The information presented is likely to be helpful for linkage analysis and marker-assisted development of congenic strains between SENCAR-derived inbred strains.


Subject(s)
Genetic Variation , Mice, Inbred SENCAR/genetics , Microsatellite Repeats/genetics , 9,10-Dimethyl-1,2-benzanthracene , Animals , Genetic Markers , Genetic Predisposition to Disease , Genotype , Mice , Skin Neoplasms/chemically induced , Skin Neoplasms/genetics , Species Specificity , Tetradecanoylphorbol Acetate
12.
Carcinogenesis ; 21(4): 641-6, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10753198

ABSTRACT

The development and initial characterization of five new inbred strains of SENCAR mice are described in this paper. Ten randomly selected pairs of outbred SENCAR mice were mated and offspring from each separately maintained parental line were sib mated at each successive generation to result in inbred strains. Due to poor reproductive performance only five of the original 10 lines were bred to homogeneity. Initial characterization of the five remaining lines (referred to as SL2/sprd, SL5/sprd, SL7/sprd, SL8/sprd and SLl0/sprd) at F12 for their responsiveness to a two-stage carcinogenesis protocol (10 nmol 7,12-dimethylbenz[a]anthracene and 0.25 microg 12-O-tetradecanoylphorbol-13 acetate) revealed three groups of responders in terms of the number of papillomas per mouse: SL2/sprd and SL8/sprd > SL7/sprd and SL10/sprd >> SL5/sprd. The papilloma responses in SL2/sprd and SL8/sprd were very similar to SENCAR B/Pt compared at the same doses. Papillomas induced on SL2/sprd had the highest propensity to progress to squamous cell carcinomas, similar to that observed in outbred SENCAR and SENCAR B/Pt mice. More detailed comparison of the responsiveness of SL2/sprd and SL5/sprd at Fl5 showed that these two inbred strains differed in their sensitivity to TPA-induced epidermal hyperplasia and that the dose of TPA required to produce a tumor response in SL5/sprd in comparison with that in SL2/sprd was 4-20 times higher. Overall, the availability of the different inbred SENCAR strains will greatly aid mechanistic studies of multistage skin carcinogenesis as well as studies to understand the underlying genetic basis of resistance to tumor promotion and progression in this model system.


Subject(s)
Mice, Inbred SENCAR , Skin Neoplasms/chemically induced , 9,10-Dimethyl-1,2-benzanthracene , Animals , Carcinoma, Squamous Cell/chemically induced , Dose-Response Relationship, Drug , Mice , Papilloma/chemically induced , Tetradecanoylphorbol Acetate
13.
J Immunol ; 164(4): 1881-8, 2000 Feb 15.
Article in English | MEDLINE | ID: mdl-10657637

ABSTRACT

We previously reported that precursors within the keratin (K) 8+5+ thymic epithelial cell (TEC) subset generate the major cortical K8+5- TEC population in a process dependent on T lineage commitment. This report demonstrates that expression of a cyclin D1 transgene in K8+5+ TECs expands this subset and promotes TEC and thymocyte development. Cyclin D1 transgene expression is not sufficient to induce TEC differentiation in the absence of T lineage-committed thymocytes because TECs from both hCD3epsilon transgenic and hCD3epsilon/cyclin D1 double transgenic mice remain blocked at the K8+5+ maturation stage. However, enforced cyclin D1 expression does expand the developmental window during which K8+5+ cells can differentiate in response to normal hemopoietic precursors. Thus, enhancement of thymic function may be achieved by manipulating the growth and/or survival of TEC precursors within the K8+5+ subset.


Subject(s)
CD3 Complex , Cyclin D1/biosynthesis , Epithelial Cells/cytology , Gene Expression Regulation/immunology , T-Lymphocytes/cytology , Thymus Gland/cytology , Thymus Gland/metabolism , Transgenes , Animals , Cell Differentiation/genetics , Cell Differentiation/immunology , Cell Lineage/immunology , Cyclin D1/genetics , Epithelial Cells/immunology , Epithelial Cells/metabolism , Keratins/biosynthesis , Mice , Mice, Inbred C57BL , Mice, Transgenic , Receptors, Antigen, T-Cell/genetics , Stem Cells/metabolism , Thymus Gland/immunology
15.
Opt Express ; 7(12): 436-46, 2000 Dec 04.
Article in English | MEDLINE | ID: mdl-19407895

ABSTRACT

Using the hamster cheek pouch carcinogenesis model, we explore which fluorescence excitation wavelengths are useful for the detection of neoplasia. 42 hamsters were treated with DMBA to induce carcinogenesis, and 20 control animals were treated only with mineral oil. Fluorescence excitation emission matrices were measured from the cheek pouches of the hamsters weekly. Results showed increased fluorescence near 350-370 nm and 410 nm excitation and decreased fluorescence near 450-470 nm excitation with neoplasia. The optimal diagnostic excitation wavelengths identified using this model - 350-370 nm excitation and 400-450 nm excitation - are similar to those identified for detection of human oral cavity neoplasia.

16.
Oncogene ; 16(15): 1913-20, 1998 Apr 16.
Article in English | MEDLINE | ID: mdl-9591774

ABSTRACT

Deregulated expression of cyclin D1 has been found in several types of human tumors. In order to investigate factors involved in human prostate cancer progression, we studied the effects of cyclin D1 overexpression on human prostate cancer cell proliferation and tumorigenicity by transfecting LNCaP cells with a retroviral vector containing human cyclin D1 cDNA. When compared to the parental and control-vector transfected LNCaP cells, these cyclin D1-transfected cells had more cells in S-phase and lower growth factor requirements. Furthermore, these cells grew more in androgen-free medium. We also detected higher levels of Rb phosphorylation and E2F-1 protein levels in LNCaP/cyclin D1 cells than that in the parental and vector control cells in medium with or without androgen. Cyclin D1 transfected clones formed tumors more rapidly than control and parental cells. These tumors were refractory to the androgen-ablation treatment by castration, whereas tumors from parental and vector-control LNCaP cells regressed within 4 weeks after castration. These results suggest that overexpression of cyclin D1 changes the growth properties, increases tumorigenicity and decreases the requirement for androgen stimulation in LNCaP cells both in vitro and in vivo.


Subject(s)
Cyclin D1/physiology , Prostatic Neoplasms/pathology , Androgens/pharmacology , Animals , Cell Division , Cyclin D1/genetics , Humans , Male , Mice , Mice, Nude , Prostatic Neoplasms/etiology , RNA, Messenger/analysis , Tumor Cells, Cultured
17.
Carcinogenesis ; 19(1): 125-32, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9472703

ABSTRACT

The SENCAR stock of mice has proved to be a useful model in dissecting out the multistage nature as well as the critical mechanisms involved in skin tumorigenesis. This outbred stock was selectively bred to be susceptible to initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). In order to obtain mice more suitable for genetic analyses of tumor susceptibility and tissue transplantation studies, several inbred lines of mice were derived from the SENCAR stock. One of these lines, the SSIN mice, has a higher susceptibility to tumor promotion compared to the SENCAR stock but is very resistant to tumor progression. On the other hand, the SENCAR B/Pt mice, derived also from the outbred stock, not only have a tumor promotion susceptibility almost identical to the SSIN mice, but they also have a high susceptibility to tumor progression. In order to understand the nature of the phenotypic differences between these two inbred lines we have characterized them using several parameters and markers that are associated with the progression of papillomas to squamous cell carcinoma (SCC). In this sense we analysed the tumor multiplicity and SCC incidence, and the expression of markers of progression and cell cycle related proteins in papillomas derived from both strains. Our results showed that while both strains have a similar papilloma multiplicity and incidence the SENCAR B/Pt mice have 67% incidence of SCC, compared to 0% in the SSIN. SENCAR B/Pt papillomas at 30 weeks of promotion have a higher and aberrant expression of K13, and loss of connexin 26. TGF-beta1 was found to be over-expressed in the suprabasal and superficial cells in the SENCAR B/Pt papillomas, while it was only expressed in the superficial cell layer in those derived from SSIN. The SENCAR B/Pt papillomas also showed an enlarged proliferative compartment with overexpression of cyclin D1 and PCNA as seen by immunohistochemistry and Western blot.


Subject(s)
Papilloma/chemically induced , Papilloma/genetics , Skin Neoplasms/chemically induced , Skin Neoplasms/genetics , 9,10-Dimethyl-1,2-benzanthracene , Animals , Antigens, Surface/analysis , Biomarkers, Tumor/analysis , Carcinogens , Cyclin D1/analysis , Disease Susceptibility , Female , Immunohistochemistry , Integrin alpha6beta4 , Integrins/analysis , Mice , Mice, Inbred Strains , Papilloma/pathology , Proliferating Cell Nuclear Antigen/analysis , Skin Neoplasms/pathology , Tetradecanoylphorbol Acetate , Time Factors , Transforming Growth Factor beta/analysis
18.
Mol Carcinog ; 20(1): 125-36, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9328443

ABSTRACT

To directly compare the expression patterns of different proteins known to be altered during mouse skin carcinogenesis, serial sections of normal and hyperplastic skin and tumors from various stages of 7,12-dimethylbenz[a]anthracene-initiated, 12-O-tetradecanoylphorbol-13-acetate-promoted female SENCAR mice were examined by immunohistochemistry. In untreated, normal mouse skin, keratin 1 (K1) and transforming growth factor-beta1 (TGFbeta1) were strongly expressed in the suprabasal layers, whereas integrin alpha6beta4 was expressed only in basal cells and only moderate staining for transforming growth factor-alpha (TGFalpha) was seen. In hyperplastic skin, TGFalpha expression became stronger, whereas expression of another epidermal growth factor (EGF) receptor ligand, heparin-binding EGF-like growth factor (HB-EGF), was strongly induced in all epidermal layers from no expression in normal skin. Likewise, the gap-junctional protein connexin 26 (Cx26) became highly expressed in the differentiated granular layers of hyperplastic skin relative to undetectable expression in normal skin. Expression of cyclin D1 in the proliferative cell compartment was seen in all benign and malignant tumors but not in hyperplastic skin. Beginning with very early papillomas (after 10 wk of promotion), expression of alpha6beta4 in suprabasal cells and small, focal staining for keratin 13 (K13) were seen in some tumors. Later (after 20-30 wk), focal areas of gamma-glutamyl transpeptidase (GGT) activity appeared in a few papillomas, whereas TGFbeta1 expression began to decrease. Cx26 and TGFalpha staining became patchier in some late-stage papillomas (30-40 wk), whereas suprabasal alpha6beta4, K13, and GGT expression progressively increased and K1 expression decreased. Finally, in squamous cell carcinomas (SCCs), there was an almost complete loss of K1 and a further decline in TGFalpha, HB-EGF, TGFbeta1, and Cx26 expression. On the other hand, almost all SCCs showed suprabasal staining for alpha6beta4 and widespread cyclin D1 and K13 expression, whereas only about half showed positive focal staining for GGT activity.


Subject(s)
Neoplasm Proteins/biosynthesis , Skin Neoplasms/metabolism , Skin/metabolism , 9,10-Dimethyl-1,2-benzanthracene , Animals , Antigens, Surface/biosynthesis , Carcinogens , Connexin 26 , Connexins/biosynthesis , Cyclin D1 , Cyclins/biosynthesis , Epidermal Growth Factor/biosynthesis , Female , Heparin-binding EGF-like Growth Factor , Integrin alpha6beta4 , Integrins/biosynthesis , Intercellular Signaling Peptides and Proteins , Keratins/biosynthesis , Mice , Mice, Inbred SENCAR , Oncogene Proteins/biosynthesis , Skin/drug effects , Skin Neoplasms/chemically induced , Tetradecanoylphorbol Acetate , Transforming Growth Factor alpha/biosynthesis , gamma-Glutamyltransferase/biosynthesis
19.
Am J Cardiol ; 80(4): 434-41, 1997 Aug 15.
Article in English | MEDLINE | ID: mdl-9285654

ABSTRACT

Myocardial infarction (MI) is characterized by cellular necrosis which undergoes fibrotic transformation over time. Cine magnetic resonance imaging (MRI) offers high-resolution 3-dimensional images of the left ventricular myocardium, allowing sampling of the myocardial wall thickness over the entire left ventricle. Tomographic (single-photon emission computed tomography [SPECT]) thallium images also provide 3-dimensional information on the location and level of thallium uptake, which has been shown to correlate with myocardial viability. The purposes of this study were: (1) to examine the relation between both end-diastolic and end-systolic wall thickness and normalized thallium-201 uptake over the left ventricle in a group of patients with MI, (2) to examine the relation between regional wall thickening and normalized thallium uptake, and (3) to examine the relation between thallium uptake and wall thickness both early and late after infarction. Twenty-four patients with MI underwent stress, redistribution, and reinjection thallium SPECT imaging and cine MRI within several days. Seventeen patients underwent imaging late after infarction and 7 underwent imaging early after infarction. Normalized thallium activity was correlated with MRI wall thicknesses at both end-diastole and end-systole for 18 segments for each ventricle. In addition, end-diastolic and end-systolic wall thicknesses were grouped by their corresponding thallium activity levels into percentiles. End-systolic wall thickness correlated significantly with normalized thallium uptake in 14 of 18 segments, end-diastolic wall thickness in only 4 of 18 segments, and wall thickening in only 3 of 18 segments. Mean values for end-diastolic and end-systolic wall thicknesses corresponding to severely reduced (<50%) normalized thallium activity were 9.9 +/- 1.1 and 8.5 +/- 0.6, respectively. Using receiver-operating curve analysis, end-systolic wall performed as a better diagnostic parameter than end-diastolic wall for identifying severely reduced thallium activity levels. For all levels of thallium activity, end-diastolic wall thicknesses were all thinner late versus early after MI, whereas end-systolic wall thickness was thinner only in the segments corresponding to severely reduced thallium activity. Based on these results, end-systolic wall thickness is the best noninvasive anatomic parameter of myocardial scar.


Subject(s)
Heart Ventricles/diagnostic imaging , Heart Ventricles/pathology , Magnetic Resonance Imaging, Cine , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/pathology , Myocardium/metabolism , Myocardium/pathology , Thallium Radioisotopes/metabolism , Tomography, Emission-Computed, Single-Photon , Adult , Confounding Factors, Epidemiologic , Female , Heart Ventricles/metabolism , Humans , Male , Middle Aged , Myocardial Infarction/metabolism , ROC Curve
20.
Lab Invest ; 75(3): 339-48, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8804357

ABSTRACT

By serving as host recipients of xenografts from both humans and animals, severe combined immunodeficient (SCID) mice have become valuable to many laboratories interested in examining the pathophysiology of different diseases. To gain insight into the usefulness of the SCID mutation in retrovirus research, rhesus monkey fetal hematolymphoid tissues (liver and thymus) were used to construct a SCID-rhesus chimeric mouse (SCID-rh) and were engrafted in the renal capsule. The size and maturation of the thymic engrafts were monitored grossly, histologically, and immunologically. SCID mice were tolerant to rhesus tissues, and thymic engrafts contained thymocytes at different stages of maturation and differentiation that had morphologic features similar to age-matched rhesus thymus. Mature single positive CD2+, CD4+, and CD8+ T lymphocytes that were phenotypically similar to rhesus T lymphocytes were present at low levels (2% to 5%) in the peripheral blood and at moderately higher levels (7% to 15%) in the spleens of SCID-rh mice obtained between 12 and 15 weeks after thymus/liver engraftment. Within 3 weeks after engraftment, > 85% of the thymocytes in the thymic engrafts were immature double positive CD4+CD8+ T cells. The highest number of positive cells were seen in thymic engrafts obtained at 12 to 18 weeks. During these weeks, > 90% of the cells were double positive (CD2+CD4+, CD2+CD8+, and CD4+CD8+). After infection of the engrafted thymus tissue with simian immonodeficiency virus (SIVmac239), PCR analysis revealed successful viral infection of engrafts at 2 and 4 weeks after infection. No significant histopathologic and flow cytometric changes were observed in the thymic engrafts at 2 and 4 weeks after infection. An unrelated lesion of thymic lymphomas involving the SCID host thymus was seen in 12% of the mice. The data presented herein suggest that the SCID-rh is a valuable model for specific studies related to thymus-retrovirus interaction and that it could be used for further studies. The results are discussed in relation to current knowledge of thymus involvement during simian and human immunodeficiency virus infection.


Subject(s)
Fetal Tissue Transplantation , Immune Tolerance , Liver/embryology , Simian Acquired Immunodeficiency Syndrome/pathology , Thymus Gland/embryology , Thymus Gland/immunology , Transplantation, Heterologous , Animals , Liver/pathology , Lymphatic Diseases/virology , Macaca mulatta , Male , Mice , Mice, SCID , Thymus Gland/pathology
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