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J S Norris

Publications and source records attributed to J S Norris.

At least 37 records · Page 2Linked to original sources
PubMed1999

Exogenous 17beta-estradiol blocks alpha and mu but not pi class glutathione S-transferase immunoreactivity in epithelium of Syrian hamster vas deferens.

Members of the glutathione S-transferase (GST) family of detoxification enzymes play a role in chemotherapy resistance in certain cancers but have not been directly implicated as agents whose absence may predispose tissues to hormonally induced tumorigenesis. Here we report the development of a polyclonal antiserum to a hamster mu class GST, and immunohistochemical analysis of alpha, mu, and pi class GSTs to study the effects of hormone treatment on their expression in reproductive tract tissues of male golden Syrian hamsters. These animals develop leiomyosarcomas in the vas deferens after treatment with testosterone propionate (TP) and 17beta-estradiol (E2). High levels of all three GST classes were detected throughout the reproductive tract epithelium of control animals. In 100% of the experimental animals, 4 weeks of treatment either with E2 alone, or with E2 plus TP promoted a complete loss of immunostaining for alpha and mu class GSTs, but not for pi class GSTs, only in the epithelial lining of the vas deferens. In contrast, treatment with TP alone resulted in moderate hyperplasia of smooth muscle in the proximal vas deferens, with no cellular atypia and no changes in immunoreactivity of any of the GST classes. The consistent and site-specific nature of these results strongly suggests a functional role for GSTs in hormonally induced carcinogenic process. (J Histochem Cytochem 47:91-98, 1999)

Animals↗
PubMed1999

A simple relationship between radiological arteriovenous malformation hemodynamics and clinical presentation: a prospective, blinded analysis of 31 cases.

OBJECT: The authors sought to establish prospectively whether there is a simple relationship between radiological features of brain arteriovenous malformation (AVM) hemodynamics and a patient's clinical presentation. METHODS: Thirty-one consecutive patients with AVMs underwent cerebral angiography at 3.8 frames/second during each standardized injection of contrast material. Contrast dilution curves were derived from the image sequences by using regions of interest (ROIs) traced on arteries feeding and veins draining the AVM nidus. Angiographic parameters were then analyzed in a blinded fashion. These parameters included the times required to reach the peak contrast density, the contrast decay time, and fractions thereof, in the ROI for each vessel. The authors determined whether these parameters, the arteriovenous transit time, and/or AVM size were related to patients' presentation with hemorrhage (11 patients), seizure (11 patients), or other clinical symptoms (nine patients). Statistically significant results were found only in analyses of arterial phase times to reach peak contrast density. Analyses of venous parameters, AVM size, and nidus transit time showed trends but no statistical significance. Arterial filling with contrast material was significantly slower in patients presenting with hemorrhage (mean 50%, 80%, and 100% of time to peak +/- standard error [SE] = 1.19+/-0.13, 1.97+/-0.18, and 3.04+/-0.34 seconds, respectively) compared with patients presenting with seizures (mean 50%, 80%, and 100% of time to peak +/- SE = 0.80+/-0.12, 1.32+/-0.18, and 1.95+/-0.29 seconds, respectively) according to analysis of variance (p<0.05) and post-hoc t-tests (p<0.05) for each parameter. Patients who presented with other symptoms had intermediate arterial filling times. CONCLUSIONS: These simple hemodynamic parameters, which can be obtained without added risk to the patient, may help identify a subset of individuals in whom AVMs pose a higher risk of future hemorrhage and who may therefore warrant more expeditious treatment.

Adult↗
PubMed1998

Glutathione S-transferase in hormonal carcinogenesis.

Treatment with testosterone propionate (TP) and diethylstilbestrol (DES) or TP and estradiol (E2) for 8-9 months causes development of leiomyosarcomas in the vas deferens or uterus of Golden Syrian hamsters at a frequency of 100%. In males, treatment with estrogens alone results in renal tumors, fatal within 6 months. No leiomyosarcomas have been detected after treatment with estrogens alone, perhaps due to this high mortality rate. In tissue culture, treatment with the glucocorticoid (GC) triamcinolone acetonide (TA) results in an increased expression of a mu-class glutathione S-transferase (GST) (hGSTYBX). We have characterized this induction as a secondary response, i.e. requiring new protein synthesis. Here we describe homologies to known transcription factor-binding sites in the hGSTYBX promoter which may be involved in the induction event. hGSTYBX is a member of a superfamily of detoxification enzymes, induced by genotoxic compounds and reactive oxygen species (ROS). We also describe the effects of several known inducers of other GST family members on hGSTYBX. While implicated in many chemotherapeutic-resistant tumors, GST enzymes have not yet been characterized as a functional agent in hormonal carcinogenesis. This latter possibility is the focus of our investigations. To study the effects of hormone treatment on GST levels in vivo, we have developed a polyclonal antibody to hGSTYBX, and conducted immunohistochemistry on tissues from control and treated animals. Treatment with TP and E2 causes a loss of hGSTYBX expression in the epithelium of the vas deferens. We hypothesize that the loss of this protective enzyme leaves the cells vulnerable to the genotoxic effects of estrogen or estrogenic metabolites.

Animals↗
PubMed1998

Thrombospondin 1 is expressed by mesenchymal cells in mouse post-natal skin and hair follicle development.

Thrombospondin 1 is an extracellular matrix glycoprotein with multiple functions. In the skin, it has been immunolocalized to basement membrane, and its expression increases during embryogenesis and wound healing. Its normal cellular source in the skin is not known, except during wound healing, where macrophages and keratinocytes seem to be the primary source. We have analysed the expression of thrombospondin 1 mRNA in normal mouse skin at different ages by in situ hybridization. It was found that the mRNA is expressed by dermal mesenchymal cells and mature fibroblasts and developmentally regulated during post-natal skin growth and morphogenesis. In adult mouse skin, expression of the thrombospondin is restricted to the mesenchymal cells of hair follicle papilla. These results suggest that the regulation of thrombospondin 1 transcription in mesenchymal cells can play an important role in post-natal skin development. Its mRNA expression is a characteristic of adult dermal papilla cells with a potential role in hair development.

Aging↗
PubMed1998

Primary transsphenoidal microsurgery in the treatment of craniopharyngiomas.

Thirty craniopharyngiomas were operated on between 1983 and 1993. Eight patients underwent surgery solely via the transsphenoidal route. None of these had undergone surgery previously. The eight patients were followed up for a period of 120 months (mean 87.5 months). The tumour was removed totally in five and subtotally in three patients. All eight patients had one or more endocrine abnormalities prior to surgery. Five patients presented with visual field defects or decreased visual acuity, which improved postoperatively in all cases. Seven received radiotherapy, with one declining this treatment. No recurrences have occurred during follow-up in any of the group. Primary transsphenoidal surgery is a both safe and effective treatment for those craniopharyngiomas that are located within an enlarged sella, have no calcification and are not adherent to parasellar structures.

Adrenocorticotropic Hormone↗
PubMed1998

Novel retroviral sequences are expressed in the epididymis and uterus of Syrian hamsters.

Combined androgen and oestrogen treatment of male or female Syrian hamsters results via an unknown mechanism in the formation of leiomyosarcomas in the reproductive tract. We have examined the possibility that retroviral gene expression may play a role in tumorigenesis. Evidence of virus-like particles in epididymis and seminal fluid is shown in electron micrographs. We identified expressed retroviral sequences by using RT-PCR to amplify a conserved retroviral reverse transcriptase coding region in RNA isolated from epididymis, testis, clarified seminal fluid and uterus. Phylogenetic analysis allowed us to classify the sequences into two distinct groups: (1) mammalian type-C viruses, having similarity to Moloney murine leukaemia virus, feline leukaemia virus and gibbon ape leukaemia virus amongst others; (2) a mixed ABCD group containing, for example, Chinese hamster and murine intracisternal A-particle virus sequences, mouse mammary tumour virus and human and simian retroviral sequences. The presence of putative full-length retrovirus related to mammalian type-C viruses in the epididymis and uterus was confirmed by Northern blot analysis. However, steroid treatment did not alter retroviral RNA levels in the epididymis or in a uterine tumour relative to untreated uterus. In summary, Syrian hamster reproductive tissues were found to express unique retroviral sequences; however, their role, if any, in hormonal carcinogenesis remains unresolved.

Amino Acid Sequence↗
PubMed1998

Pediatric intracranial aneurysms.

Pediatric intracranial aneurysms are uncommon. There are several differences between childhood and adult aneurysms, but the evaluation and management of childhood aneurysms is similar to that in adults. This article will review the incidence, pathology, clinical features, management, and expected outcome of childhood aneurysms.

Adolescent↗
PubMed1997

Glutathione S-transferase Yc cDNA from Syrian hamster kidney.

A cDNA encoding alpha-class glutathione S-transferase Yc (GSTYc) has been isolated from a Syrian hamster kidney library, and its nucleotide sequence (968 bp) has been determined. Analysis of the deduced amino acid sequence revealed a high level of identity between Syrian hamster GSTYc, rat GST Yc1 and Yc2 and mouse GSTYc. Northern-blot experiments demonstrated that Syrian hamster GSTYc expression is tissue-specific. A GSTYc mRNA of approx. 1 kb is expressed in liver, kidney, vas deferens and epididymis. Expression of the GSTYc transcript was not detected in testis or uterus.

Amino Acid Sequence↗
PubMed1997

Molecular cloning of TA16, a transcriptional repressor that may mediate glucocorticoid-induced growth arrest of leiomyosarcoma cells.

The DDT1 MF2 smooth muscle tumor cell line was derived from an estrogen/androgen-induced leiomyosarcoma that arose in the ductus deferens of a Syrian hamster. The growth of this cell line is arrested at the G0/G1 phase of the cell cycle after treatment with glucocorticoids. To identify the putative gene(s) that are potentially involved in this hormone-induced cell growth arrest, we have used a differential screening technique to clone those genes whose expression is induced or up-regulated by glucocorticoids. A number of glucocorticoid response genes were thereby isolated from the leiomyosarcoma cells. One of these clones, termed TA16, was found to be markedly up-regulated by glucocorticoids in DDT1 MF2 cells, but only marginally changed in GR1 cells, a glucocorticoid-resistant variant that was selected from the wild type DDT1 MF2 cell. Isolation and sequencing of its intact cDNA indicated that the TA16 encodes a protein 485 amino acids long, and its sequence is closely homologous to a novel transcriptional repressor that presumably represses the transcription activity of some zinc finger transcriptional factors through a direct interaction. Transfection assays demonstrated that introduction of an antisense TA16 cDNA expression vector, controlled by an MMTV promoter, into the DDT1 MF2 cell significantly relieved the glucocorticoid-induced cell growth arrest. This finding suggests that TA16 might participate in the mediation of glucocorticoid-induced cell cycle arrest in leiomyosarcoma cells.

Amino Acid Sequence↗
PubMed1997

Prospective study of zero drift in fiberoptic pressure monitors used in clinical practice.

One hundred and one fiberoptic pressure transducers (59 subdural and 42 ventricular) were studied in 86 patients (some in whom more than one device had been inserted). Only four complications occurred: two transient cerebrospinal fluid leaks after removal and two clinically insignificant intracerebral hematomas. No intracranial infections could be attributed to the devices. Technical problems occurred 23 times, with 11 devices ceasing to function before removal, seven becoming displaced, and five microventricular catheters failing to enter the ventricles. Zero-drift readings were obtained for 83 devices at the time of removal (median 66 hours after insertion, range 2 hours-13 days). There was a clear negative bias in the readings (median -3), with a wide range of values (-12 to +14 mm Hg; interquartile range -6 to -1) that was apparent even in the first 3 days of use. There was no important relationship between zero drift and any recorded variable. It is concluded that zero drift of fiberoptic pressure transducers is a significant problem and that undue reliance should not be placed on intracranial pressure readings from these devices in isolation from other clinical and radiological information.

Equipment Failure↗
PubMed1996

Ontogenic and glucocorticoid-accelerated expression of rat 14 kDa bile acid-binding protein.

BACKGROUND: A 14 kDa protein is a major rat ileal cytosolic bile acid-binding protein (14 kDa I-BABP). This report describes the normal and glucocorticoid-accelerated postnatal expression of 14 kDa I-BABP. METHODS. 14 kDa I-BABP and its mRNA were detected by antiserum and antisense cRNA probe, respectively, in ileum and ovary from 7-, 14-, 21-, 28-, and 35-day-old rats. RESULTS: A positive histochemical reaction with 14 kDa I-BABP antiserum was found in cytosol of ileal enterocytes and ovarian luteal cells at 21 and 35 days of age, respectively. Likewise, Northern blot analysis indicated that the cRNA probe hybridized to a single transcript of 500 bp in total cellular RNA prepared from the ileum of 21-day-old and ovary of 35-day-old rats. Corticosteroid treatment resulted in a histochemical reaction in ileum of 14-day-old animals as compared to the appearance of this reaction in 21-day-old control littermates. Similarly, Northern blot analysis detected the earlier appearance of mRNA levels in corticosteroid-treated animals (11 days vs. 17 days in control animals). CONCLUSIONS: 14 kDa I-BABP and its mRNA are normally expressed in rat ileum at 17 days of postnatal life. 14 kDa I-BABP is expressed considerably later in rat ovary. Corticosteroid treatment results in precocious expression of ileal 14 kDa I-BABP.

Age Factors↗
PubMed1996

Identification of genes whose expression is altered during mitosuppression in livers of ethinyl estradiol-treated female rats.

In this study, our goal was to identify genes whose expression in liver is altered in female F-344 rats during mitosuppression induced by 42 days of ethinyl estradiol (EE) treatment (Yager et al., Carcinogenesis, 15, 2117-2123, 1994). Northern analysis demonstrated that the mRNA levels for transforming growth factor-beta1 (TGF-beta1) and the mannose 6-phosphate/insulin-like growth factor II receptor were significantly increased by EE treatment. Ten cDNA clones representing mRNAs whose expression was increased two- to four-fold in the mitosuppressed livers were identified by differential display. Sequence analysis revealed that one was homologous to the S-24 ribosomal protein and another to mitochondrial ATPase subunit e. The remaining clones showed no homology to known genes in GenBank. However, the expression of clones 15, 16 and 17 was increased in HepG2 cells following treatment with doxorubicin suggesting their induction by oxidative DNA damage. These results suggest that two independent but interrelated signalling pathways, one mediated through transforming growth factor-beta and the other through oxidative DNA damage, may contribute to hepatic mitosuppression caused by EE, perhaps through activation of cyclin-dependent kinase inhibitors.

Animals↗
PubMed1995

The role of mast cells in the development of skin fibrosis in tight-skin mutant mice.

Chronic inflammatory conditions can evolve a fibrotic phenotype often associated with an increase in the number of mast cells (MC) near or within the granulation tissue. Despite the potential of MC to mediate fibrosis, it is unclear whether these cells play a central role in the pathogenesis of fibrosis or whether their presence is simply circumstantial. The tight-skin (Tsk) mouse develops an inherited fibrotic disease (sharing many similarities with the human disease scleroderma, systemic sclerosis) in which the lesions are associated with increased numbers and heightened granule release implicating MC in the pathogenesis of fibrosis. Despite their close association with the skin fibrosis of Tsk mice, the precise role of the MC in the pathogenesis of this inherited disease is unknown. Therefore, to assess directly whether MC are key elements in the pathogenesis of Tsk fibrosis, we generated MC deficient mice carrying the Tsk locus by utilizing selective interbreeding between Tsk and mutant mice deficient in mast cells (W, dominant white-spotting). We found that in the absence of MC, the early natural history of Tsk fibrosis was not altered. Furthermore, in older (5-7 months) Tsk mice, we found that the number of cutaneous MC was correlated with a more pronounced fibrosis. Therefore, we conclude that Tsk skin lesions are a pleiotropic manifestation of the Tsk gene in which MC are involved/recruited by an uncharacterized mechanism and that subsequent proliferation and activation of MC leads to augmentation of fibrosis.

Animals↗
PubMed1995

Transforming growth factor-beta 1 and collagen gene expression during postnatal skin development and fibrosis in the tight-skin mouse.

BACKGROUND: The tight-skin (Tsk) mutation in the mouse leads to widespread connective tissue abnormalities characterized by excessive collagen deposition that is similar to that observed in human scleroderma. Heterozygous mice develop skin fibrosis shortly after birth, providing a valuable model to investigate the sequence of events leading to fibrosis. EXPERIMENTAL DESIGN: We have studied by in situ RNA hybridization the expression of procollagen alpha 1(I), alpha 1(III), alpha 2(VI) and transforming growth factor-beta 1 (TGF-beta 1) genes in the skin of Tsk mutant and normal newborn to aged mice. Tsk and normal skin sections at each age were mounted on the same slide to ensure identical experimental conditions, allowing for comparative analyses. RESULTS: All genes are under temporospatial regulation and exhibit characteristic patterns of expression during postnatal skin growth and development. TGF-beta 1 mRNA is detected in fibroblasts only during the rapid postnatal growth of the skin in parallel with high collagen I, III, and VI gene expression. Collagen I and III gene-expressing fibroblasts are observed in excess in the Tsk fibrotic lesions. An abnormal pattern of collagen VI expression is only observed at later stages in the fibrotic process. Collagen VI shows a different expression pattern in both normal skin development and fibrosis, suggesting noncoordinate regulation with collagen I and III genes. CONCLUSIONS: The fibrotic process in Tsk mice results from the persistence of high collagen I and III expression by a subpopulation of fibroblasts. Collagen VI overexpression participates later in the fibrotic process. In contrast with human scleroderma and other skin fibrotic diseases, TGF-beta 1 mRNA is not detected in the areas of abnormal collagen expression and fibrosis of Tsk. Alternative pathways should be explored to understand the abnormal extracellular matrix deposition of Tsk fibroblasts.

Animals↗
PubMed1995

Cervical myelopathy caused by pseudogout.

A case of pseudogout manifesting as a cervical myelopathy is presented. Surgery can offer the definitive treatment with removal of the compressing crystalline mass. This diagnosis should be considered in a progressive myelopathy in the elderly person shown to have extradural compression, even in the absence of other stigmata of gout.

Aged↗
PubMed1994

Molecular cloning, tissue distribution, and expression of a 14-kDa bile acid-binding protein from rat ileal cytosol.

A cDNA clone encoding the major intestinal cytosolic 14-kDa bile acid-binding protein (14-kDa I-BABP) was isolated from a rat ileal lambda gt22A library following immunoscreening using a monospecific antiserum raised against a 14-kDa polypeptide found in the rat ileal cytosol. One clone of 516 bp encoded a 128-amino acid protein with a predicted molecular mass of 14,544 Da. The deduced amino acid sequence of 14-kDa I-BABP showed 100% homology to rat intestinal 15-kDa protein (I-15P) and 72% homology to porcine 15-kDa gastrotropin, whereas comparison of I-BABP to rat 14-kDa fatty acid-binding proteins of liver, intestine, and heart revealed homologies of 44%, 25%, and 28%, respectively. Northern blot analysis revealed a single transcript of approximately 0.5 kb in ileum and ovary; however, the abundance of I-BABP mRNA was much greater in ileum than in ovary. No transcript was seen in RNA extracted from stomach, jejunum, colon, liver, adrenal, brain, heart, kidney, or testis. Transfection of the I-BABP cDNA into COS-7 cells resulted in the expression of a 14-kDa protein that was identical to the ileal cytosolic I-BABP as determined by immunoblotting. Photoaffinity labeling of expressed 14-kDa protein was saturable with respect to increasing concentrations of 7,7-azo[3H]taurocholate (Km, 83.3 microM; Vmax, 6.7 pmol/mg per 5 min). Taurocholate inhibited 7,7-azotaurocholate labeling by > 96% with lesser inhibition by taurochenodeoxycholate (83.1%), chenodeoxycholate (74.6%), cholate (50.5%), and progesterone (38.5%), whereas oleic acid and estradiol did not inhibit binding.

Amino Acid Sequence↗