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Biomedical subjects

M A Kahn

Publications and source records attributed to M A Kahn.

At least 37 records · Page 2Linked to original sources
PubMed1997

CNTF induces GFAP in a S-100 alpha brain cell population: the pattern of CNTF-alpha R suggests an indirect mode of action.

In a recent report, we demonstrated that intracerebral injections of the pleiotropic cytokine, ciliary neurotrophic factor (CNTF), into developing postnatal rats evoked a severe inflammatory response as determined by the appearance of reactive astrocytes and activated microglia. Considering the likely involvement of CNTF in the injury response, we felt it was important to further understand the role of CNTF in the developing rat CNS. In this study, we examined the responsiveness of other cell populations to intracerebral injections of CNTF. We report that CNTF increases glial fibrillary acidic protein (GFAP), while having no appreciable effect on the levels of other intermediate filaments including vimentin and neurofilament. Moreover, CNTF did not affect the expression of the mature oligodendrocyte gene, myelin basic protein. These results suggest that CNTF is highly specific in its regulation of GFAP. In our previous study, we showed CNTF to increase GFAP in a cell population that already exists in the CNS parenchyma. To determine the origin of the CNTF-induced reactive astrocytes, therefore, we have utilized a technique of combined in situ hybridization and immunocytochemistry. To examine the possibility that CNTF acts on oligodendrocyte precursors to give rise to reactive astrocytes, the platelet-derived growth factor alpha receptor (PDGF-alpha R) was utilized as a riboprobe in conjunction with an antibody to GFAP. Examination of CNTF-induced GFAP+ astrocytes revealed no colocalization with PDGF-alpha R mRNA. In contrast, when we utilized an S100 alpha antibody recognizing a calcium binding protein in immature astrocytes, we found colocalization of S100 alpha and GFAP mRNA. These data suggest that CNTF induces an upregulation of GFAP in immature S100 alpha + astrocytes. Examination of the CNTF-alpha receptor mRNA revealed no change in expression following CNTF treatment. Unexpectedly, however, the CNTF-induced astrogliotic response appears to be indirect since the CNTF-alpha receptor was solely expressed by neurons in the cytokine-treated animals.

Animals↗
PubMed1997

Polymorphous low-grade adenocarcinoma: flow cytometric, p53, and PCNA analysis.

Polymorphous low-grade adenocarcinoma of minor salivary glands (terminal duct carcinoma, lobular carcinoma) was first defined more than a decade ago. A 17% recurrence rate and a 9% metastasis rate have been reported. Fifteen formalin-fixed, paraffin-embedded archival cases were analyzed. Ploidy and proliferative activity were evaluated with flow cytometric analysis. Demonstration of an abnormal p53 gene product and proliferative cell nuclear antigen analyses were also performed with routine immunohistochemical procedures. The purpose of this investigation was to evaluate these parameters and determine if a correlation existed. Flow cytometry was performed on 10 cases; 3 showed an aneuploid cell line (mean, S-phase diploid tumor cells 5.9%; S-phase aneuploid 26.7%). Products of a mutation of the p53 tumor suppressor gene have been noted to accumulate in salivary gland tumors, both benign and malignant. Qualitative assessment revealed p53 positive staining in 4 of 15 tumors; positive cells comprised 5% to 10% of the tumor. The percentage of tumor cells positive for proliferative cell nuclear antigen staining ranged from 0.5% to 70%. There was no correlation between proliferative activity as determined by proliferative cell nuclear antigen when compared with results of flow cytometric analysis except for one case that exhibited p53 staining, a 26% proliferative cell nuclear antigen fraction, and a distinct aneuploid cell line.

Adenocarcinoma↗
PubMed1997

Oral mucosal melanomas: the WESTOP Banff workshop proceedings. Western Society of Teachers of Oral Pathology.

A workshop to discuss primary oral melanomas was convened at the annual Western Society of Teachers of Oral Pathology meeting in Bannf, Alberta, Canada. Fifty oral melanomas, identified from the files of the participants, were reviewed in order to better understand the clinical features, histologic spectrum, and natural history of these perplexing lesions. Results confirmed that oral melanomas occur in adults almost three times more frequently in men than women and have a decided predilection for the palate and gingiva. Some lesions exhibit a clinically detectable and prolonged in situ growth phase, whereas others seem to lack this property and exhibit only or predominantly invasive characteristics. Recurrences, metastases, and death from tumor were characteristic of the follow-up of a limited number of patients. Until definitive prospective data are collected that elucidate natural history, oral mucosal melanomas should be tracked separately from cutaneous lesions. All oral pigmented lesions that are not clinically diagnostic should be biopsied. Lesions with equivocal histopathologic features might be referred to as "atypical melanocytic proliferation" and should be excised. Recognition of lesions in an early in situ phase and aggressive treatment should have a favorable effect on prognosis. To enhance future or prospective study of these rare neoplasms, guidelines for reporting oral melanomas are suggested.

Adult↗
PubMed1997

Ciliary neurotrophic factor activates JAK/Stat signal transduction cascade and induces transcriptional expression of glial fibrillary acidic protein in glial cells.

In recent reports, ciliary neurotrophic factor (CNTF) has been implicated as an injury factor involved in regulating astrogliosis in the CNS. In this study, we used a rat oligodendroglial progenitor cell line that is highly responsive to CNTF to examine CNTF-induced alterations that may play a role in activation of the glial fibrillary acidic protein (GFAP) gene. We determined that CNTF induces the transient translocation of Stat1 alpha/p91 to the nucleus. This nuclear translocation was followed by GFAP promoter activation and an up-regulation of GFAP mRNA and protein. Level of CNTF-alpha receptor mRNA, however, were unaffected by addition of the ligand. Transfection studies using an upstream 5'-flanking, 1.9-kb rat GFAP promoter linked to a luciferase reporter gene revealed CNTF-induced transcriptional activation within 1 h of ligand exposure. Moreover, serial-deleted constructs identified a distal (-1,857 to -1,546 bp) and a proximal (-384 to -106 bp) region as being important for CNTF-induced GFAP promoter activation. These two regions showed a strong degree of overlap for CNTF- and serum-induced activation of the GFAP gene. Analysis of the two regions revealed several cis-elements that are thought to be involved in GFAP regulation and/or the regulation of other genes by members of the interleukin-6 family of cytokines. Moreover, we are the first to report the presence of several putative CNTF-responsive elements within our identified distal and proximal regions in the GFAP gene promoter.

Acute-Phase Proteins↗
PubMed1997

Posterior colporrhaphy: its effects on bowel and sexual function.

OBJECTIVE: To determine the anatomical cure rate of posterior colporrhaphy and its effect on bowel and sexual function one to six years later. DESIGN: Retrospective observational study. SETTING: Urogynaecology Unit, St George's Hospital, London. PARTICIPANTS: Two hundred and thirty-one women who underwent posterior colporrhaphy. MAIN OUTCOME MEASURES: Anatomical and symptomatic cure of rectocoele. METHODS: The charts of 231 women who underwent 244 posterior colporrhaphies between 1 January 1989 and 4 January 1994 were reviewed. One hundred and seventy one (74%) were interviewed; 140 (61%) were examined. Mean follow up time was 42.5 months (range 11-74). RESULTS: Two hundred and nine women had prior or concurrent vaginal and/or bladder neck surgery including 38 previous posterior colporrhaphies. Postoperatively prolapse symptoms due to rectocoele decreased (64% vs 31%). Constipation (22% vs 33%), incomplete bowel emptying (27% vs 38%), incontinence of faeces (4% vs 11%) and sexual dysfunction (18% vs 27%) increased. Those with incontinence of stool were more likely to have had two or more posterior colporrhaphies. Sixty-two percent felt that they improved over all after surgery. Additional postoperative symptoms included: vaginal and/or perineal splinting (33%), soiling and/or inability to wipe clean (16%), rectal digitation (23%), incontinence of flatus (19%), and rectal and/or vaginal pain (22%). Thirty-three women (24%) had large rectocoeles, seven of whom did not have impaired bowel emptying. CONCLUSIONS: Posterior colporrhaphy corrects the vaginal defect in 76% of women. It does not necessarily correct and may contribute to bowel and sexual dysfunction, particularly in those requiring multiple procedures. The presence of the anatomical defect does not imply dysfunction. The prevalence of bowel symptoms suggests the need for close questioning about bowel habits and the selective use of bowel investigations for some women before surgery.

Adult↗
PubMed1996

RET protooncogene mutational analysis in multiple endocrine neoplasia syndrome type 2B: case report and review of the literature.

Multiple endocrine neoplasia, type 2B (MEN 2B), is a phenotypic variant of a group of autosomal-dominant neurocristopathies. MEN 2B is associated with medullary thyroid carcinoma and pheochromocytoma with oral, ocular, and alimentary submucosal ganglioneuromas and Marfanoid body features. Approximately 50% of cases are thought to be spontaneous mutations. The RET protooncogene (RET) is a 21-exon gene encoding a tyrosine kinase receptor. A codon 918 germ line mutation, which converts a highly conserved methionine to a threonine in the intracellular tyrosine kinase portion of this receptor of RET, has been identified in 95% of patients with MEN 2B. This mutation is easily detected by a direct deoxyribonucleic acid sequencing or restriction enzyme (Fok 1) analysis of amplified polymerase chain reaction products. The RET gene is normally expressed in the oral and gastrointestinal submucosal neural ganglia, and the codon 918 mutation is thought to cause neuromas by virtue of its transforming activity in these ganglia. Identifying clinical features of MEN 2B in an 11-year-old boy by an oral pathologist led to confirmation by mutational analysis. Before genetic testing was available, the patient, and at a later date his mother, underwent thyroidectomies based solely on biochemical testing. Results indicated the patient had the codon 918 mutation, whereas his phenotypically normal mother, father, and older brother had normal RET analyses. Studies in families have demonstrated that the mutant allele is derived from the father with possible acquisition during spermatogenesis. We believe the mother of our affected patient to be normal; the absence of phenotypic features of MEN 2B and a normal genotype suggest her calcitonin abnormalities and minimal evidence for C-cell hyperplasia were inconsequential. Molecular analysis for RET abnormalities will likely supplant biochemical methods of diagnosis in patients with MEN 2B.

Carcinoma, Medullary↗
PubMed1995

CNTF regulation of astrogliosis and the activation of microglia in the developing rat central nervous system.

In response to physical or chemical brain injury, the mammalian central nervous system (CNS) often reacts by evoking astrogliosis. The most prominent feature describing this state is an upregulation of glial fibrillary acidic protein (GFAP). The agent(s) responsible for inducing astrogliosis remains unclear; however, recent observations have shown cytokines may play a pivotal role. During CNS trauma, macrophages and lymphocytes infiltrate the CNS where they are thought to synthesize and secrete cytokines; moreover, activated microglia and reactive astrocytes are known to be capable of cytokine production. We are the first to report that an intracerebral injection of the pleiotropic cytokine, ciliary neurotrophic factor (CNTF), increases astrogliosis and the appearance of activated microglia in the neonatal rat. This response to CNTF was comparable to the response observed in animals receiving a well known pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha). Only a moderate increase was observed in the proliferative index of cytokine-injected animals; therefore, we conclude that GFAP is largely upregulated in a pre-existing GFAP negative cell population. Interestingly, coinjections of CNTF and TNF-alpha appeared to act synergistically. Coinjected animals displayed a wave of hypertrophied astrocytes reaching far into the contralateral hemisphere. No contralateral spreading of microglia was observed. This article clearly provides interesting information regarding the regulatory mechanisms that govern astrogliosis and discusses the probable relationship of reactive astrocytes to microglia.

Animals↗
PubMed1994

Regulation of an oligodendrocyte progenitor cell line by the interleukin-6 family of cytokines.

We report pleiotropic actions of the interleukin-6 family of cytokines on a rat cerebral cortical oligodendrocyte cell line, Central Glia-4 (CG-4). This is a bipotential oligodendrocyte type-2 astrocyte (O-2A) progenitor cell line that can be manipulated in vitro to become either a type-2 astrocyte or to follow a linear sequence of events into becoming a mature oligodendrocyte. Using Northern and Western analyses in conjunction with immunocytochemistry we have demonstrated that ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and interleukin-6 (IL-6) cause a transient increase in glial fibrillary acidic protein (GFAP) in oligodendrocyte type-2 astrocyte (O-2A) progenitor cells. At maximal cytokine concentrations, the largest increase in GFAP protein levels were observed for CNTF and LIF; albeit, IL-6 did increase GFAP but the order of magnitude was 6-7 times less. Moreover, in trophic factor deprived medium, CNTF and LIF protected immature (O4+/MBP-) and mature (MBP+) oligodendrocytes from the apoptotic mode of cell death, while IL-6 had no effect in enhancing oligodendrocyte cell survival. Analysis of the cytokine-induced early response genes (ERGs) revealed a strong degree of overlap for CNTF and LIF. The effect of IL-6 was different in the degree to which the ERGs were up-regulated and in their temporal patterns of expression. These findings suggest that ERGs may be important, at least in part, for determining the extent of functional overlap observed within this cytokine family. Our findings clearly demonstrate differential regulation of oligodendrocyte survival and differentiation by the IL-6 family of cytokines.

Apoptosis↗
PubMed1994

Proliferative verrucous leukoplakia. Four cases with flow cytometric analysis.

Proliferative verrucous leukoplakia is a slow-growing but highly aggressive precancerous form of leukoplakia of unknown cause. Proliferative verrucous leukoplakia is though to possess a continuous spectrum of clinical and histopathologic expression, ranging from simple hyperkeratosis to invasive squamous cell carcinoma. Early diagnosis is difficult because of an initial innocuous character, but multiple and rapid multifocal warty recurrences are common. This article reports four additional archival cases of proliferative verrucous leukoplakia to determine if flow cytometric analysis can be useful in the early diagnosis of proliferative verrucous leukoplakia. Flow cytometric analysis was performed on available formalin-fixed paraffin-embedded specimens (N = 27). Flow cytometric analysis results showed DNA aneuploid cell lines in each proliferative verrucous leukoplakia case studied (DNA index range, 1.1 to 2.6). In all four patients the abnormal cell line DNA index appeared to be maintained throughout the sampling period. The results suggest flow cytometric analysis could be a possible aid in early recognition of proliferative verrucous leukoplakia and might enable aggressive therapy at an earlier stage.

Aged↗
PubMed1993

Comparing flow cytometric analysis and nucleolar organizer region enumeration in archival oral premalignant lesions.

Flow cytometric analysis (FCA) and silver colloidal nucleolar organizer region-associated protein staining (AgNOR) have been used individually in assessing the histopathologic nature of various human tumors. However, few researchers have investigated the relationship between the two techniques in a single series. In a retrospective study, we examined 36 premalignant lesions of the oral cavity by FCA and AgNOR on formalin-fixed, paraffin-embedded tissue submitted to the University of Tennessee, Memphis, oral pathology laboratory. Three categories of epithelial dysplasia were represented (9 mild, 9 moderate, 6 severe), as well as four epithelial hyperplasias without dysplasia, three squamous cell carcinomas, and five fibrous nodules as controls. Parameters recorded for each case included age, race, gender, site, light microscopic diagnosis (LMD), DNA index (DI), total proliferative index (TPI), S-phase (S), range of nucleolar organizer regions (RNOR), and mean number of nucleolar organizer regions (MNOR). The average maximum nucleolar organizer region count (AMXNOR) for each LMD category was also calculated. The objective of the study was to determine if FCA or AgNOR aided in the subjective LMD of oral premalignant lesions and if the parameters recorded for the specimens exhibited any positive correlation. The FCA results indicated an abnormal DI in 6 of the 24 dysplastic lesions. A positive partial correlation was seen between DI and MNOR (r = 0.434; P < 0.012) and TPI and S (r = 0.774; P < 0.0001), holding gender and race constant. Additionally, the AMXNOR exhibited a slight tendency to increase for each increasing grade of dysplasia but this could not be confirmed statistically.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Demonstration of human papillomavirus DNA in a peripheral ameloblastoma by in situ hybridization.

The peripheral ameloblastoma (PA) is a rare, extraosseous, odontogenic lesion usually located on the mandibular or maxillary gingiva. It often appears as an asymptomatic, firm, pink-red nodule with occasional secondary involvement of the underlying bone. Although histologically identical to primary intraosseous ameloblastoma, the PA is notably less aggressive in biologic behavior and rarely recurs following conservative treatment. It has a proposed dual histogenesis, while its etiology remains obscure. Several benign oral mucosal lesions have been found to be associated with various types of human papillomavirus (HPV). The following study uses a commercially available HPV DNA in situ hybridization technique to confirm the presence of HPV in a previously reported case of PA. Results were positive for HPV types 16/18 but negative for HPV types 6/11. The implications of these results with regard to etiology are discussed.

Adolescent↗
PubMed1992

Mucinous ovarian tumors with pseudomyxoma peritonei: a clinicopathological study.

Eight patients with mucinous ovarian tumors and pseudomyxoma peritonei were matched by their original ovarian tumor histology with eight tumor controls without pseudomyxoma peritonei. In each group, four tumors were benign, three were low malignant potential, and one was malignant. Cases compared with controls more frequently showed cyst rupture (3 vs. 2), periovarian adhesions (5 vs. 4), mucinous lesions of the appendix (4 vs. 0), goblet cells (8 vs. 4), and tumor necrosis (3 vs. 1). All cases displayed pseudomyxoma ovarii, which contained mucinous epithelial cells. Only one control exhibited pseudomyxoma ovarii, but it did not contain epithelial cells. In all cases, the peritoneal mucin contained epithelial cells. Two cases were noteworthy, each of which displayed a change in histology (benign to low malignant potential and benign to malignant) 6 years after the original ovarian tumor operation. One of these cases was not associated with pseudomyxoma peritonei until the first recurrence of the benign ovarian tumor. These data suggest that pseudomyxoma ovarii, with epithelial cells, may presage the development of pseudomyxoma peritonei and/or malignant recurrence.

Appendiceal Neoplasms↗