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A Mitchell

Publications and source records attributed to A Mitchell.

At least 91 records · Page 5Linked to original sources
PubMed1998

Expression of prostaglandin G/H synthase type 1, but not type 2, in human ovarian adenocarcinomas.

Prostaglandin endoperoxide synthase (PGHS) is a key rate-limiting enzyme in prostaglandin biosynthesis. PGHS has recently been shown to be expressed in human colorectal cancers and in experimental cutaneous papillomas and carcinomas. However, PGHS expression has not been investigated in ovarian cancers. The objectives of this study were to determine whether PGHS isoenzymes are expressed in human ovarian cancer and, if so, to identify which isoform is involved (PGHS-1 and/or PGHS-2) and to characterize its cellular localization. Sixteen human ovarian adenocarcinomas were studied by immunohistochemistry using specific antibodies recognizing PGHS-1 or PGHS-2. Results showed that all adenocarcinomas demonstrated the presence of tumor cells expressing PGHS-1 but not PGHS-2. Patterns of staining of tumor cells varied among different types of adenocarcinomas, with cells presenting either a mostly diffuse cytoplasmic immunoreactivity or, alternatively, a staining mainly concentrated around the nucleus. No correlation between the intensity of the immunostaining and the degree of malignancy of tumors could be established (r 5 20.03; p>0.05). Immunoblot analysis with PGHS-1-selective antibodies of cell extracts from adenocarcinomas revealed the presence of a characteristic 72,000 Mr immunoreactive band. Therefore, these results show for the first time that PGHS-1 is expressed in human ovarian adenocarcinomas. (J Histochem Cytochem 46:77-84, 1998)

Adenocarcinoma, Mucinous↗
PubMed1998

New concepts regarding the pathogenesis of periodontal disease in HIV infection.

Periodontal manifestations of human immunodeficiency virus (HIV) infection were first described in 1987. Initially, the lesions receiving attention were HIV-associated gingivitis (now known as linear gingival erythema [LGE]) and HIV-associated periodontitis (now known as necrotizing ulcerative periodontitis [NUP]). The true prevalence of LGE was difficult to determine due to variable diagnostic criteria. Recently, LGE has been associated with intraoral Candida infection. The prevalence of NUP is low (< or = 5%), and this lesion is associated with pronounced immunosuppression. Current focus on the periodontal manifestations of HIV infection centers on rapid progression of chronic adult periodontitis in HIV+ patients. Attempts to identify the pathogenesis of the increased progression of periodontitis have not proven successful. For example, analysis of subgingival plaque for the presence of bacterial pathogens has failed to detect differences between HIV+ and HIV- patients. Recently our laboratory has identified alterations in the host response in the gingival crevice of HIV+ patients. Comparing HIV+ and HIV- injecting drug users (IDU), levels of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) in gingival crevicular fluid (GCF) were slightly elevated at sites with a probing depth of 1 to 3 mm. At deeper sites (> or = 4 mm), total IL-1 beta in GCF was significantly greater in HIV+ individuals. Using the lysosomal acid glycohydrolase beta-glucuronidase (beta G) as a measure of the influx of polymorphonuclear leukocytes (PMN) into the gingival crevice, our data indicated a significant correlation of total beta G in GCF and probing depth in the HIV-IDU (r = 76; P = .02). This result was similar to what we have observed in other studies. In contrast, for HIV+ subjects, total beta G was not associated with probing depth (r = .20; NS). These data suggest that HIV+ patients have altered regulation of PMN recruitment into the gingival crevice. We have begun to investigate the conditions under which subgingival Candida may contribute total periodontal lesions in HIV+ individuals. Candida from subgingival sites has been cultured in HIV+ individuals. Subgingival Candida was distinct from Candida isolated from tongue and buccal mucosal surfaces (as indicated by genomic fingerprinting). We hypothesize the absence of adequate priming of PMN by HIV+ patients. This may be due to a reduced Th1 lymphocyte response. The inability of HIV+ individuals to adequately prime PMN may allow Candida to colonize the subgingival environment. In that milieu, it may act directly or in concert with subgingival bacterial pathogens, or as a cofactor (by inducing production of proinflammatory cytokines) to increase the occurrence of periodontal attachment loss.

Candidiasis, Oral↗
PubMed1998

A candidate high density lipoprotein (HDL) receptor, HB2, with possible multiple functions shows sequence homology with adhesion molecules.

High density lipoprotein (HDL), an antiatherogenic lipoprotein comprises several subclasses differing in composition and metabolic function. This physiological complexity appears to be matched with the growing number of candidate HDL receptors, since several HDL binding proteins have recently been identified in various tissues. Because these putative receptors may signal different pathways it is important to identify their structure and potential role in HDL metabolism. We review recent progress in the cloning and characterization of HB2, one of a pair of HDL binding proteins (HB1 and HB2) first purified from rat liver. The structure of HB2 is consistent with a receptor role for this membrane protein and when expressed in cells, increases HDL binding 2 fold. HB2, minimally present in THP-1 cells, is substantially upregulated in macrophages and appears sensitive to cholesterol loading of these cells. The protein shows high homology with adhesion molecules ALCAM and BEN and the possibility that HDL by binding to HB2, reduces adhesion induced arterial wall injury, is discussed in the context of the known protective role of HDL against atherosclerosis. The possible functions of HB2 are also compared with other recently cloned HDL receptors.

Animals↗
PubMed1997

Influence of acute rejection episodes, HLA matching, and donor/recipient phenotype on the development of 'early' transplant-associated coronary artery disease.

BACKGROUND: Transplant-associated coronary artery disease (TxCAD) is the manifestation of chronic rejection in the cardiac allograft. Both immunological and nonimmunological factors contribute to its development. Stratification by the time of development of TxCAD has not been considered previously for an extensive transplant series and may provide a means for apportioning relative risk factors appropriately. Specifically, TxCAD that develops early may have a pathogenesis different from TxCAD that develops later; ie, immunological factors play a more significant role in early development of TxCAD compared with later forms of the disease or in recipients where it has not been found. METHODS AND RESULTS: Between 1980 and 1994, 550 heart transplant recipients with postmortem data or yearly angiograms, donor:recipient serological HLA typing, and biopsy data were reviewed. Recipients were divided into four groups: Very Early (<1 year), Early (1-2 years), Late (3-14 years), and None (clear angio >3 years). There was a significant association between the number of histologically proven acute rejection episodes within 3 months and at 1 year and the development of early TxCAD. The number of acute rejection episodes within 3 months and 1 year is also significantly related to freedom of development of TxCAD. There was no significant association between the mean number of mismatches for Class I or Class II antigens, nor could any Class I/II phenotype for recipient or donor be identified that exerted a protective or deleterious effect. A lack of any association or trend with HLA data is demonstrated. CONCLUSIONS: These differences in pathogenesis between early and late TxCAD help define the importance of acute rejection in the etiology of chronic cardiac rejection. Stratification by time of development of TxCAD may provide further insight into defining the relative importance of other risk factors associated with the development of TxCAD. The lack of association with HLA data is discussed.

Acute Disease↗
PubMed1997

Cloning and characterization of HB2, a candidate high density lipoprotein receptor. Sequence homology with members of the immunoglobulin superfamily of membrane proteins.

The protection against coronary artery disease attributed to high density lipoprotein (HDL) may be associated with several functions, including its central role in reverse cholesterol transport, possible antioxidant and antithrombotic properties and others not yet identified which may depend on specific interactions between HDL and cell receptors. Several HDL-binding proteins have been identified including two candidate liver HDL receptors, HB1 and HB2 recently purified in this laboratory. We now report the cloning, sequencing, and some properties of HB2, the most abundant of the pair. It shows significant homology with the adhesion molecules ALCAM and BEN of the immunoglobulin superfamily and the cDNA, when transfected into HepG2 or COS cells, caused specific HDL3 binding to increase by 80-100%. Further, ligand blotting of glycoproteins isolated from phorbol 12-myristate 13-acetate-treated THP-1 cells or from transfected HepG2 and Chinese hamster ovary cells also provided evidence of increased binding of HDL3 to HB2. Differentiation of THP-1 cells into macrophages resulted in a striking increase in HB2 mRNA which was attenuated if cells were cholesterol-loaded by incubation with acetylated low density lipoprotein. If the interaction between HDL and HB2 reduces the adhesion-induced inflammatory cellular events that characterize arterial wall injury, thereby achieving the protection associated with higher plasma levels of HDL, these findings may provide a clue to one mitigating effect of HDL in heart disease.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed1997

Determinants of transplant-related coronary calcium detected by ultrafast computed tomography scanning.

Coronary calcium detected by ultrafast computed tomography (CT) has been shown to be a marker of coronary artery disease in heart transplant recipients. The objective of this study was to examine the possible determinants of coronary calcium after heart transplantation. Over a 15-month period, 102 consecutive cardiac transplant recipients (mean age 53 years, 88 men) underwent ultrafast CT scanning of the heart, in addition to coronary angiography, to determine coronary calcium score on their annual follow-up (a median of 4.6 years [range 63 days to 9.1 years] after transplant). The following data were also recorded: the recipient's sex and date of birth, date of transplantation, date of ultrafast computed tomography and coronary angiography; recipient pretransplant diagnosis, history of diabetes mellitus and systemic hypertension, fasting lipid profile, immunosuppression, number of rejection episodes, and donor organ ischemic time. Forty six patients (45.1%) had total calcium scores >0 and 41 (40.2%) had at least 1 major coronary with angiographic narrowing >24%. On univariate analysis, coronary calcium was significantly associated with dyslipoproteinemia, total cholesterol was >6.0 mmol/L (240 mg/dl), triglycerides were >3.0 mmol/L (265 mg/dl), and lipoprotein(a) >30 mg/ dl; > or =25% angiographic disease was significantly associated with coronary calcium and dyslipoproteinemia. Logistic regression revealed that dyslipoproteinemia, systemic hypertension, and donor ischemic time were significant predictors of coronary calcium in transplanted hearts. We conclude that the prevalence of coronary calcium in heart transplant recipients is high and is related to recipient dyslipoproteinemia, systemic hypertension, and donor organ ischemic time.

Calcinosis↗
PubMed1997

Neoplastic transformation of the endocervix associated with downregulation of lactoferrin expression.

The incidence of cervical adenocarcinomas in young women over the last two decades has increased. Even with increasing knowledge of the role of human papillomavirus in the etiology of adenocarcinoma of the cervix, there is a paucity of data concerning the genetic and epigenetic factors that contribute to the histologic features and biologic behaviors of these tumors. Lactoferrin is a basic glycoprotein found in human milk, secondary granules of neutrophils, and many body secretions, and it has been associated with carcinogenesis of the endometrium, breast, and lymphoid systems. In this study, we examined the expression of lactoferrin in normal human endocervical epithelium and in cervical adenocarcinomas in relation to proliferative index, steroid receptor status, p53 protein expression, and apoptosis. Immunohistochemical and in situ studies demonstrated that lactoferrin protein and mRNA were strikingly downregulated upon neoplastic transformation of the endocervix as early as in adenocarcinoma in situ when compared with the prominent expression exhibited by the normal cervical epithelium. Furthermore, neoplastic transformation of endocervical epithelial cells was accompanied by a pronounced stimulation of proliferation and a substantial reduction in the expression of the estrogen and progesterone receptors and p53 but little or no change in the number of apoptotic cells. In conclusion, we identified lactoferrin as a novel cancer-specific marker of endocervical adenocarcinomas that may be useful in the early detection of the disease, prediction of prognosis, and the development of new therapeutic modalities.

Adenocarcinoma↗
PubMed1997

Acute colonic surgery and unrecognized hypothyroidism: a warning. Report of six cases.

PURPOSE: This study was designed to highlight the significant morbidity related to undetected hypothyroidism in the elderly who are undergoing emergency surgery. METHOD: Case reports of six patients who presented with acute colonic surgical conditions are reviewed. RESULTS: Six cases of undetected hypothyroidism in a group of elderly patients was unmasked at the time of surgery for acute colonic conditions or in the perioperative period. These patients experienced increased morbidity, but once detected and treated, all but one had an uneventful recovery. CONCLUSION: Unrecognized hypothyroidism may lead to unnecessary surgery or even a potentially fatal outcome. A heightened awareness of this not so uncommon entity is mandatory.

Aged↗
PubMed1997

Effects of chronic high-rate electrical stimulation on the cochlea and eighth nerve in the deafened guinea pig.

This study was undertaken to examine the effects of chronic high-rate stimulation on the eighth nerve and cochlea. Fifty-four male pigmented guinea pigs were deafened and implanted with single ball electrodes in scala tympani. Four groups of animals received chronic electrical stimulation at a level of 5 microCol/cm2/ph for 1000 h as follows: Group A: 1000 Hz, 100 microseconds/ph duration, 100 microA peak; Group B: 250 Hz, 100 microseconds/ph duration, 100 microA peak; Group C: 2750 Hz, 36 microseconds/ph duration, 250 microA peak; Group D: 250 Hz, 400 microseconds/ph duration, 25 microA peak. Also, two control groups received 20 min stimulation during weekly electrically evoked auditory brainstem response (eABR) measurement (Group E) and about 5 s stimulation (Group F) during a brief eABR 3 day postimplantation and at perfusion. On Day 50, animals were perfused, midmodiolar sections cut and a quantitative assessment of spiral ganglion cells (SGC) performed. All stimulated subjects showed a similar decrease in eABR thresholds and dynamic range over time. No stimulation conditions induced pathology. All stimulation conditions enhanced survival of SGCs compared to unimplanted ears and implanted non-stimulated ears (Group F). There were no statistically significant differences in SGC survival between any stimulated groups, including Group E stimulated once a week. In conclusion, high-rate stimulation, under the conditions of this study, provides no additional risks and the same benefits to SGC survival as low-rate stimulation.

Animals↗