Biomedical subjects

E Mann

Publications and source records attributed to E Mann.

At least 19 recordsLinked to original sources

PubMed2003

[Glomerular diseases in renal biopsy. Correlation of clinical syndromes with histological types].

Renal biopsies studied by light and electron microscopy as well as by immunohistochemistry seem to be continually necessary for an adequate typing and therapy of glomerulonephritis (GN) and other glomerular diseases. Basing on 653 renal biopsies examined in Rostock from 1990 to 1999, the morphological classification in a total of 585 cases with glomerular diseases is presented in comparison to their clinical syndromes according to the WHO classification. A nephrotic syndrome was most frequent and clinically reported in 258 of the 585 biopsy cases with glomerular diseases (44%). It was seen in 77 of the 87 cases with minimal change nephropathy (55%), in 46 of the 74 cases with focal segmental glomerulosclerosis (62%), and in 19 of the 24 diffuse membranous GN cases (79%). The majority of the varying histological subtypes of diffuse GN was not combined with a specific clinical syndrome except of diffuse crescentic GN presenting with a rapidly progressive nephritic syndrome in 14 of 16 cases (88%). IgA nephropathy was the most often diagnosed entity of glomerular diseases found in 122 of the 502 cases with primary or secondary GN (24%). It is obvious that a given morphological GN type can but must not be combined with a specific clinical GN syndrome, so that the clinical importance of renal biopsy is stressed.

Anti-Glomerular Basement Membrane Disease↗

PubMed2000

Effects of SU101 in combination with cytotoxic agents on the growth of subcutaneous tumor xenografts.

SU101 (leflunomide, N-[4-(trifluoromethyl)-phenyl] 5-methylisoxazole-4-carboxamide), an inhibitor of platelet-derived growth factor receptor signaling, has shown promising clinical activity in Phase I and II studies. Currently, SU101 in combination with cytotoxic agents is in late-stage clinical development for the treatment of cancers. In previous reports, efficacy in vivo versus varied tumor xenografts was observed. As part of the preclinical development of SU101 as a cancer therapy, the combination of SU101 with cytotoxic agents was studied in athymic mice bearing small, established, s.c. human tumor cell xenografts of glioblastoma (SF763T cells), lung (Calu-6 cells), or head and neck (KB cells) origin. In the SF763T model, the combination of SU101 with carmustine resulted in a statistically significant growth inhibition of 74% compared with the vehicle control; this combination was more effective than either agent alone. In the Calu-6 model, the combination of SU101, cisplatin, and etoposide resulted in a growth inhibition of 75% that was statistically greater than that of the vehicle-treated control group and groups treated with one or two agents. In the KB model, the combination of SU101, 5-fluorouracil, and cisplatin resulted in a statistically significant growth inhibition of 69% compared with the vehicle control. Treatment with one or two agents did not significantly inhibit growth in this model. Importantly, in addition to enhanced efficacy resulting from combination therapies, the combination treatments tested were well tolerated, as evidenced by lack of mortality. These data suggest that SU101 in combination with cytotoxic agents may provide clinical benefit and warrant further clinical investigation.

Animals↗

PubMed1999

Biochemical activities of extracts from Hypericum perforatum L. 3rd Communication: modulation of peroxidase activity as a simple method for standardization.

Alcoholic extracts from the herb "St. John's wort" (Hypericum perforatum L.) are widely used to counteract depressive situations, where the question on the mainly active principle is still under discussion. Thus, standardization of the drug on the basis of dry matter has been chosen instead of the popular leading component, hypericin. Inhibition of myeloperoxidase-catalyzed dimerization of enkephalins by Hypericum extracts has recently been reported. This method is based on the separation and quantification of enkephalin dimers by HPLC. In order to simplify this assay myeloperoxidase could be substituted by the cheaper horseradish peroxidase and the enkephalins by the amino acid tyrosine without loss of significance. In this communication we represent a more rapid photometric method based on peroxidase-catalyzed indole acetic acid oxidation suitable for quick, simple and economic drug standardization.

Chromatography, High Pressure Liquid↗

PubMed1999

Biochemical activities of extracts from Hypericum perforatum L. 4th Communication: influence of different cultivation methods.

Extracts from the herb "St. John's wort" (Hypericum perforatum L.), know since ancient times as medical plant, besides other activities such as wound healing, antighout, antirheumatic and diuretic properties, is used in the treatment of mild to moderate depression. Increasing application continuously makes cultivation under controlled conditions of Hypericum perforatum L. more important. This report shows the results of three-years cultivation experiments with Hypericum perforatum L. The findings indicate that N-fertilizing yields more plant material but results in a drug with less quantity of secondary metabolites. Important components of the drug were quantified by HPLC and their activities were analyzed with the aid of biochemical test systems. Narrowleaved and broadleaved varieties of Hypericum perforatum L. show differences both in activity and quality. In this experiments the most active extract was a methanolic extract derived from non-fertilized, broadleaved plants.

Anthracenes↗

PubMed1999

Evaluation of accuracy and repeatability of identification of food-borne pathogens by automated bacterial identification systems.

The performances of five automated microbial identification systems, relative to that of a reference identification system, for their ability to accurately and repeatedly identify six common food-borne pathogens were assessed. The systems assessed were the MicroLog system (Biolog Inc., Hayward, Calif.), the Microbial Identification System (MIS; MIDI Inc., Newark, Del.), the VITEK system (bioMérieux Vitek, Hazelwood, Mo.), the MicroScan WalkAway 40 system (Dade-MicroScan International, West Sacramento, Calif.), and the Replianalyzer system (Oxoid Inc., Nepean, Ontario, Canada). The sensitivities and specificities of these systems for the identification of food-borne isolates of Bacillus cereus, Campylobacter jejuni, Listeria monocytogenes, Staphylococcus aureus, Salmonella spp., and verotoxigenic Escherichia coli were determined with 40 reference positive isolates and 40 reference negative isolates for each pathogen. The sensitivities of these systems for the identification of these pathogens ranged from 42.5 to 100%, and the specificities of these systems for the identification of these pathogens ranged from 32.5 to 100%. Some of the systems had difficulty correctly identifying the reference isolates when the results were compared to those from the reference identification tests. The sensitivity of MIS for the identification of S. aureus, B. cereus, E. coli, and C. jejuni, for example, ranged from 47.5 to 72. 5%. The sensitivity of the Microlog system for the identification of E. coli was 72.5%, and the sensitivity of the VITEK system for the identification of B. cereus was 42.5%. The specificities of four of the five systems for the identification of all of the species tested with the available databases were greater than or equal to 97.5%; the exception was MIS for the identification of C. jejuni, which displayed a specificity of 32.5% when it was tested with reference negative isolates including Campylobacter coli and other Campylobacter species. All systems had >80% sensitivities for the identification of Salmonella species and Listeria species at the genus level. The repeatability of these systems for the identification of test isolates ranged from 30 to 100%. Not all systems included all six pathogens in their databases; thus, some species could not be tested with all systems. The choice of automated microbial identification system for the identification of a food-borne pathogen would depend on the availability of identification libraries within the systems and the performance of the systems for the identification of the pathogen.

Bacillus cereus↗

PubMed1999

Using acupuncture and acupressure to treat postoperative emesis.

Interest in non-pharmacological strategies to manage health-care problems is increasing. Effective treatment for postoperative nausea and vomiting continues to be elusive, despite the introduction of new anti-emetic drugs. Acupuncture and acupressure might offer an effective, safe, simple and cheap therapy.

Acupressure↗

PubMed1997

alpha-Amylase and salivary albumin adsorption onto titanium, enamel and dentin: an in vivo study.

In vivo adsorption of salivary albumin and alpha-amylase onto titanium, enamel and dentin was analysed following their exposure to the oral cavity for 2h. Oral appliances in six adults served as a platform for carrying 4-mm discs of the three materials. Adherent proteins were eluted from the discs and the amounts of salivary albumin and alpha-amylase were measured by an enzyme-linked immunosorbent assay. While significant difference between the adsorption of albumin and alpha-amylase onto enamel as compared with dentin was observed, adsorption onto titanium was significantly lower. A sample of whole saliva was also collected from each participant. The mean total amounts of albumin and alpha-amylase in the participants' whole saliva were 0.03 and 0.54 mg ml-1, respectively. Titanium adsorbed significantly less (4.43%) of the total albumin than did enamel (14.30%) or dentin (18.80%). No significant difference was found in the relative amounts of alpha-amylase adsorbed by the three materials. This significantly selective adsorption of proteins may enable the attachment of specific bacteria and thus alter the composition of the dental plaque and its potential pathogenicity.

Adsorption↗

PubMed1997

Inhibition of platelet-derived growth factor-mediated signal transduction and tumor growth by N-[4-(trifluoromethyl)-phenyl]5-methylisoxazole-4-carboxamide.

Many reports have cited coexpression of platelet-derived growth factor (PDGF) and its receptors by tumor cells or cells supporting tumor growth, suggesting both autocrine and paracrine mechanisms for PDGF-mediated tumor growth. We found that a small organic molecule, N-[4-(trifluoromethyl)phenyl] 5-methylisoxazole-4-carboxamide (SU101, leflunomide), inhibited PDGF-mediated signaling events, including receptor tyrosine phosphorylation, DNA synthesis, cell cycle progression, and cell proliferation. SU101 inhibited PDGF-stimulated tyrosine phosphorylation of PDGF receptor (PDGFR) beta in C6 (rat glioma) and NIH3T3 cells engineered to overexpress human PDGFRbeta (3T3-PDGFRbeta). SU101 blocked both PDGF- and epidermal growth factor (EGF)-stimulated DNA synthesis. Previously, this compound was shown to inhibit pyrimidine biosynthesis by interfering with the enzymatic activity of dihydroorotate dehydrogenase. In the current study, EGF-stimulated DNA synthesis was restored by the addition of saturating quantities of uridine, whereas PDGF-induced DNA synthesis was not, suggesting that the compound demonstrated some selectivity for the PDGFR pathway that was independent of pyrimidine biosynthesis. Selectivity was further demonstrated by the ability of the compound to block the entry of PDGF-stimulated cells into the S phase of the cell cycle, without affecting cell cycle progression of EGF-stimulated cells. In cell growth assays, SU101 selectively inhibited the growth of PDGFRbeta-expressing cell lines more efficiently than it inhibited the growth of PDGFRbeta-negative cell lines. SU101 inhibited the s.c., i.p., and intracerebral growth of a panel of cell lines including cells from glioma, ovarian, and prostate origin. In contrast, SU101 failed to inhibit the in vitro or s.c. growth of A431 and KB tumor cells, both of which express EGF receptor but not PDGFRbeta. SU101 also inhibited the growth of D1B and L1210 (murine leukemia) cells in syngeneic immunocompetent mice, without causing adverse effects on the immune response of the animals. In an i.p. model of tumor growth in syngeneic immunocompetent mice, SU101 prevented tumor growth and induced long-term survivors in animals implanted with 7TD1 (murine B-cell hybridoma) tumor cells. Because PDGFRbeta was detected on most of the tumor cell lines in which in vivo growth was inhibited by SU101, these data suggest that SU101 is an effective inhibitor of PDGF-driven tumor growth in vivo.

3T3 Cells↗

PubMed1996

Gender differences regarding peer influence and attitude toward substance abuse.

Gender role socialization differentially influences attitudes toward substance abuse for boys and girls. Students (n = 968, 456 = males, M age = 16.20, SD = 1.20) were administered a questionnaire to assess their perceptions of attitudes toward substance abuse. Boys' approval was significantly different than the level of approval estimated for girls on teenagers drinking beer or wine coolers chi 2 (4,n = 931) = 418.58, p < .00001, drinking hard liquor chi 2 (4,n = 921) = 432.49, p < .00001, driving after drinking chi 2 (4,n = 924) = 492.32, p < .00001, smoking marijuana chi 2 (4,n = 921) = 609.62, p < .00001, smoking cigarettes chi 2 (4,n = 927) = 480.35, p < .00001, taking diet pills to lose weight chi 2 (4,n = 914) = 185.05, p < .00001, and taking diet pills to get high chi 2 (4,n = 921) = 428.43, p < .00001. Teens viewed getting drunk at a party as more acceptable than driving after drinking 2 (4,n = 921) = 264.10, p < .00001, but gave boys more approval than girls for driving after drinking. Possible implications of these findings are discussed.

Adolescent↗

PubMed1996

Gastrin-releasing peptide receptor signaling resulting in growth inhibition.

We demonstrate that gastrin-releasing peptide (GRP) can inhibit the proliferation of human immortal nontumorigenic (184-B5) mammary epithelial cells ectopically expressing the human GRP receptor. Growth of Balb 3T3 cells ectopically expressing relatively high levels of the GRP receptor was also inhibited by GRP; however, growth of transfectants expressing lower levels of the receptor was not inhibited. Compared with Balb 3T3 cells, mammary epithelial cells could be rendered sensitive to growth inhibition by GRP by the expression of fewer GRP receptors. GRP also stimulated DNA synthesis in quiescent, serum-starved Balb 3T3 transfectants. In clones that were sensitive to growth inhibition by GRP by virtue of their expression of relatively high levels of the GRP receptor, the dose-response curve of GRP-stimulated DNA synthesis was bell shaped. This is consistent with our conclusion that the growth-inhibiting activity of GRP required the activation of a relatively large pool of receptors in Balb 3T3 cells. Significantly, prostaglandin H synthase inhibitors, which block the production of prostaglandins from arachidonic acid, reduced GRP-inhibitory effects on DNA synthesis. We also compared a number of GRP-stimulated signaling pathways in Balb 3T3 clones that were sensitive or insensitive to growth inhibition by GRP, including cAMP formation, phospholipase C activation, calcium mobilization, and arachidonic acid formation. Taken together, these results demonstrate a novel GRP receptor-coupled signal pathway promoting growth inhibition in which prostaglandin H synthase plays a significant role.

3T3 Cells↗

PubMed1996

Teen perspectives on HIV and the relevance of Hawaii's health providers.

Based on focus group interviews with adolescents from an urban Honolulu community, the present article describes how these adolescents view HIV, HIV-prevention and the role of health care providers in addressing HIV-related needs. Although medical providers are known to be knowledgeable experts in a variety of health care areas, other research points to an underutilization of this potential. While knowledgeable about HIV, many of the youth in this study continue to engage in risky behavior. Few perceive they have others they can meaningfully talk to about their HIV and other health concerns. Even when probed for, almost none of these teens saw health care providers as pertinent to HIV or their health beyond the traditional illness/prescription role. Suggestions for ways to get more involved in the prevention of HIV and, more generally, positive health development in teens are discussed.

Adolescent↗

PubMed1995

Serial quantitation of HPV-16 in the smears of women with mild and moderate dyskaryosis.

The aim of this study was to examine the efficacy of semi-quantitative polymerase chain reaction (PCR) testing in cervical smears as an adjunct to cytological surveillance in a cohort of women with mild or moderate dyskaryosis. The study population comprised a group of 62 women who underwent twelve months of cytological and colposcopic surveillance as part of a larger randomised prospective study of women with mild and moderate dyskaryosis. Semi-quantitative PCR for HPV-16 DNA was carried out on the initial and twelve month study smears before a large loop excision of the transformation zone (LLETZ) was carried out. Smears from a control population which comprised 167 women without a history of abnormal cervical cytology who were attending family planning and general practitioner clinics for routine cervical smears were tested similarly. The presence of high or intermediate levels of HPV-16 DNA on both the initial and twelve month study smear was positively associated with the identification of cervical intraepithelial neoplasia (CIN) grades II or III in the LLETZ specimen (P = 0.01). While the combination of HPV-16 DNA testing with cytology on a repeat cervical smear improved the selection of women with underlying CIN II/III, there was still a false negative rate of 53%. Twenty-nine women had 'low risk' levels of HPV-16 DNA and mild dyskaryosis or less on both repeat smears indicating suitability for surveillance, but in fact 34% of them had CIN II/III. This study supports the finding reported previously of an association between high and intermediate levels of HPV-16 DNA and CIN II/III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Psychological response to cervical screening.

BACKGROUND: Few studies have examined the psychological costs of cervical screening, despite expressed concern over possible negative sequelae. METHODS: Seventy-five women with mild or moderately dyskaryotic smears, under cytological surveillance, 75 women referred for colposcopy after a first-ever abnormal smear showing severe dyskaryosis, and 75 controls with recent negative cytology were interviewed at home, and their psychological adjustment was assessed. RESULTS: Levels of distress were higher among women with an abnormal smear than among controls with a recent negative smear. Anxiety (Hospital Anxiety and Depression Scale range 0-21, "normal" range 0-7) was highest among those referred for colposcopy (mean 8.12, controls 5.88, P < 0.001); afterward, distress fell (mean 6.61, P < 0.001) but more problems of social adjustment were evident (surveillance vs controls, P < 0.01). High anxiety was associated with social maladjustment (colposcopy, P < 0.001; surveillance, P < 0.01) and negative feelings about the self (P < 0.05). Current anxiety was unrelated to knowledge about abnormal smears, but in the surveillance group was related to satisfaction with the explanation provided (P < 0.05). CONCLUSION: A positive cervical smear may by psychologically traumatic for a significant minority of women, irrespective of management strategy.

Adaptation, Psychological↗

PubMed1995

Perceptions of family values and roles among Japanese Americans: clinical considerations.

A follow-up study of intact families in Hawaii found that Japanese Americans' perceptions of family values and roles were more likely than those of European Americans to reflect a hierarchical family status with greater role differentiation and the male role as central. Additionally, Japanese Americans emphasized collective harmony, cooperation, interpersonal acceptance, and positive mutual social interactions. Clinical implications of the findings are discussed.

Adolescent↗

PubMed1995

Organizational response to adolescent HIV risk.

Using semi-structured interviews, the present study examined organizational responses to adolescent HIV risk in an urban Honolulu community. All 23 health, social service, and educational organizations studied have been impacted by HIV. However, the overall organizational response has been compartmentalized and limited. Recommendations concerning improved organizational responses are provided.

Adolescent↗

PubMed1994

Inhibition of glioma cell growth by a truncated platelet-derived growth factor-beta receptor.

Abnormal expression of platelet-derived growth factor (PDGF) receptors has been observed in malignant glioma and other tumors such as osteosarcomas and malignant melanomas. However, their role in the development and maintenance of the tumors is not understood. Signaling through the PDGF receptors is activated by ligand-induced dimerization. Thus, introduction of mutant receptors that are kinase deficient but still dimerization competent is one strategy to study the importance of PDGF receptors in glioma cell growth. A truncated PDGF-beta receptor was introduced into C6 rat glioma cells and the PDGF-mediated signaling and subsequent cell growth studied. In clones expressing the mutant receptor, PDGF-BB-induced tyrosine phosphorylation of the endogenous receptor was significantly reduced. In addition, these cells grew to lower density in culture and formed smaller colonies in soft agar than the C6 parental cells. Furthermore, the ability of cells expressing the truncated receptor to grow as xenografts in nude mice was significantly impaired. These results support the important role for the PDGF-beta receptor in C6 glioma cell growth. They also demonstrate the usefulness of dominant-negative mutants of the PDGF receptor for the evaluation of the role of the receptor in tumorigenesis.

Animals↗

PubMed1994

Ligand-like effects induced by anti-c-erbB-2 antibodies do not correlate with and are not required for growth inhibition of human carcinoma cells.

The c-erbB-2 gene encodes a M(r) 185,000 tyrosine kinase receptor (p185) with extensive homology to the epidermal growth factor receptor. We have conducted mechanistic studies with several anti-p185 monoclonal antibodies (TAb 250, -255, -257, -260, and -263) directed against the extracellular domain of p185 utilizing the SKBR-3, BT-474, and SKOV-3 cancer cell lines. Several of these antibodies exhibited ligand-mimicking properties: they induced tyrosine phosphorylation of p185; increased the catalytic activity of the receptor substrate phospholipase C-gamma 1; exhibited time- and pH-dependent internalization; induced receptor down-regulation; and increased the turnover of the p185 protein delta 3-fold. However, there was not a universal correlation between the antibody-mediated ligand-like effects and growth inhibition. TAb 250 inhibited BT-474 cells but did not alter p185 phosphotyrosine content or increase receptor turnover in these cells. TAb 260 increased p185 protein turnover but did not affect proliferation of the SKOV-3 cell line. Furthermore, blockade of TAb 250-induced receptor phosphorylation with the tyrosine kinase inhibitor tyrphostin 50864-2 did not abrogate TAb 250-mediated growth inhibition of SKBR-3 cells. These data suggest that ligand-like effects mediated by p185 antibodies are not critical for the growth inhibition of c-erbB-2-overexpressing carcinoma cells.

Adenocarcinoma↗

PubMed1994

Cervical carcinoma in the Grampian region (1980-1991): a population-based study of survival and cervical cytology history.

OBJECTIVES: To study survival in women treated for cervical carcinoma in Grampian region, to identify clinical and pathological prognostic factors, and to correlate survival with cytology history. DESIGN: A retrospective study of all cases of cervical carcinoma using a prospectively gathered database. Data validated by 1 in 10 randomised retrospective case note sampling. SETTING: Aberdeen Royal Infirmary. SUBJECTS: Three hundred and sixty-three women resident within Grampian diagnosed as having cervical carcinoma between 1980 and 1991, with five-year survival data on the 206 diagnosed by the end of 1986. MAIN OUTCOME MEASURE: Five-year survival rates. RESULTS: The mean annual incidence of cervical carcinoma in our population was 11.2 per 100,000 women, with an overall five-year survival of 67% in those under 40 years of age and 60% in those aged 40 years and over. On univariate analysis, survival was significantly adversely affected by tumour stage, grade and absence of previous smears. On multivariate analysis, the effect of previous smear history was lost, but stage and grade remained strong independent risk factors for survival. There was no significant difference in five-year survival by age or tumour type. CONCLUSIONS: The prognosis of cervical carcinoma in Grampian region was independently affected only by stage of disease and tumour grading and cervical smear history.

Adult↗