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Biomedical subjects

A Katz

Publications and source records attributed to A Katz.

At least 127 records · Page 7Linked to original sources
PubMed1998

Contrasting internalization kinetics of human and chicken gonadotropin-releasing hormone receptors mediated by C-terminal tail.

The chicken gonadotropin-releasing hormone receptor (GnRH-R) is notable for having a cytoplasmic C-terminal tail, which is not present in the mammalian GnRH-Rs. We report here that the cytoplasmic tail mediates rapid agonist-promoted receptor internalization. The chicken GnRH-R mediated internalization of gonadotropin-releasing hormone (GnRH) agonist (125I[His5-D-Tyr6]GnRH) at a rate of 11.3%.min-1, compared with only 0.71 %.min-1 for the human GnRH-R. To determine whether the presence of the cytoplasmic tail was responsible for the more rapid internalization kinetics of the chicken GnRH-R we truncated the tail after the Ile336 residue (S337stop). Receptor-mediated internalization of GnRH agonist by the S337stop-chicken GnRH-R was much slower than in the wild-type chicken receptor, and was similar to the wild-type human GnRH-R (0.55 %.min-1). These data indicate that rapid agonist-promoted internalization of the chicken GnRH-R is mediated through elements in the cytoplasmic C-terminal tail, distal to or including Ser337 and suggests that elimination of the C-terminal tail during evolution of mammalian GnRH-Rs may be related to its effects on internalization.

Animals↗
PubMed1998

Increased sensitivity of IL-6-deficient mice to carbon tetrachloride hepatotoxicity and protection with an IL-6 receptor-IL-6 chimera.

Interleukin-6 (IL-6)-deficient mice were found to be much more sensitive to liver injury by carbon tetrachloride (CCl4) than mice with an intact IL-6 system. At doses of CCl4 ranging from 2 to 3.5 ml/kg body weight, mean mortality in the IL-6 gene knockout (IL-6-/-) mice was 71% at 24 hours versus 12% in normal IL-6+/+ mice. At sublethal doses, there was extensive parenchymal necrosis in the livers of IL-6-deficient mice, which was not seen in the control animals. Lipid peroxidation induced by CCl4 was up to 10-fold higher in the IL-6-/- mice. Injections of a chimeric protein containing IL-6 fused to its soluble receptor (IL-6R-IL-6 chimera) induced hepatocyte protection against CCl4 damage in both IL-6-/- and IL-6+/+ mice. Treatment with IL-6R-IL-6 restored the survival of the IL-6-/- mice to the level of IL-6+/+ animals. Free IL-6 was not effective in reducing CCl4-induced liver toxicity, but was as effective as IL-6R-IL-6 in reducing death from metastases in a murine melanoma model. Hence the IL-6R-IL-6 chimera appears to be particularly effective against chemical hepatotoxic injury.

Aldehydes↗
PubMed1998

Screening for disease in pregnancy.

Screening during pregnancy is unlike screening any other population, because two entities are involved and potentially affected by the disease: the pregnant woman and the fetus. A number of serum screening tests can be performed as part of prenatal care. Some are routinely done on all pregnant women, some are offered to women thought to be at risk for a particular disease, and some are offered according to the woman's age, country of origin or other criterion.

Adult↗
PubMed1998

In vivo native cellular fluorescence and histological characteristics of head and neck cancer.

Native cellular fluorescence (NCF) represents the innate capacity of tissues to absorb and emit light of a specified wavelength. The ability to define the relationship of in vivo NCF with biological characteristics of neoplastic disease may allow for an improved understanding of the clinical course of disease. Head and neck cancers from 35 patients were evaluated in vivo for NCF characteristics using a xenon lamp-based spectrometer coupled to a handheld fiberoptic probe. Spectral assessment was limited to lambda 450-nm emission characteristics, in which tissues were excited at various wavelengths, ranging from lambda 290 nm to lambda 415 nm, and the intensity of lambda 450 nm emission was recorded. Each cancer was subsequently biopsied and assessed for histological differentiation by a pathologist who was blinded to NCF analysis. Considerable variation in spectral characteristics between head and neck cancers was identified, which was determined, in part, by NCF characteristics of the normal mucosa from the same patient. Poorly differentiated tumors were more likely than well- or moderately differentiated tumors to have lower excitation maxima (P < 0.05 by ANOVA). Most significantly, the tumor differentiation status, as well as the probability of demonstrating recurrent disease, could also be related to the NCF characteristics of the patient's normal mucosa from the same site within the upper aerodigestive tract. NCF analysis may represent an effective tool to identify biological characteristics of head and neck tumors in vivo without the need for invasive biopsies. Results suggest the need to explore the determinants of NCF characteristics expressed by clinically normal mucosa.

Adult↗
PubMed1998

Cervical cancer screening.

OBJECTIVE: To review the role of family physicians in screening for cancer of the cervix, to review the evidence for screening, in particular, frequency and technique for screening, and to review the reasons cervical cancer has not been prevented and the role of family physicians in addressing these failures. QUALITY OF EVIDENCE: The value of screening has been established with level II evidence. Many of the unresolved issues are not supported either way by good evidence; level II and III evidence predominates. MAIN FINDINGS: In Canada, 1350 women were predicted to be diagnosed with cancer of the cervix in 1996. Most of these women had not been screened. Minority, rural, low-income, and older women face important barriers to screening. Family physicians have a role in reaching out to these women to provide effective health care, including cancer screening. When cancer screening is performed, it should conform to recommended techniques with appropriate follow up of abnormal test results. CONCLUSIONS: Family physicians have an important role in preventing cancer of the cervix. Efforts should be concentrated on encouraging a greater proportion of eligible women to be screened. Criteria are suggested for effective screening.

Diagnostic Errors↗
PubMed1998

Root positioning and leakage to dye in extracted teeth using reduced pressure.

A study was conducted in vitro to assess the root apex position on leakage to dye under reduced pressure (560 mm Hg). A total of 132 extracted single-rooted teeth were randomly allocated to four groups. The teeth were prepared using a step-back technique and sealed with the cold lateral condensation technique, using gutta-percha without sealer. No significant differences (P < 0.813) were found between horizontally positioned experimental groups under reduced pressure and those in passive immersion. In the group in which the apices were in an upright position, the mean leakage was significantly different (P < 0.024) from the mean dye penetration in the group of teeth positioned horizontally under reduced pressure. Those teeth with apices upright allowed the most linear leakage (0.51 mm), whereas the groups in which the roots were horizontally positioned (with and without reduced pressure) had the least dye penetration (0.21 mm and 0.19 mm, respectively). These results show that tooth positioning has a significant effect on linear dye penetration under reduced pressure and emphasize the need to standardize factors that may influence penetration when assessing leakage study methodology.

Coloring Agents↗
PubMed1998

Comparison of apical leakage shown by four different dyes with two evaluating methods.

A study was conducted in vitro to assess and compare the extent of apical leakage of four dyes by two commonly-used evaluation methods. For the study, 120 single-rooted extracted teeth were prepared by the step-back technique and obturated by lateral condensation with gutta-percha and Roth 801 sealer. After randomly allocating the roots into six groups, they were immediately immersed in dye for 72 h, using vacuum for 30 min at 40 degrees C. Teeth were immersed in Eosin, Methylene Blue, Black India Ink and Procion Brilliant Blue and cross-sectioned in 0.7 mm thick slices. Those immersed in Black India Ink and Procion Brilliant Blue were also evaluated by the clearing process. Dye penetration was assessed using a stereomicroscope. A statistically significant greater dye penetration was measured in the cross-sectioned group compared to the clearing group using the same dyes (Black India Ink, P = 0.020, Procion Brilliant Blue, P = 0.040). In the cross-section groups, no statistical significant difference was observed in the amount of leakage comparing the four dyes. No statistically significant difference was found in the leakage pattern of Procion Brilliant Blue and Black India Ink using the clearing technique (P = 0.797). The evaluating method (cross-sections versus clearing) rather than the dye properties was the main difference between results. More research is needed to standardize dye leakage studies.

Carbon↗
PubMed1998

Native fluorescence spectroscopy of normal and malignant epithelial cells.

Native fluorescence spectroscopy of normal human oral and malignant epithelial cells was studied under uv excitation. Differences were observed in the excitation spectra between normal and malignant epithelial cells for 340 nm emission. The observed differences may be utilized for both discrimination and changes associated with the amino acid residues in the cellular proteins.

Carcinoma, Squamous Cell↗
PubMed1997

The role of radiation therapy and chemotherapy in the treatment of Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma is a rare and highly aggressive skin tumor. The purpose of this study was to determine the role of radiation therapy and chemotherapy in the treatment of patients with Merkel cell carcinoma. METHODS: A retrospective analysis of 27 patients treated at Rabin Medical Center in Israel is presented, focusing on the treatment details. Data for 40 patients (the authors' 27 patients and an additional 13 patients from the Israeli Cancer Registry), were analyzed for prognostic factors using univariate and multivariate analyses. RESULTS: Univariate analyses revealed regional lymph node involvement and the coexistence of a second primary tumor as unfavorable prognostic factors. On multivariate analysis, only lymph node involvement showed borderline statistical significance. Radiation therapy was highly effective when given as consolidation after surgery or chemotherapy. In 11 patients irradiated effectively, only 1 (9%) in-field recurrence occurred. Radiation therapy yielded responses in 15 of 15 measurable sites (5 complete responses and 10 partial responses). Chemotherapy produced responses in 18 of 26 patients (69%), mostly complete (41%). However, in the absence of radiation therapy, the responses were short lived. CONCLUSIONS: These data support the use of combined treatment with chemotherapy followed by radiation therapy for patients with advanced locoregional Merkel cell carcinoma. In patients with metastatic disease, chemotherapy as well as radiotherapy can provide effective palliation. Further large scale investigations are warranted to confirm this approach.

Adult↗
PubMed1997

G protein betagamma complex-mediated apoptosis by familial Alzheimer's disease mutant of APP.

In familial Alzheimer's disease (FAD), three missense mutations, V642I, V642F and V642G, that co-segregate with the disease phenotype have been discovered in the 695 amino acid form of the amyloid precursor protein APP. Expression of these mutants causes a COS cell NK1 clone to undergo pertussis toxin-sensitive apoptosis in an FAD trait-linked manner by activating the G protein Go, which consists of G alpha(o) and G betagamma subunits. We investigated which subunit was responsible for the induction of apoptosis by V642I APP in NK1 cells. In the same system, expression of mutationally activated G alpha(o) or G alpha(i) induced little apoptosis. Apoptosis by V642I APP was antagonized by the overexpression of the carboxy-terminal amino acids 495-689 of the beta-adrenergic receptor kinase-1, which blocks the specific functions of G betagamma. Co-transfection of G beta2gamma2 cDNAs, but not that of other G beta(x)gamma(z) (x = 1-3; z = 2, 3), induced DNA fragmentation in a manner sensitive to bcl-2. These data implicate G betagamma as a cell death mediator for the FAD-associated mutant of APP.

Alzheimer Disease↗
PubMed1997

Unmasking by soluble IL-6 receptor of IL-6 effect on metastatic melanoma: growth inhibition and differentiation of B16-F10.9 tumor cells.

Interleukin-6 (IL-6) inhibits the growth of melanocytes and of early stage melanoma cells, but not that of advanced melanoma cells. The in vitro IL-6 response can be restored in the highly metastatic melanoma B16-F10.9 by addition of recombinant soluble IL-6 receptor alpha-chain (sIL-6R). The F10.9 cells then undergo irreversible growth-arrest and show increased adherence with changes from epithelioid to spindleoid morphology. The sIL-6R is required for IL-6 to induce a sustained activation of the various Stat transcription factors which bind to specific IL-6 inducible enhancers. The sIL-6R and IL-6 combination causes an increase in the level of the anti-oncogenic transcription factor IRF-1 protein and DNA-binding, which remain elevated for 24 h. The promoter activity of the anti-oncogenic p21/Waf-1/Cip-1 gene is induced and accumulation of the p21 protein is observed. These results illustrate the potent agonist activity of sIL-6R on molecular pathways which could mediate the growth-arrest and differentiation of the metastatic melanoma cells. Previously observed antimetastatic effects of IL-6 therapy in mice bearing F10.9 tumors may be at least partly due to direct growth inhibition and differentiation elicited by sIL-6R present in biological fluids.

Animals↗
PubMed1997

Individual CD34+CD38lowCD19-CD10- progenitor cells from human cord blood generate B lymphocytes and granulocytes.

Identification of human hematopoietic stem cells and analysis of molecular mechanisms regulating their function require biological assays that permit differentiation in all hematopoietic lineages simultaneously. In this study, we established conditions that permit the joint expression of the B-lymphoid and myeloid potential from cord blood-derived CD34+CD38lowCD19-/CD10- primitive progenitors that lack B-specific markers and transcripts. When cocultured during 6 weeks with the murine stromal cells MS-5 in the absence of exogenous human cytokines, CD34+CD38low-CD19-CD10- cells generated a high number of CD19+ B cells. Virtually all of these cells expressed a CD34-CD10+- CD19+cIgM- phenotype of late pro-B cells and transcripts of Pax-5, lambda-like, and mu chain were detected. We further show that 7% of CD34+CD38lowCD19- cells from cord blood, when grown individually with MS-5 cells, generated both CD19+ and CD11b+ cells after 6 weeks. Efficient B-cell differentiation was also observed in vivo after transplantation of human cord blood-derived unfractionated mononuclear cells or CD34+CD19+CD10- cells into immune-deficient mice. In contrast to the in vitro situation, all stages of B-cell differentiation were observed in vivo, including pro-B, pre-B, and sIgM+ B cells. Interestingly, human progenitors with the ability to differentiate along both B-lymphoid and granulocytic pathways were also detected among human CD34+CD38low cells in the marrow of chimeric mice 6 to 7 weeks after transplantation. Both in vitro and in vivo systems will offer an invaluable tool to further identify the lymphoid and myeloid potentialities of primitive progenitor cells isolated from fetal as well as adult human hematopoietic tissues and characterize stromal-derived signals that regulate their function.

ADP-ribosyl Cyclase↗
PubMed1997

Innate cellular fluorescence reflects alterations in cellular proliferation.

BACKGROUND AND OBJECTIVE: The objective of this study was to examine the question of whether unique spectral patterns were associated with cell proliferation and could be identified by comparing the fluorescence pattern of slow to rapid growing cells. STUDY DESIGN/MATERIALS AND METHODS: Three in vitro model systems, (A431 cells inhibited by EGF, serum-starved 3T3 fibroblasts, and normal oral epithelial cells exposed to TGF beta), were analyzed using fluorescence spectroscopy. Growth status was monitored by cell number, 3H-thymidine incorporation, and flow cytometry. RESULTS: The excitation spectra (lambda ex 240-430 nm, lambda em 450 nm) effectively distinguished slow and rapid growing cells in all three systems. Statistical analysis of the ratios of the main broad peak (320-350 nm) to a point on the down-slope of the curve at 370 nm was statistically significant. Ratios in the emission scan (lambda ex 340 nm, lambda em 360-660 nm) could separate slow and rapid growing A431 and oral epithelial cells (P = 0.0001 and P = 0.023, respectively), but not slow and fast growing 3T3 cells (P = 0.56). CONCLUSION: Innate cellular fluorescence has the potential to discriminate proliferating and nonproliferating cell populations.

Animals↗
PubMed1997

Insulin mediators in man: effects of glucose ingestion and insulin resistance.

Insulin mediators (inositol phosphoglycans) have been shown to mimic insulin action in vitro and in intact mammals, but it is not known which mediator is involved in insulin action under physiological conditions, nor is it known whether insulin resistance alters the mediator profile under such conditions. We therefore investigated the effects of glucose ingestion on changes in the bioactivity of serum inositol phosphoglycan-like substances (IPG) in healthy men and insulin resistant (obese, non-insulin-dependent diabetic) men. Two classes of mediators were partially purified from serum before and after glucose ingestion. The first was eluted from an anion exchange resin with HCl pH 2.0, and bioactivity was determined by activation of pyruvate dehydrogenase in vitro. The second was eluted with HCl pH 1.3, and bioactivity was determined by inhibition of cyclic AMP-dependent protein kinase. In healthy men, the bioactivity of the pH 1.3 IPG was not altered by glucose ingestion, whereas bioactivity of the pH 2.0 IPG increased to approximately 120% of the pre-glucose ingestion value at 60-240 min post-glucose ingestion (p < 0.05 vs pre-glucose). There was no change in either IPG after glucose ingestion in the insulin-resistant group. These data suggest that the pH 2.0 IPG plays an important role in mediating insulin's effect on peripheral glucose utilization in man under physiological conditions. The data further show, for the first time, a defective change in the bioactivity of an insulin mediator isolated from insulin-resistant humans after hyperinsulinaemia, suggesting that inadequate generation/release of IPGs is associated with insulin resistance.

Animals↗
PubMed1997

Inhibition of glomerular mesangial cell proliferation and extracellular matrix deposition by halofuginone.

Mesangial cell proliferation, increased deposition of collagen, and expansion of the mesangial extracellular matrix (ECM) are key features in the development of mesangioproliferative diseases. Halofuginone, a low molecular weight anti-coccidial quinoazolinone derivative, inhibits collagen type alpha 1(I) gene expression and synthesis. We investigated the effect of halofuginone on both normal and SV40 transformed mesangial cell proliferation, collagen synthesis, and ECM deposition. Proliferation of both cell types was almost completely inhibited in the presence of 50 ng/ml halofuginone. The cells were arrested in the late G1 phase of the cell cycle and resumed their normal growth rate following removal of the compound from the culture medium. The antiproliferative effect of halofuginone was associated with inhibition of tyrosine phosphorylation of cellular proteins. Similar results were obtained whether the mesangial cells were seeded on regular tissue culture plastic or in close contact with a naturally produced ECM resembling their local environment in vivo. Halofuginone also inhibited synthesis and deposition of ECM by mesangial cells as indicated by a substantial reduction in 14C-glycine and Na2(35)SO4 incorporation into the ECM, and by the inhibition of collagen type I synthesis and gene expression. It is proposed that by inhibiting collagen type I synthesis and matrix deposition, halofuginone exerts a potent antiproliferative effect that may be applied to inhibit mesangial cell proliferation and matrix expansion in a variety of chronic progressive glomerular diseases.

Animals↗
PubMed1997

Neutrophil superoxide release and interleukin 8 in acute myocardial infarction: distinction between complicated and uncomplicated states.

Superoxide release in neutrophils and sera levels of interleukin 8 (IL-8) were determined in 15 patients with complicated acute myocardial infarction (MI) and 15 patients with uncomplicated MI. All patients showed increased superoxide release in unstimulated and stimulated neutrophils compared with healthy control subjects, indicating priming of these cells. Superoxide release of unstimulated or stimulated neutrophils was found to be significantly higher in patients with complicated MI than in patients with uncomplicated MI. Thrombolytic therapy did not affect the rates of superoxide release. The neutrophil chemoattractant/activator IL-8 was detected in the sera of all patients, with significantly higher levels in those with complicated MI. The highest levels of IL-8 were detected at admission to the Coronary Care Unit and significantly decreased thereafter, suggesting its contribution to neutrophil-mediated tissue injury. The high levels of IL-8 may be one of the major contributors to the priming of neutrophils in these patients.

Aged↗
PubMed1997

'Mom, I have something to tell you'--disclosing HIV infection.

This paper explores the experience of disclosing HIV infection to family members. Information was obtained from secondary analysis of interviews conducted with 10 HIV-positive men and women. Learning that one is HIV-positive is a traumatic event, and disclosing this to family members can be difficult. Findings from this study suggest that family members generally overcome their own feelings and provide the infected individual with love and support. However, the resultant stress on the family may precipitate a crisis as secrets are brought into the open. Implications for nursing practice are addressed.

Adaptation, Psychological↗