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Biomedical subjects

J Kaplan

Publications and source records attributed to J Kaplan.

At least 109 records · Page 6Linked to original sources
PubMed1998

Psychosocial stress causes endothelial injury in cynomolgus monkeys via beta1-adrenoceptor activation.

Current evidence links psychosocial factors to exacerbation of diet-induced atherosclerosis in monkeys via activation of the sympathetic nervous system. However, it is uncertain whether these factors can potentiate initial lesion formation, and do so even in the absence of dietary provocation, and whether any such effects can be prevented by beta-adrenergic blockade. As endothelial injury has been considered an initiating event in atherogenesis, we studied the effect of psychosocial stress on endothelial integrity in 48 adult male cynomolgus monkeys (Macaca fascicularis). All animals were housed in 12 social groups of four monkeys each for 11 weeks. The monkeys in half of the groups were exposed to a socially unstable ('stressed') condition for 72 h and received saline (n = 8), a lipophilic beta1-blocker (metoprolol, 0.30 mg/kg per h; n = 8), or hydrophillic beta1-blocker (atenolol, 0.15 mg/kg per h; n = 8). The remaining six social groups were assigned to the socially stable (non-stressed) condition; for 72 h these animals all remained in their social groups and were similarly treated with saline (n = 8), metoprolol (n = 8), or atenolol (n = 8). The frequency of IgG-positive (injured) endothelial cells was estimated on en face (Häutchen) preparations from the thoracic aorta and coronary arteries. Psychosocial stress caused a significant increase in the number of injured endothelial cells in the circumostial areas of the descending thoracic aorta in the placebo group (0.3 vs. 0.8%, P < 0.02), an effect that had not been demonstrated previously. Moreover, beta-blockade significantly (P < 0.01) inhibited the stress effect, with no differences between the two beta-blocking agents. The number of injured endothelial cells in the non-branched portions of the aorta and coronary arteries were low and indistinguishable among groups; irregularities in the size and location of branching points in the coronary arteries precluded analysis of these sites. This study demonstrated that psychosocial stress induces endothelial injury, and that this effect is mediated via beta1-adrenoceptor activation.

Adult↗
PubMed1998

Exclusion of the apoE gene in autosomal dominant retinitis pigmentosa.

Our purpose was to search for mutations in the apolipoprotein E (apoE) gene and to evaluate the role of apoE polymorphisms in the occurrence of autosomal dominant retinitis pigmentosa (ADRP). The ApoE gene coding sequence was analyzed in 51 unrelated patients affected with ADRP. A screening for mutations by SSCP and an analysis of the apoE polymorphisms were performed using PCR and restriction enzymatic digestion. No abnormal patterns of migration were observed by SSCP analysis. No significant statistical difference was seen between our ADRP population and the French general population for apoE allele frequency. From these results we report that the apoE gene does not seems to be involved in our ADRP population.

Apolipoproteins E↗
PubMed1998

Cell line characterization and authentication.

Research and development involving the use of cell lines require precise knowledge of the purity and species of origin of the cell lines used. This can only be assured by periodic monitoring of cultured cell lines for possible contamination by other cells and for characteristics that authenticate the cell line identity. In the absence of such monitoring, inter- and intraspecies cell line contaminations are likely to occur in the laboratories of unsuspecting investigators and can result in the generation of mistaken conclusions with an attendant loss of investigators' time, effort, and resources. This chapter provides a history and an overview of the methods that have been developed for cell line authentication, the type of information each of these different methods provides, and how synthesis of that information can be used to characterize a cell line and confirm its identity. An effective cell line monitoring strategy is described that involves testing for a combination of genetic markers, including cell membrane species antigens, isoenzymes, chromosomes, and DNA fingerprints, and use of databases for each marker system to compare the results obtained with a test cell culture with results from an extensive panel of previously tested cell lines.

Animals↗
PubMed1998

Iron and copper transport in yeast and its relevance to human disease.

Recent progress in the field of copper and iron metabolism has resulted from a convergence of human and yeast genetics. The mechanisms of iron and copper transport are remarkably conserved between yeast and humans. Studies of the yeast homologs of human disease genes involved in metal homeostasis have shed light on the pathophysiology of these disorders.

Biological Transport, Active↗
PubMed1998

Phase I study of paclitaxel (taxol) and granulocyte colony stimulating factor (G-CSF) in patients with unresectable malignancy.

A phase I trial of a 24-hour infusion of paclitaxel was conducted to identify the maximum tolerated dose of paclitaxel with granulocyte colony-stimulating factor (G-CSF) in patients with unresectable malignancy previously untreated with chemotherapy. Nineteen patients with metastatic melanoma or non-small cell lung cancer were treated with paclitaxel administered at 250, 300, 400 mg/m2 every 3 weeks. G-CSF, 5 microg/kg was given as a daily subcutaneous injection 24 hours after the completion of the infusion. Dose limiting myelosuppression and peripheral neuropathy was observed at 400 mg/m2 and 350 mg/m2. Paclitaxel can be safely administered as a 24-hour infusion at 300 mg/m2 with G-CSF. Further studies of paclitaxel and G-CSF are recommended to determine a dose-response relationship in sensitive tumors.

Adult↗
PubMed1998

IL-2-activated murine newborn liver NK cells enhance engraftment of hematopoietic stem cells in MHC-mismatched recipients.

To explore the modulatory effects of IL-2-activated NK cells on hematopoietic stem cell (HSC) engraftment further, we used fresh newborn liver cells (NLC) and IL-2-activated newborn liver cells (ANLC) as combined sources, respectively, of transplanted HSC and IL-2-activated NK cells free of contaminating CD3+ T cells. As previously found with adult IL-2-activated spleen cells, NLC cultured with IL-2 for 7 days exhibited lymphokine-activated killer (LAK) activity, veto activity, and natural suppressor activity, and enhanced both short-term and long-term stem cell engraftment by intact co-injected syngeneic and allogeneic NLC in totally MHC-mismatched lethally irradiated recipients. However, unlike adult IL-2-stimulated adult spleen cells, IL-2-activated NLC lacked CD3+ T cells and failed to induce lethal GVHD. FACS analysis and cell sorting experiments showed that the cells in ANLC which enhanced short-term HSC engraftment belonged to the relatively immature CD3-NK1.1-2B4+ NK cell subset. By contrast, cells belonging to the more mature CD3-NK1.1+2B4+ NK cell subset showed no HSC-enhancing effects. Identification and isolation in humans of similar NK cell enhancers of HSC could lead to a new approach to improving stem cell engraftment in MHC-mismatched recipients without increasing the risk of GVHD.

Animals↗
PubMed1998

Zinc may regulate serum leptin concentrations in humans.

OBJECTIVE: Leptin, the product of the ob gene, plays a key role in a feedback loop that maintains energy balance by signaling the state of energy stores to the brain and by influencing the regulation of appetite and energy metabolism. Zinc also plays an important role in appetite regulation. Thus, we evaluated the relationship between zinc status and the leptin system in humans. METHODS: We studied nine healthy men with marginal zinc deficiency, induced by dietary means, before and after zinc supplementation. RESULTS: Zinc restriction decreased leptin levels while zinc supplementation of zinc-depleted subjects increased circulating leptin levels. In addition, zinc supplementation increased IL-2 and TNF-alpha production that could be responsible for the observed increase in leptin concentrations. CONCLUSIONS: Zinc may influence serum leptin levels, possibly by increasing the production of IL-2 and TNF-alpha.

Adult↗
PubMed1998

Nutritional and zinc status of head and neck cancer patients: an interpretive review.

In this review, we provide evidence based on our studies, for zinc deficiency and cell mediated immune disorders, and the effects of protein and zinc status on clinical morbidities in patients with head and neck cancer. We investigated subjects with newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx. Patients with metastatic disease and with severe co-morbidity were excluded. Nutritional assessment included dietary history, body composition, and prognostic nutritional index (PNI) determination. Zinc status was determined by zinc assay in plasma, lymphocytes, and granulocytes. Pretreatment zinc status and nutritional status were correlated with clinical outcomes in 47 patients. Assessment of immune functions included production of TH1 and TH2 cytokines, T cell subpopulations and cutaneous delayed hypersensitivity reaction to common antigens. At baseline approximately 50% of our subjects were zinc-deficient based on cellular zinc criteria and had decreased production of TH1 cytokines but not TH2 cytokines, decreased NK cell lytic activity and decreased proportion of CD4+ CD45RA+ cells in the peripheral blood. The tumor size and overall stage of the disease correlated with baseline zinc status but not with PNI, alcohol intake, or smoking. Zinc deficiency was associated with increased unplanned hospitalizations. The disease-free interval was highest for the group which had both zinc sufficient and nutrition sufficient status. Zinc deficiency and cell mediated immune dysfunctions were frequently present in patients with head and neck cancer when seen initially. Zinc deficiency resulted in an imbalance of TH1 and TH2 functions. Zinc deficiency was associated with increased tumor size, overall stage of the cancer and increased unplanned hospitalizations. These observations have broad implications in the management of patients with head and neck cancer.

Carcinoma, Squamous Cell↗
PubMed1998

Mutations in Emery-Dreifuss muscular dystrophy and their effects on emerin protein expression.

Seventeen families with Emery-Dreifuss muscular dystrophy (EDMD) have been studied both by DNA sequencing and by emerin protein expression. Fourteen had mutations in the X-linked emerin gene, while three showed evidence of autosomal inheritance. Twelve of the 14 emerin mutations caused early termination of translation. An in-frame deletion of six amino acids from the C-terminal transmembrane helix caused almost complete absence of emerin from muscle with no localization to the nuclear membrane, although mRNA levels were normal. This shows that mutant emerin proteins are unstable if they are unable to integrate into a membrane. A 22 bp deletion in the promoter region was expected to result in reduced emerin production, but normal amounts of emerin of normal size were found in leucocytes and lymphoblastoid cell lines. This shows that DNA analysis is necessary to exclude emerin mutations in suspected X-linked EDMD. Emerin levels in female carriers often deviated from the expected 50% and this was due, in at least two families, to skewed emerin mRNA expression from the normal and mutated alleles. In one family with a novel deletion of the last three exons of the emerin gene, a carrier had a cardiomyopathy and very low emerin levels (<5% of normal) due to skewed X-inactivation. In the three autosomal cases of EDMD, emerin was normal on western blots of blood cells, which suggests that autosomal EDMD is not caused by indirect reduction of emerin levels.

Adolescent↗
PubMed1998

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy.

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal-specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.

Adolescent↗
PubMed1998

Centerfire frangible ammunition: wounding potential and other forensic concerns.

Recently developed frangible ammunition of copper particulate construction in .38 Special, 9 mm, and .223 calibers was evaluated for wounding performance by firing into pigs' heads. The ability to match fired bullets with the corresponding gun was also examined. Results showed that wounds caused by 9-mm and .38 Special frangible bullets were comparable in severity to those caused by regular service ammunition of the same caliber. The recovered 9-mm and .38 Special bullets demonstrated class characteristics but not the individual rifling marks necessary for bullet-to-gun matching. High-velocity .223-caliber rifle bullets fragmented extensively within target tissues, causing severe wounding. Radiologic examination of resulting wounds showed images strikingly similar to the lead "snowstorm" picture caused by high-velocity hunting ammunition.

Animals↗
PubMed1998

Structure and refinement of the physical mapping of the gamma- glutamylcysteine ligase regulatory subunit (GLCLR) gene to chromosome 1p22.1 within the critically deleted region of human malignant mesothelioma.

Glutathione is a ubiquitous antioxidant in mammalian tissues. The first step of its synthesis is catalyzed by the glutamate-cysteine ligase (GLCL) which consists of a heavy, catalytic subunit and a light, regulatory subunit (GLCLR). Previous genetic analyses have revealed frequent losses of chromosome 1p22-->p21 in human malignant mesothelioma and the shortest region of overlapping deletions has been narrowed between the two loci D1S435 and D1S236. An expressed sequence tag of the GLCLR gene was found within a YAC contig encompassing the same interval aoffwas therefore considered as a good candidate gene for predisposition to human mesothelioma. We report here the characterization of the genomic structure of the GLCLR gene and the refine its physical mapping to chromosome 1p22.1.

Base Sequence↗
PubMed1998

Relation between literacy, race, and stage of presentation among low-income patients with prostate cancer.

PURPOSE: Diagnosis of advanced prostate cancer is a major health problem, especially among low-income men. Opportunities vary for early detection of prostate cancer for low-income black and white men because of financial, cultural, and social factors. In this study, we evaluated the association of poor literacy skills with higher rates of presentation of advanced stages of prostate cancer among low-income black and white men who received care in equal-access medical systems. PATIENTS AND METHODS: Literacy and stage at diagnosis of prostate cancer were evaluated in 212 low-income men who received medical care in Shreveport, LA, and Chicago, IL. The patients' literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine (REALM), an individually administered reading screening test designed specifically for use in the medical setting. Logistic regression models were used to evaluate predictors of metastatic disease at presentation as a function of patient age, race, literacy, and city. RESULTS: Whereas black men were almost twice as likely to present with stage D prostate cancer (49.5% v 35.9%; P < .05), they were significantly more likely to have literacy levels less than sixth grade (52.3% v 8.7%; P < .001). However, after adjustment for differences in literacy, age, and city, race was not a significant predictor of advanced-stage prostate cancer. CONCLUSION: Low literacy may be an overlooked but significant barrier to the diagnosis of early-stage prostate cancer among low-income white and black men. The development of culturally sensitive, low-literacy educational materials may improve patient awareness of prostate cancer and improve the frequency of diagnosis of early-stage cancer.

Adult↗
PubMed1998

Effect of pramipexole in treatment of resistant restless legs syndrome.

OBJECTIVE: To report the results of an open-label trial with a dopaminergic agent, pramipexole, in patients with treatment-resistant restless legs syndrome (RLS). MATERIAL AND METHODS: We studied the response to pramipexole in a consecutive series of 16 patients with symptomatic RLS who had previously experienced failure with other dopaminergic therapies. Patients assessed their posttreatment change in symptoms of RLS on a visual analog scale and indicated drug-related side effects with use of a checklist. RESULTS: With a mean dose of pramipexole of 0.3 mg, most patients reported clinically significant improvement. From 2 to 3 months after initiation of pramipexole therapy, nocturnal leg restlessness, involuntary leg movements, and insomnia had decreased in 12, 10, and 11 patients, respectively. The most frequent adverse effects were fatigue and stiffness, which occurred in a third of the patients. Overall, the drug was well tolerated. CONCLUSION: On the basis of these findings, we propose that pramipexole, a D2 subgroup receptor agonist, is an effective agent for treatment of RLS.

Adult↗
PubMed1998

The role of postmortem examination in medical education.

Historically, the postmortem examination was an indispensable diagnostic tool. Despite recommendations by the American Medical Association to continue performing autopsies, many physicians and medical institutions fail to recognize its utility in modern medicine, and autopsy rates have decreased to unacceptably low levels. In academic settings, requesting consent for autopsies is the responsibility of residents, who often lack the skills necessary to approach the grieving family, request consent, and follow up the autopsy results. Additionally, the information obtained at autopsies is often unused or is unavailable to families and clinicians. In order to improve the autopsy rate and enhance its clinical and educational benefits, the training of residents must be structured to emphasize the postmortem examination and to develop a standardized means of communication among clinicians, pathologists, and families.

Autopsy↗