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Biomedical subjects

A Katz

Publications and source records attributed to A Katz.

At least 109 records · Page 6Linked to original sources

The effect of pyrazine odor on body weight and the weight of various organs in chicks (Gallus gallus domesticus).

Embryonic and posthatch long-term exposure to the odor of 2-methoxy-3-isobutyl-pyrazine (2M3IP) was examined for its potential physiological consequences as reflected in changes in BW and organ weights in domestic chicks (Gallus gallus domesticus). Experiments were run from Day 1 of incubation to the age of 3 wk with a total of 360 fertile chicken eggs. The experimental design consisted of four treatment groups: PP chicks were exposed to 2M3IP during both incubation and posthatch rearing; PC chicks were exposed to 2M3IP during incubation only; CP chicks were exposed to 2M3IP during rearing period only; CC control chicks were not exposed to 2M3IP. Chicks were weighed immediately after hatch and at 3 wk of age, when they were necropsied. Various organs (thyroid, adrenal, testes, comb, liver, spleen, abdominal fat, and the bursa of Fabricius) were removed and weighed. Body weights of both sexes in the PP group were reduced. This reduction was significant in males relative to both CP and CC groups and in females only relative to the CP group. Effects of 2M3IP exposure on the examined organs were as follows: in males, adrenal gland weight significantly increased in the PP group vs all other groups. No weight differences were found between the other inspected organs among the four treatments. In females, comb weight significantly decreased compared with the rest of the groups when 2M3IP exposure occurred during incubation (PC). Further investigation is needed to study the mechanisms that underlie the differential effects of pyrazine odor on male and female chicks.

Adipose Tissue↗

Role of radiation therapy in the management of cutaneous malignant melanoma.

Traditionally, cutaneous malignant melanoma is regarded as a radioresistant tumor. Recently, however, an increasing number of clinical studies have refuted this notion. The authors examined the role of radiation therapy in the palliative and/or adjuvant treatment of cutaneous malignant melanoma. The records of 69 patients with cutaneous malignant melanoma were reviewed. Twenty-five patients with extensive regional lymph node involvement received adjuvant radiation therapy after primary surgical treatment, and the remainder received palliative radiation therapy. The therapeutic significance of fraction size was analyzed. In the palliative radiation therapy group, the response rate was 52% with a fraction size < or = 300 cGy and 35% with a larger fraction size (p > 0.05, NS). Local regional control rates after adjuvant radiation therapy using conventional fractionation and larger fraction size were 87% and 82%, respectively (p > 0.05, NS). Radiation therapy is effective in the management of cutaneous malignant melanoma. It plays an important role in the palliation of metastatic disease and as an adjuvant treatment. No advantage in using a large fraction size over conventional dose schedules was found.

Adult↗

Uptake of glucose analogs reflects the rate of contraction of cultured myocytes.

The present study demonstrates that: a) adenosine and R-N6-(2-phenylisopropyl)-adenosine (R-PIA, A1 and A3 adenosine receptor agonist) inhibited [3H]deoxyglucose uptake or [3H]3-O-methyl-D-glucose uptake; b) sugar uptake reflects the rate of contraction in cardiac cultures; c) [3H]deoxyglucose uptake or [3H]3-O-methyl-D-glucose uptake are useful quantitative probes for beating rate evaluation. A 25-40% decrease in [3H]deoxyglucose uptake (p < 0.01) was obtained following 13-21 min treatment with 100 microM adenosine together with 1 microM dipyridamole or with 10 microM R-PIA, which inhibited spontaneous contractions. Adenosine (10 microM) attenuated spontaneous beating rate and inhibited approximately 55% of the [3H]deoxyglucose uptake following 22 h treatment (p < 0.01). 1 microM R-PIA also attenuated beating rate following either a short (1 min) or long (24 h) application and decreased [3H]deoxyglucose uptake by 20-30% (p < 0.01) during 0.5-24 h of treatment. A 157 +/- 9% and 205 +/- 11% increase (p < 0.01) in [3H]deoxyglucose uptake was obtained at 27 and 37 degrees C, respectively, compared with the uptake at 17 degrees C, which completely inhibited spontaneous contractions. Similar results [33 +/- 6% (p < 0.01) and 21 +/- 8% (p < 0.05) inhibition in [3H]deoxyglucose uptake] were obtained following 2 and 22 h of carbamylcholine treatment, respectively. This treatment also reduced spontaneous contractions. [3H] 3-O-Methyl-D-glucose uptake also decreased by 31 +/- 12% (p < 0.05) as a result of the arrest of contractions by adenosine. Elevations of 90 +/- 13% and 34 +/- 11% (p < 0.01) in [3H]deoxyglucose uptake were obtained following treatment with isoprenaline after 2 and 22 h application, respectively. It is concluded that adenosine and R-PIA inhibited [3H]deoxyglucose uptake or [3H] 3-O-methyl-D-glucose uptake in rat heart culture and that there is a linkage between the rate of cardiac contractions in culture and sugar uptake.

3-O-Methylglucose↗

Tailoring treatment for classical Kaposi's sarcoma: comprehensive clinical guidelines.

Classical Kaposi's sarcoma (CKS) is a rare indolent proliferative disease which is particularly prevalent among Jews of Ashkenazi and Mediterranean origin. To define guidelines for its comprehensive management, we conducted a retrospective analysis of 123 patients, focusing mainly on treatment modalities. The CKS-related mortality was 4% (5 patients). Of the 39 patients for whom observation only was the primary approach, 15 (38%) remained progression-free for 1-83 months (median, 4 months). Twenty-nine of the 52 (56%) patients who underwent surgery as the primary approach remained recurrence-free for 1-162 months (median, 15 months). Radiotherapy achieved an objective response in 74 courses (85%), including 50 (58%) complete responses. Symptomatic relief was reported in 95% of the patients. Vinblastine (27 series) achieved an objective response in 73% of series, including 22% complete responses. Multivariate analysis of time to progression with observation alone identified immunosuppression as the only significant independent factor that predicted disease progression. Our study suggests that observation alone may be sufficient for immunocompetent asymptomatic patients; symptomatic resectable lesions are suitable for simple excision; and more advanced disease or unresectable lesions require radiotherapy. If disease is extensive or the other approaches fail, chemotherapy is appropriate. Tailoring the treatment for CKS is an integrative process, requiring good understanding of the role of each available modality in the different clinical disease settings.

Adult↗

[Serotonin re-uptake inhibitors as primary therapy for carotid sinus hypersensitivity].

Carotid sinus syndrome is a well-recognized cause of unexplained syncope in older patients, and may, lead to significant morbidity due to trauma from falls. Dual chamber pacing has been shown to be effective in relieving symptoms due to bradycardia, but not due to vasodepressor response. We report an 84-year-old man with recurrent syncope due to carotid sinus hypersensitivity. He was treated only with a serotonin reuptake inhibitor and was symptom-free after 3 weeks of therapy. He has remained symptom-free for the past year.

Aged↗

Survivors of sexual abuse: clinical, lifestyle and reproductive consequences.

BACKGROUND: In recent years, an increase in the prevalence of sexual abuse of women has been reported in Canada and elsewhere. However, there are few empirical data on the extent of the problem in Canadian aboriginal populations. The authors investigated the presence of a reported history of sexual abuse and other health determinants in a sample of women attending a community health centre with a substantial aboriginal population. This allowed determination of whether reported sexual abuse and its associated demographic and health-related effects were different for aboriginal and non-aboriginal women. METHODS: A sample of 1696 women was selected from women attending a community health centre in a predominantly low-income inner-city area of Winnipeg for a cross-sectional survey designed to study the association between sexual behavior and cervical infections. The survey was conducted between November 1992 and March 1995 and involved a clinical examination, laboratory tests and an interviewer-administered questionnaire. A substudy was conducted among 1003 women who were asked 2 questions about sexual abuse. RESULTS: The overall response rate for the main study was 87%. Of the 1003 women who were asked the questions about sexual abuse, 843 (84.0%) responded. Among the respondents, 368 (43.6%) were aboriginal. Overall, 308 (36.5%) of the respondents reported having been sexually abused, 74.0% of the incidents having occurred during childhood. The prevalence was higher among aboriginal women than among non-aboriginal women (44.8% v. 30.1%, p < 0.001). Women who had been sexually abused were younger when they first had sexual intercourse, they had multiple partners, and they had a history of sexually transmitted diseases. In addition, non-aboriginal women who had been sexually abused were more likely than those who had not been abused to have been separated or divorced, unemployed and multiparous and to have used an intrauterine device rather than oral contraceptives. Aboriginal women who had been sexually abused were more likely than those who had not been abused to have been separated or divorced, unemployed and multiparous and to have used an intrauterine device rather than oral contraceptives. Aboriginal women who had been sexually abused were more likely than those who had not been abused to have had abnormal Papanicolaou smears. The proportion of smokers was higher among the abused women than among the non-abused women in both ethnic groups. INTERPRETATION: A history of sexual abuse was associated with other clinical, lifestyle and reproductive factors. This suggests that sexual abuse may be associated with subsequent health behaviors, beyond specific physical and psychosocial disorders. Aboriginal and non-aboriginal women who have suffered sexual abuse showed substantial differences in their subsequent health and health-related behaviours.

Adult↗

Rpp2, an essential protein subunit of nuclear RNase P, is required for processing of precursor tRNAs and 35S precursor rRNA in Saccharomyces cerevisiae.

RPP2, an essential gene that encodes a 15.8-kDa protein subunit of nuclear RNase P, has been identified in the genome of Saccharomyces cerevisiae. Rpp2 was detected by sequence similarity with a human protein, Rpp20, which copurifies with human RNase P. Epitope-tagged Rpp2 can be found in association with both RNase P and RNase mitochondrial RNA processing in immunoprecipitates from crude extracts of cells. Depletion of Rpp2 protein in vivo causes accumulation of precursor tRNAs with unprocessed introns and 5' and 3' termini, and leads to defects in the processing of the 35S precursor rRNA. Rpp2-depleted cells are defective in processing of the 5.8S rRNA. Rpp2 immunoprecipitates cleave both yeast precursor tRNAs and precursor rRNAs accurately at the expected sites and contain the Rpp1 protein orthologue of the human scleroderma autoimmune antigen, Rpp30. These results demonstrate that Rpp2 is a protein subunit of nuclear RNase P that is functionally conserved in eukaryotes from yeast to humans.

Endoribonucleases↗

Endomitosis of human megakaryocytes are due to abortive mitosis.

During megakaryocyte differentiation, the promegakaryoblast (immature megakaryocyte) increases its ploidy to a 2(x) DNA content by a poorly understood process called endomitosis. This leads to the formation of a giant cell, the megakaryocyte (MK), which subsequently gives rise to platelets. In this report, we show that endomitosis of human MKs is due to abortive mitosis. Human MKs were obtained by a two-step purification of CD34(+) blood or marrow precursors followed by in vitro culture in the presence of MK growth factors. Microscopic examination shows that a large number of centrosomes (up to 32) and centrioles are present in polyploid MKs. After nocodazole treatment, more than 20% of the MK are blocked in a typical pseudo-metaphase. Both spontaneous and nocodazole-induced endomitosis are associated with a breakdown of the nuclear envelope and possess a complex mitotic spindle composed of several asters. Spindle microtubules radiate from each aster, creating a spherical structure. At metaphase, expression of the kinetochore phosphoepitope recognized by the 3F3/2 antibody is lost, and the sister chromatids segregate moving toward the spindle poles. After limited segregation, the chromosomes decondense and the nuclear envelope reforms in the absence of cytokinesis, isolating all chromosomes in a single nucleus. It has been proposed that endomitosis could be due to an abnormal CDK1 activity or an absence of cyclin B1. Our results show that cyclin B1 can be detected in all MKs, including those with a ploidy of 8N or more. The cyclin B1 staining colocalizes with the mitotic spindle. Using flow cytometry, the level of cyclin B1 increased until 8N, but remained identical in 16N and 32N MKs. Cell sorting was used to separate the MKs into a 2N/4N and >4N population. Both cyclin B1 and CDK1 could be detected in the endomitotic polyploid MKs using Western blot analysis, and a histone H1 kinase activity was associated with immunoprecipitated cyclin B1. We conclude that endomitosis of human MKs is due to abortive mitosis, possibly due to alterations in the regulation of mitotic exit.

Antigens, CD34↗

Prognostic value of CA 19-9 levels in patients with carcinoma of the pancreas treated with radiotherapy.

PURPOSE: CA 19-9 has been identified as a tumor marker for pancreatic carcinoma and has been shown to have some utility in predicting outcome in surgically treated patients. The purpose of this study was to evaluate its usefulness as a prognostic indicator in patients treated with radiotherapy. MATERIALS AND METHODS: A retrospective review of all patients treated with radiotherapy of definitive intent (n = 104) for carcinoma of the pancreas at Fox Chase Cancer Center from 1980-1994 was undertaken. Patients were categorized into four groups: Planned preoperative radiation with resection (n = 25); planned preoperative radiation without successful resection (n = 35); postoperative radiation (n = 21); and radiation without planned resection (n = 23). For each group, except those treated without planned resection, median dose for external beam radiotherapy was 50.4 Gy (range = 21.6-63.0 Gy). Those in the remaining fourth group were treated with a median dose of 55.8 Gy (range = 36.0-60.4 Gy). 97% of patients in the first three groups were also treated with 5-FU-based chemotherapy, as were 61% of those in the fourth group. Pretreatment and follow-up CA 19-9 levels were available for 69 patients. RESULTS: Median survival time for all groups was 10 months (range = 1-67 months). Univariate analysis showed significant differences in survival among the groups: Preop with resection 22 months; preop without resection 10 months, postop 17 months; and without planned resection 12 months (p = 0.0005). Overall, patients who underwent resection had a median survival time of 19 months, compared to 11 months in those who did not (p = 0.0006). CA 19-9 level at diagnosis was found to be a significant prognostic indicator on univariate analysis, with a median survival time of 8 months in those having a level greater than the median of 680 U/ml, compared to 20 months in those who did not (p = 0.0003). Similarly, the posttreatment nadir was significant, with a median survival time of 11 months in those with levels above the median of 162.5 U/ml, vs. 26 months in those with levels below 162.5 U/ml (p = 0.001). The median survival time for patients whose CA 19-9 levels decreased in response to treatment by more than 75% was 23 months (range = 6-34 months) vs. 8 months (range = 3-21) in those with 75% or less response (p = 0.003). On stepwise multivariate analysis, pretreatment CA 19-9 level was found to be a significant predictor of survival (p = 0.005). Other potential indicators of outcome, including age, gender, KPS, prediagnosis weight loss, location of tumor, clinical TNM staging, size of lesion, vascular involvement on angiography, and sequence of radiation with respect to resection, were evaluated and were not found to be significant. CONCLUSION: CA 19-9 was demonstrated to be a useful prognostic indicator in patients treated with radiotherapy; other, more traditional, indicators of outcome were of less utility.

Aged↗

Interleukin-6 functions in autoimmune encephalomyelitis: a study in gene-targeted mice.

The encephalitogenic peptide pMOG 35-55 from the myelin oligodendrocyte glycoprotein was used to induce experimental autoimmune encephalomyelitis (EAE) in H-2b mice with the interleukin-6 (IL-6) gene intact or disrupted. The IL-6+/+ mice developed a chronic form of EAE ascending paralysis, whereas the IL-6-/- mice were resistant to the disease. Injections of recombinant IL-6 following pMOG immunization induced severe disease in the IL-6-/- mice. Histological examination of brain and spinal cord sections showed that the perivascular infiltration of inflammatory cells evident in IL-6+/+ mice was absent in the IL-6-/- animals and could be restored by exogenous IL-6 administration. Anti-MOG antibody levels were much lower in the IL-6-/- mice, but were not restored to high levels by IL-6 injections which elicited the development of pMOG 35-55-induced EAE. T lymphocytes reactive to the pMOG antigen were recovered from lymph nodes of both types of mice and Tcell lines could be established from both. Adoptive transfer of Tcell lines from IL-6+/+ mice induced EAE in the mice with the intact IL-6 gene but less in the IL-6-deficient mice, indicating that the resistant phenotype cannot be explained solely by lack of encephalitogenic Tcells. The absence of cell infiltrates in the brain and spinal cords of IL-6-/- mice upon adoptive transfer of the pathogenic Tcells from IL-6+/+ mice is consistent with a function of IL-6 in the local perivascular inflammatory process.

Adoptive Transfer↗

Induction of secretory phospholipase A2 confirms the systemic inflammatory nature of adjuvant arthritis.

Adjuvant arthritis (AA) is an accepted model of inflammatory arthritis. Until now, however, there is little information about inflammatory mediators, specifically in relation to the arachidonic acid cascade in AA. Our objective was to study the expression of secretory (sPLA2) and cytosolic (cPLA2) phospholipases A2 in various organs during the course of AA. AA was induced in Lewis rats which were sacrificed at days 0, 7, 14, 21, 28 and 42. Expression of sPLA2 mRNA and protein and mRNA of cPLA2 in paws, regional lymph nodes, spleen, liver, lungs and aorta was investigated. Serum sPLA2 activity increased from 15213 +/- 1131 to a maximum of 32,455 +/- 4109 nmol/30' on day 21. Maximal increase in sPLA2 mRNA in paws, lung and aorta was observed on day 14, and in the lymph nodes and spleen on day 28. In the liver, trace levels were found with no corresponding protein expression. In paws, lung, aorta and lymph nodes maximum increase in sPLA2 protein was noted on day 14 whereas the spleen showed constant sPLA2 protein level during AA. cPLA2 mRNA detected in all organs, did not significantly change during the course of AA, with the exception of regional lymph nodes where the message increased between 14 and 28 day. Induction of mRNA and protein of sPLA2 in several organs is an evidence that AA is a systemic inflammatory process. The parallelity of the sPLA2 expression to the severity of inflammatory process, implies that sPLA2 may play pathogenic role in AA. Lack of enhancement of cPLA2 mRNA may mean that this enzyme is either not induced in AA, or it increases earlier in the course of the inflammatory process.

Animals↗

Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats.

Postinjury recovery in most tissues requires an effective dialog with macrophages; however, in the mammalian central nervous system, this dialog may be restricted (possibly due to its immune-privileged status), which probably contributes to its regeneration failure. We circumvented this by implanting macrophages, pre-exposed ex vivo to peripheral nerve segments, into transected rat spinal cord. This stimulated tissue repair and partial recovery of motor function, manifested behaviorally by movement of hind limbs, plantar placement of the paws and weight support, and electrophysiologically by cortically evoked hind-limb muscle response. We substantiated these findings immunohistochemically by demonstrating continuity of labeled nerve fibers across the transected site, and by tracing descending fibers distally to it by anterograde labeling. In recovered rats, retransection of the cord above the primary transection site led to loss of recovery, indicating the involvement of long descending spinal tracts. Injection of macrophages into the site of injury is relatively non-invasive and, as the cells are autologous, it may be developed into a clinical therapy.

Animals↗

Classic Kaposi sarcoma: experience at Rabin Medical Center in Israel.

Classic Kaposi sarcoma is an indolent cutaneous proliferative disease affecting mainly elderly people of Mediterranean and Jewish origin. The authors review the epidemiologic and clinical findings in Israeli patients with classic Kaposi sarcoma treated at the Institute of Oncology, Rabin Medical Center. A total of 123 patients were identified. The average age at diagnosis was 68 years (range, 20-90 years) and, as expected, there was a strong predominance of men (2.4:1). All but two patients were Jewish. The distribution of Ashkenazic Jews and Sephardic Jews was almost equal. Twenty-three patients (19%) had secondary malignancies that were mostly solid tumors. The clinical course was indolent and rarely fatal (4% disease-related mortality). Multivariate analysis revealed that non-Ashkenazic origin, age over 70 years, multiple lesions (>10), and immunocompromised conditions adversely affected survival. Radiotherapy for localized skin lesions yielded an 88% objective response, with symptomatic relief in 95% of patients. Chemotherapy was similarly effective (76% response rate) in patients with disseminated disease. These data demonstrate the indolent nature of classic Kaposi sarcoma which usually requires a less aggressive therapeutic approach than in the African and AIDS-related types of Kaposi sarcoma.

Adult↗

IgA glomerulonephritis with irregular intramembranous dense deposits.

A 30-year-old white male presented with hematuria, proteinuria and normal renal function following a flu-like illness. IgA was mildly elevated but C3 and C4 levels were normal in serum. Renal biopsy showed a mesangial proliferative nephritis with immunohistochemical features of IgA nephritis but with an unusual pattern and distribution of deposits in glomerular, tubular and Bowman's capsular basement membranes.

Adult↗

neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group.

PURPOSE: It remains a challenge to predict which women with axillary node-negative (ANN) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer prognosis. Although overexpression has been investigated extensively, this study represents the first prospective assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN. METHODS: A consecutive series of women was monitored for recurrence (median follow-up duration, 36 months) and tumors from 580 individuals were analyzed for amplification. The association of amplification with risk of recurrence was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS: Neu/erbB-2 was amplified in 20% of cases. We found an increased risk of disease recurrence when neu/erbB-2 was amplified > or = twofold that persisted with adjustment for other prognostic factors (relative risk, 2.36; P = .002). We found some evidence that amplification was more important in patients who received chemotherapy compared with untreated patients. CONCLUSION: neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.

Axilla↗

Radiation therapy for rectosigmoid and rectal cancer: results of the 1992-1994 Patterns of Care process survey.

PURPOSE: To determine the US national practice standards for patients with adenocarcinoma of the rectum treated in radiation oncology facilities. MATERIALS AND METHODS: A national survey of 57 institutions identified 507 eligible patients who received radiation therapy as a component of their treatment for rectal cancer. A stratified two-stage cluster sampling with simple random sampling at each stage for each stratum was used and on-site surveys were performed. RESULTS: Of the 507 patients, 378 (75%) received postoperative therapy, 110 (22%) received preoperative therapy, 17 (2%) received both preoperative and postoperative therapy, and less than 0.5% received intraoperative radiation alone. To more accurately assess the utilization of modern radiation techniques as well as recommendations of the National Cancer Institute (NCI)-sponsored, randomized, postoperative, adjuvant combined modality therapy rectal cancer trials into current practice, the analysis was limited to the 243 (48%) patients with tumor, node, and metastasis staging system classification T3 and/or N1-2M0 disease who underwent conventional surgery with negative margins. Although only 7% were treated on a clinical trial, 90% received chemotherapy for a median of 21 weeks. Most were treated with modern radiation treatment techniques. In contrast, techniques to identify and help exclude the small bowel from the radiation field were not routinely used. CONCLUSION: Despite the fact that only 7% of patients with T3 and/or N1-2M0 disease were treated on a clinical trial, such trials appear to have resulted in a positive influence on the standard of practice within the oncology community. Although there are still some deficiencies, the majority of these patients received combined modality therapy and were treated with modern radiation therapy techniques.

Adenocarcinoma↗