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Biomedical subjects

M Spitz

Publications and source records attributed to M Spitz.

At least 19 recordsLinked to original sources

Ovarian expression and function of neuropeptide systems in teleosts and anurans.

The hypothalamic-pituitary-gonadal axis regulates reproduction, sexual maturation, and spawning behaviours. Its evolutionary origins trace back to primitive jawless fish and has been well characterized in teleosts. Recent advances in multi-species genome sequencing, annotation, and experimental approaches for identifying and characterizing key regulators have advanced understanding of neuroendocrine regulation in teleost reproduction, reshaping existing models. Early studies in amphibians established that steroids are critical regulators of final oocyte maturation. Subsequent work in anurans revealed complex interactions among theca cells, follicular cells, and oocytes, supporting a three-cell model in which oocytes contribute to their own steroidogenic environment, challenging the traditional two-cell view of ovarian steroidogenesis. In teleosts, however, direct evidence that oocytes support steroid precursor delivery to theca and follicular cells is limited, and whether a comparable three-cell model applies remains an open hypothesis. Across both taxa, the roles of locally produced neuropeptides in coordinating interactions among theca cells, follicular cells, and oocytes remain largely uncharacterized. Here, we provide a short review of the localization and potential autocrine/paracrine functions of neuropeptides in teleost and amphibian ovaries and discuss existing knowledge gaps. We identify opportunities to leverage detailed localization studies that map neuropeptides to specific ovarian cell types and developmental stages, and discuss how integrating traditional and emerging experimental approaches can advance comparative studies in ovarian endocrinology. This work will improve our understanding of reproductive regulation in fishes and frogs, with applications in captive breeding, aquaculture, and endocrine disruption research.

Autocrine↗

New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine.

OBJECTIVE: To determine the relative tolerability and efficacy of two newer antiepileptic drugs, lamotrigine (LTG) and gabapentin (GBP), as compared to carbamazepine (CBZ) in older patients with epilepsy. METHODS: This was an 18-center, randomized, double-blind, double dummy, parallel study of 593 elderly subjects with newly diagnosed seizures. Patients were randomly assigned to one of three treatment groups: GBP 1,500 mg/day, LTG 150 mg/day, CBZ 600 mg/day. The primary outcome measure was retention in trial for 12 months. RESULTS: Mean age was 72 years. The most common etiology was cerebral infarction. Patients had multiple medical conditions and took an average of seven comedications. Mean plasma levels at 6 weeks were as follows: GBP 8.67 +/- 4.83 microg/mL, LTG 2.87 +/- 1.60 microg/mL, CBZ 6.79 +/- 2.92 microg/mL. They remained stable throughout the trial. Early terminations: LTG 44.2%, GBP 51%, CBZ 64.5% (p = 0.0002). Significant paired comparisons: LTG vs CBZ: p < 0.0001; GBP vs CBZ: p = 0.008. Terminations for adverse events: LTG 12.1%, GBP 21.6%, CBZ 31% (p = 0.001). Significant paired comparisons: LTG vs CBZ: p < 0.0001; LTG vs GBP: p = 0.015. There were no significant differences in seizure free rate at 12 months. CONCLUSIONS: The main limiting factor in patient retention was adverse drug reactions. Patients taking lamotrigine (LTG) or gabapentin (GBP) did better than those taking carbamazepine. Seizure control was similar among groups. LTG and GBP should be considered as initial therapy for older patients with newly diagnosed seizures.

Aged↗

Hemicrania continua postpartum.

Hemicrania continua is a common, but unrecognized headache disorder. We describe two patients with hemicrania continua whose symptoms started in the postpartum period, coined as hemicrania continua postpartum.

Adult↗

Consensus statements from the Second International Lung Cancer Molecular Biomarkers Workshop: a European strategy for developing lung cancer molecular diagnostics in high risk populations.

The Second Molecular Biomarkers Workshop was held at the Roy Castle International Centre for Lung Cancer Research in Liverpool, in June 2001 and it brought together experts in the clinical, epidemiological and molecular-pathology of lung cancer from Europe and the USA, to address issues surrounding the development of a European strategy for early lung cancer detection. The 2001 Workshop Breakout Groups concentrated on the current challenges in the early detection of lung cancer which need to be addressed in the light of the recent surge in interest in many countries for mounting new clinical trials to evaluate the utility of Spiral CT in early lung cancer detection. If population-based trials of CT screening are mounted it will also be a favorable clinical environment in which to evaluate efficiently recent advances in molecular screening and genotyping. The Workshop focused specifically on: a) clinical and molecular biomarkers, b) sputum as an early detection and diagnostic tool, c) validation of molecular markers prior to their use in early detection trials and d) ethical issues that have to be considered in early lung cancer detection trials. A distillation of the Workshop discussions is given in this article.

Biomarkers, Tumor↗

Single-shot plasmid DNA intrasplenic immunization for the production of monoclonal antibodies. Persistent expression of DNA.

Monoclonal antibodies (Mc. Abs.) were generated against a 18-kDa protein from Brucella abortus 48 h and 25 days after a single intrasplenic injection of a DNA plasmid containing the expression vector for the protein. Hybridomas were also obtained from spleens injected 3, 5, and 10 days before fusion. Somatic cell fusion of spleen cells from mice, injected with the plasmid DNA, in saline, with the NS-0 myeloma cell line resulted in Mc. Abs of the IgG and IgM Isotypes. IgG antibodies were of the IgG2b and IgG1 subtype. Hybridoma tissue culture supernatants were strongly positive by ELISA at dilutions of up to 1/1200 and produced intense specific bands in immunoblotting. All these antibodies recognized the native recombinant protein (the screening antigen) and some of them also recognized the heat-denatured recombinant 18-kDa protein. When compared to standard procedures of immunization, as well as to intramuscular or gene gun DNA immunizations, this technique results in very early, time saving, strong Mc Abs. It is common knowledge that in order to generate specific hybridomas; spleen cells from immunized animals have to be fused no later than 5 days after the last boost. The fact that through single-shot intrasplenic immunization (SSI) specific hybridomas are generated 25 days after one single injection indicates that the gene coding the p18 protein is being expressed in the spleen for at least 20 days. We propose that plasmid DNA intrasplenic immunization can be a helpful tool for the production of specific hybridomas. This route of immunization could also be helpful in the further understanding of early events of the immune response to genetic immunization by naked DNA injection.

Animals↗

Effects of combined superoxide dismutase and catalase on somatosensory evoked potentials and neuropathologic changes in asphyxiated newborn lambs.

The lamb model of neonatal asphyxia has been used to describe changes in cerebral blood flow, oxygen metabolism and mitochondrial function following a standard asphyxial insult. In addition, abnormalities in cerebral hemodynamics and mitochondrial function after asphyxia have been associated with injury mediated by oxygen free radicals. The purpose of this investigation was to describe changes in brainstem auditory and somatosensory evoked potentials and pathologic changes after asphyxia in the newborn lamb. In addition, the hypothesis that treatment with the oxygen free radical scavenging enzymes superoxide dismutase and catalase would enhance postasphyxia recovery of evoked potentials and ameliorate pathologic injury was tested. Electrophysiologic and pathologic abnormalities after asphyxia were demonstrated, but treatment with oxygen radical scavengers had no effect on these abnormalities.

Animals↗

[Naked DNA vaccines].

Although still in a developmental stage, naked DNA vaccines are already the most important advancement in the history of vaccinology. Both the injection of plasmid DNA in experimental animals by different routes and preclinical studies, demonstrate the induction of protective immunity against different pathogens. Therapeutic application of DNA vaccines are well under way. In spite of the growing understanding about methods and routes of immunisation, both the early mechanisms by which DNA dependent immunisation occurs as well as the transfected cell types remain poorly understood. There is abundant experimental evidence that myocytes, keratinocytes and dendritic cells play an important role in the induction of the immune response. There is also an ongoing controversy on the relative importance of each one of these cell types. The aim of this paper is to review the current state of affairs regarding the understanding of the cell types participating in an immune response to the injection of a plasmid DNA vaccine. It is probably unlikely that only one and the same cell type would be the transfected cell and the one presenting the immunising peptide on MHC class II and I. An important step towards the understanding of DNA immunising mechanisms would be to elucidate plasmid DNA transfection. Is there a cell type that has specific receptors capturing the plasmid, expressing it and transferring its products to the antigen-presenting cell?

Muscle, Skeletal↗

Case-control study of diet and prostate cancer in China.

INTRODUCTION: A higher incidence of prostate cancer is observed in the Western world than in Asian countries. Although it is relatively rare in China, an increased incidence has been reported in recent years. Studies in high-risk populations have suggested that dietary fat may play a role in enhancing the risk of developing prostate cancer. However, limited epidemiologic study has never examined the role of diet in low risk populations. METHODS: A case-control study was conducted in 12 cities in China to evaluate the relationship between dietary factors and prostate cancer risk. We conducted personal interviews with 133 histopathologically confirmed prostate cancer cases diagnosed between 1989 to 1992 and 265 neighborhood controls of similar age. RESULTS: Cases were more likely than controls to consume food with high fat and from animal sources (p < 0.01). The daily fat intake and the percentage of energy from fat were statistically significantly higher among cases than among controls (p < 0.01). The adjusted odds ratio for total fat between lowest quartiles and highest quartiles was OR = 3.6 (95 percent C.I. 1.8-7.2); for saturated fat, OR = 2.9 (95 percent C.I. 1.5-5.7); and for unsaturated fat, OR = 3.3 (95 percent C.I. 1.7-6.3). DISCUSSION: The data suggest that dietary fat, both saturated and unsaturated, are associated with an increased risk for prostate cancer in a low risk population.

Adult↗

Assessing the burden of cancer in Texas using vital statistics data.

BACKGROUND: Vital statistics data were used to describe the burden of cancer in Texas. METHODS: Average annual age-adjusted mortality data in Texas (1986 to 1990) for 17 cancer types were compared with the US data for whites and blacks and with California data for Hispanics. Trends were examined from 1980 to 1990 for the entire state and from 1976 to 1989 for 24 geographic regions within the state. RESULTS: Mortality excesses were detected for lung and liver cancer, and deficits for colorectal, breast, and prostate cancers. Rates were generally stable from 1980 to 1990 with several exceptions (lung, liver, colon). Six areas of Texas, including four areas along the Gulf Coast, had relatively more excesses of various cancers, without a discernible pattern by cancer type. CONCLUSIONS: Overall, Texas has fared favorably in cancer mortality when compared with the United States. Enhanced evaluation of the frequency of cancer, as well as the conduct of etiologic research, must await the availability of statewide long-term cancer incidence data.

Black or African American↗

Hypothetical mechanisms for the cellular and neurophysiologic basis of secondary epileptogenesis: proposed role of synaptic reorganization.

This review article evaluates the hypothetical cellular mechanisms responsible for chronic lesion-induced epilepsy. Emphasis is given to particular clinical characteristics of secondary epileptogenesis: (a) a temporal latency, (b) the involvement of distant but related sites, and (c) irreversibility. Although loss of GABAergic inhibitory interneurons or increased excitatory input to these interneurons may contribute to epileptogenesis, several studies have provided evidence that inhibition is not depressed in epileptogenic regions and may actually be enhanced. Axonal sprouting, synaptic reorganization, and formation of new recurrent excitatory circuits have been proposed to account for the increased seizure susceptibility of temporal lobe epilepsy. Recent data support the hypothesis that local inhibitory circuits mask the multisynaptic excitatory interactions that are associated with mossy fiber sprouting in the dentate gyrus and that physiological mechanisms that reduce inhibition or increase excitability unmask the new recurrent excitatory circuits responsible for seizures. A hypothesis based on axonal sprouting and synaptic reorganization can account for the essential clinical characteristics of secondary epileptogenesis and may have widespread applicability to the general phenomenon of lesion-induced epilepsy.

Animals↗

Cancer mortality among petroleum refinery and chemical manufacturing workers in Texas.

Epidemiologic historical cohort studies of petroleum refinery and chemical manufacturing workers in Texas were reviewed to examine their cancer mortality in comparison to the U.S. and to assess the possible impact of cancer mortality among these workers on the State of Texas as a whole. Summary standardized mortality ratios and 95% confidence intervals were calculated for 20 cancer types, taking into account the heterogeneity of individual studies. There were 4314 cancer deaths among the 92,318 workers employed in 10 independent plant populations. Overall, there was a significant deficit in cancer mortality among petrochemical workers compared with the general U.S. population (SMR = 88, 95% CI = 80 to 96). Only the summary SMRs for brain cancer (SMR = 113, 95% CI = 96 to 133) and leukemias (SMR = 112, 95% CI = 94 to 130) approached statistical significance. Lung and liver cancer mortality excesses, noted for Texas as a whole, were decreased in these workers. Additional follow-up of these cohorts, their expansion to include minority and female workers, and additional study of possible occupational contributions to leukemia and brain cancer are recommended.

Chemical Industry↗

Susceptibility to lung cancer in light smokers associated with CYP1A1 polymorphisms in Mexican- and African-Americans.

The gene-environment associations between potential carcinogenic agents modified by polymorphisms in the cytochrome P450 1A1 (CYP1A1) gene and lung cancer risk were assessed in a hospital-based case-control study composed of African- and Mexican-Americans. The study involved 171 cases and 295 controls identified from the greater Houston and San Antonio metropolitan areas. Both the exon 7 and MspI polymorphisms were analyzed by RFLP of PCR-amplified DNA, and in addition, the African-American-specific polymorphism was assayed for subjects who reported that they were African-American. Logistic regression analysis was performed to assess the association between each of the CYP1A1 polymorphisms and lung cancer, adjusting for the matching variables (age, sex, ethnicity) and other potential risk factors. Interactions between pack-years smoked, CYP1A1 genotypes, and case status were also evaluated. The variant allele frequencies did not differ by case status, but the distributions of genotypes were strikingly different by ethnicity. In addition, both the exon 7 and MspI polymorphisms, but not the African-American-specific polymorphism, were modified by the amount of cigarette consumption measured in pack-years. An approximate 2-fold increase in lung cancer risk among individuals with one or more of the variant alleles was observed among light smokers (defined as having smoked < or = 30 pack-years). The respective risk ratios for the exon 7 and MspI polymorphisms were 2.26 (95% confidence interval, 0.82-6.26) and 2.03 (95% confidence interval, 1.03-4.01) at low smoking dose. No such increase in risk was found among heavy smokers (> 30 pack-years). This phenomenon at low smoking dose was also observed when the two common polymorphisms were combined, which resulted in was a progressive increase in risk with an increasing number of variant alleles. These results indicate that at low smoking levels, the MspI and exon 7 CYP1A1 genetic polymorphisms confer susceptibility to lung cancer.

Adult↗

Epidemiology, biology, and chemoprevention of aerodigestive cancer.

Cancers of the aerodigestive tract are a major cause of worldwide morbidity and mortality. Long term survival rates for these epithelial cancers have not improved substantially in the past 20 years despite intensive efforts to improve the prevention and therapy of these diseases. Therefore, new approaches are needed. One new investigative approach is chemoprevention, the chemical prevention of cancer. Chemoprevention studies in the upper aerodigestive tract have focused on the reversal of premalignant lesions and the prevention of second primary tumors. These chemoprevention efforts have resulted from an understanding of the multistep nature of epithelial carcinogenesis and the diffuse epithelial injury that results from carcinogen exposure. Ongoing research efforts are attempting to define these processes. The interaction between carcinogen exposure and host susceptibility in the development of cancers of the aerodigestive tract is being evaluated (e.g., with an assay of chromosomal sensitivity to the clastogen bleomycin). This review discusses several new aspects of the epidemiology, biology, and chemoprevention of aerodigestive tract carcinogenesis.

Biomarkers, Tumor↗

Vasectomy and prostate cancer risk in China.

Vasectomy has been reported to be associated with an increased risk of prostate cancer in western countries. A hospital-based case-control study was conducted in 12 cities in China to evaluate the relationship between vasectomy and prostate cancer risk in China, a low-risk country with rising incidence and increasing use of vasectomy. Interviews were conducted with 138 histologically confirmed prostate cancer cases diagnosed during 1989-1992 and 638 controls (158 hospital cancer, 158 hospital noncancer, and 322 neighborhood controls) of similar ages. Vasectomy at least 10 years prior to interview was reported by 10% of the cases versus 3% of the controls. Odds ratios for prostate cancer associated with vasectomy were 2.0 (95% confidence interval, 0.7-6.1), 3.3 (95% confidence interval, 1.0-11.3), and 6.7 (95% confidence interval, 2.1-21.6), respectively, when hospital cancer, hospital noncancer, and neighborhood controls were used for comparison. Although detection bias is of concern, the data suggest that in China, men with a history of vasectomy may experience an increased risk of prostate cancer.

Aged↗

Monoclonal antibodies to crosslinked fibrin degradation products (XL-FDP). I. Characterization and preliminary evaluation in plasma.

Monoclonal antibodies (mabs) were raised against X-oligomers, the earliest soluble fragments released from crosslinked fibrin (XL-FN), by the action of plasmin. Two of the mabs (NIBn 52 and NIBn 123) were monospecific for X-oligomers in that they showed no binding to fibrinogen, the plasmic fragments of fibrinogen (D and E) and non-crosslinked fibrin (X, Y, D and E), or the terminal digestion product of XL-FN, fragment DD-E. One other mab (NIBn 178) was panspecific for X-oligomers in that it exhibited a weak affinity for fibrinogen. The mabs were used to develop a two-site immunoradiometric assay (IRMA) and an enzyme-linked immunospecific assay (ELISA) which permitted the specific measurement of X-oligomers directly in plasma, rather than in serum. This immunoassay is a true assay of fibrinolysis as distinct from fibrinogenolysis and may be a potential aid in the diagnosis and evaluation of thrombosis. In preliminary studies, the assay detected low levels of X-oligomers in normal plasma and elevated levels in patients with disseminated intravascular coagulation.

Antibodies, Monoclonal↗

Studies on the human basophil IgE receptor. Generation and characterization of monoclonal antibodies against the receptor.

Anti-human basophil IgE receptor (Fc epsilon R) monoclonal antibodies (McAbs) were generated and characterized. The production of these antibodies was facilitated by both a single step procedure for the enrichment of basophils using Ficoll-Paque centrifugation and a double staining technique combining the APAAP with alcian blue. By the double staining technique we could recognize the specific anti-basophil antibodies because the cells binding the antibody--APAAP positive cells--also had alcian blue-stained basophil granules. Blocking experiments showed that the McAb was directed against the Fc epsilon R since preincubation with human IgE blocked the binding of the McAb and preincubation with the antibody blocked the binding of IgE to basophils and inhibited the formation of IgE rosettes.

Animals↗

Single step enrichment of human peripheral blood basophils by Ficoll-Paque centrifugation.

A simple, rapid and economical method for the enrichment of basophils from peripheral blood with high recovery is described. Peripheral blood was layered over a Ficoll-Paque cushion and centrifuged. The Ficoll-Paque layer was aspirated taking care not to disturb the interphase and the buffy coat. The Ficoll-Paque layer contained most of the basophils. A recovery of 82% (65-95%) and a 23.5-fold enrichment of basophils with their morphology and biological activity preserved was achieved.

Antibodies, Anti-Idiotypic↗