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Biomedical subjects

S Martin

Publications and source records attributed to S Martin.

At least 127 records · Page 7Linked to original sources
PubMed2001

[Moderate alcohol consumption and cardiovascular diseases].

While excessive ethanol consumption can result in higher rate of morbidity and mortality resulting from several diseases including cancer and cirrhosis, epidemiological studies suggest that moderate alcohol ingestion reduces the risk of cardiovascular diseases. However, the precise mechanisms by which moderate alcohol consumption protects against coronary heart disease (CHD) is not fully understood. Epidemiological studies suggest that alcohol consumption influences several risk factors for CHD including blood pressure, plasma cholesterol levels, platelet function, and fibrinolytic parameters, preventing both vascular thrombosis and occlusion. Turning to molecular and cellular levels, ethanol has been shown to act on several signal transduction mechanisms involve in the inhibition of smooth muscle cells proliferation and migration and in the activation of the release of vasoactive factors from vascular cells such as nitric oxide (NO). The latter is of importance since NO has been shown to possess antioxidant, antiaggregant properties, to regulate vascular tone and to inhibit both proliferation of smooth muscle cells and adhesion of leukocytes. Altogether, the above mentioned beneficial properties of moderate concentration of ethanol might help to explain the cardio- and vascular protection induced by ethanol. This review compels several bibliographic data concerning the cardiovascular effect of moderate alcohol consumption.

Animals↗
PubMed2001

Scale-up of filamentous organisms from tubes and shake-flasks into stirred vessels.

The choice of small-scale fermentation systems contributes significantly to a successful scale-up. Creasing of flasks and the chosen shaker parameters influence the production of secondary metabolites in a strain- and even compound-specific manner. Using actinomycetes and fungi as model organisms the influence of the small-scale fermentation system on the production of various secondary metabolites is described and the effects on screening success and scale-up are considered.

Journal Article↗
PubMed2001

Expression of bcl-2, bax and bcl-xl in human gliomas: a re-appraisal.

We have analyzed the expression of the anti-apoptotic proteins bcl-2, bcl-xl and that of bax, a pro-apoptotic protein, in human WHO grade II astrocytomas (LGA) and WHO grade IV glioblastoma multiforme (GBM). Tumors were obtained immediately after surgical resection and were analyzed by immunohistochemistry (IHC), laser confocal microscopy (LCM) and immunoblots. Both IHC and immunoblot analysis indicated that the expression of bcl-xl was not significantly different between LGA and GBM. IHC indicated that the expression of bcl-2 was inversely correlated to the grade of the tumors (i.e more cells were bcl-2 positive in LGA than in GBM) while the expression of bax was unaffected by the grade of the tumor. In contrast, immunoblots revealed a parallel increase in the expression of bcl-2 and bax from the low to high grade tumor, suggesting a co-regulation of the expression of these two proteins during tumoral progression. Confocal analyses provide us with another possible level of complexicity in the regulation of apoptosis in these tumors, as these markers exhibited different subcellular localizations: bcl-2 was strictly associated with mitochondria and bcl-xl was present in both cytosolic and mitochondrial compartments while bax was found essentially in the cytosol of the tumoral cells. Taken together, our data suggest that the role of bcl-2 related proteins could be regulated at different levels in human astrocytomas (expression, subcellular localization, antigen exposure ...) which should be studied by different techniques.

Adult↗
PubMed2001

Horizontal gene transfer and host specificity of beta-haemolytic streptococci: the role of a putative composite transposon containing scpB and lmb.

Beta-haemolytic streptococci are important human and animal pathogens: their genetic traits that are associated with the ability to infect human hosts remain, however, unclear. The surface protein, Lmb, mediates the adherence of Streptococcus agalactiae to human laminin. For further analysis of the corresponding gene, the adjacent genomic regions were sequenced. Lmb is localized on a putative composite transposon of 16 kb and is flanked by two copies of a novel insertion sequence element (ISSag2). It harbours the genes scpB and lmb, which are 98% identical with the respective genes of Streptococcus pyogenes. Analysis of the distribution of these genes and ISSag2 among 131 streptococcal strains revealed that all of the human isolates, but only 20% (12 of 61) of the animal isolates, contained scpB and lmb or their homologues. To investigate if the putative transposon can be mobilized, an erythromycin resistance marker was incorporated into the lmb gene of S. agalactiae. Screening for mutant strains with a regained susceptibility for erythromycin identified strains with a deletion of scpB, lmb, and one copy of ISSag2. We hypothesize that a horizontal gene transfer caused the exchange of scpB and lmb and that the ability of S. pyogenes, S. agalactiae and group C and G streptococcal strains to colonize or infect human hosts is dependent on their presence.

Adhesins, Bacterial↗
PubMed2001

Onset of accumulation of PrPres in murine ME7 scrapie in relation to pathological and PrP immunohistochemical changes.

In a murine scrapie model, three different methods (immunohistochemistry, Western blotting and histoblotting) for determining disease-specific PrP accumulation were compared. The incubation period of ME7 scrapie in the F1 cross of C57 BL and VM/Dk mice is about 230 days. Mice show hippocampal neuronal loss from 160-180 days post-inoculation (dpi), CA1 neuron dendritic spine atrophy at 126 dpi, and axon terminal degeneration and synaptic loss from 84-98 dpi. Infectivity titres of at least 100 are present from 40 dpi. PrP was detected immunohistochemically at 60 dpi in the hippocampus and in the thalamus. Thus, PrP accumulation in the hippocampus precedes even the earliest neurodegenerative changes. Low amounts of PrP immunolabelling were found between 60 dpi and 126 dpi, after which the intensity increased markedly. The histoblot method detected PrPres in one of four mice at 100 dpi. Western blotting of whole brains first identified the PrPres at 80 dpi. Thus, in our hands, the most sensitive method for detecting disease-specific accumulations of PrP was immunohistochemical examination. However, immunohistochemical methods are unable to distinguish the normal and abnormal isoforms of PrP. It is therefore possible that the initial accumulation of PrP takes place as PrPsen and that the translation of PrPsen to PrPres does not take place until the later stages of the disease process. The accumulation of disease-specific PrP lags behind the development of infectivity titres. The relative rates of increase of infectivity titre and PrP accumulation are different, suggesting that these parameters may be measures of different biological events.

Animals↗
PubMed2001

Oral inoculation of sheep with the agent of bovine spongiform encephalopathy (BSE). 1. Onset and distribution of disease-specific PrP accumulation in brain and viscera.

Sixty-three Romney sheep aged 6 months, consisting of three groups (PrP(ARQ/ARQ), PrP(ARQ/ARR), and PrP(ARR/ARR)genotypes) of 21 animals, were infected orally with brain tissue from BSE-infected cattle. Sub-groups of the 21 PrP(ARQ/ARQ) animals were killed, together with uninfected controls 4, 10, 16, 22 or 24-28 (after the development of full clinical disease) months post-inoculation (mpi). One sheep from each of the two groups of four killed at 4 or 10 mpi were shown by immunohistochemical examination to possess disease-specific PrP accumulations in single lymph nodes. At 16 mpi, such accumulations were detected in two of four infected sheep in some viscera and in the spinal cord and brain. At 22 mpi, three of five infected sheep had widespread disease-specific PrP accumulations in all tissues examined, but the remaining two animals gave positive results only in the central nervous system. Clinical disease appeared at 20-28 mpi. Three sheep killed with advanced clinical signs showed widespread PrP accumulation in brain, spinal cord and peripheral tissues. These results confirmed that PrP(ARQ/ARQ) Romney sheep are susceptible to experimental infection with the BSE agent. The different sites at which initial PrP accumulations were detected suggested that the point of entry of infection varied. Once established, however, infection appeared to spread rapidly throughout the lymphoreticular system. The results suggested that in some BSE-infected sheep neuroinvasion occurred in the absence of detectable PrP accumulations in the viscera or peripheral nervous system. In contrast to cattle with BSE, however, most sheep showed disease-specific PrP accumulations in the lymphoreticular system. In this respect, BSE-infected resembled scrapie-infected sheep; it is possible, however, that future research will reveal differences in respect of targeting of cell types within the lymphoreticular and peripheral nervous systems. The PrP(ARQ/ARR)and PrP(ARR/ARR)sheep were also killed in sub-groups at intervals after inoculation. Up to 24 mpi, however, none of these animals showed disease-specific PrP accumulations. Further results will be reported later.

Administration, Oral↗
PubMed2001

Onset and distribution of tissue prp accumulation in scrapie-affected suffolk sheep as demonstrated by sequential necropsies and tonsillar biopsies.

Tonsillar biopsies (single or multiple) or necropsies, or both, were performed on sheep taken from a Suffolk flock in which frequent cases of scrapie had occurred over a period of several years. Clinically affected sheep of the susceptible PrP(AQ/AQ)genotype had widespread disease-specific PrP accumulation in the central nervous system (CNS), lymphoreticular system and peripheral ganglia. In nine healthy PrP(AQ/AQ)Suffolk sheep between 4 and 7 years of age, PrP could not be demonstrated post mortem in any of the lymphoreticular tissues, or in the peripheral ganglia or CNS. Tonsillar biopsies taken from animals of the resistant PrP(AR/AR)and PrP(AR/AQ)genotypes at age 3, 8, 14, 20 or 26 months did not show PrP accumulation. Disease- specific PrP accumulation in tonsillar biopsies from PrP(AQ/AQ)sheep was not seen in 20 animals aged 3 months, but was found in two of 10 animals at age 8 months and in eight of 10 animals at age 20 months. The numbers of PrP-positive tonsillar biopsies obtained from sheep previously biopsied on more than one occasion was greater than the number of positive tonsils obtained from other susceptible sheep of comparable ages. The earliest disease-specific PrP accumulation seen was in tingible body macrophages within germinal centres and only later was it detected in cells resembling follicular dendritic cells. Fourteen PrP(AQ/AQ)sheep examined post mortem at up to 17 months of age and which had not previously been biopsied or were biopsied only once had no CNS or tonsillar PrP accumulations. Two of these sheep subjected to necropsy at 14 months had PrP accumulation in lymphoreticular tissue, where it was confined to the mesenteric lymph nodes. In susceptible sheep, only low levels of immunohistochemically detectable PrP were present in a minority of follicles from tonsillar biopsies of young lambs, but by 14 months of age widespread PrP accumulation, affecting many or even all follicles, was present. Although clinical cases had widespread PrP accumulations in viscera, susceptible survivors had no such accumulations in tissues of the lymphoreticular system, peripheral nervous system or CNS, suggesting that some animals were not exposed to infection or were exposed to a non-infectious dose.

Animals↗
PubMed2001

Differential diagnosis of infections with the bovine spongiform encephalopathy (BSE) and scrapie agents in sheep.

Scrapie, bovine spongiform encephalopathy (BSE), and variant Creutzfeldt-Jakob disease belong to the group of disorders called transmissible spongiform encephalopathies or prion diseases. The possibility that some sheep may be infected with the BSE agent is of human and animal health concern. Immunohistochemical methods were used to identify specific prion protein (PrP) peptide sequences in specific cell types of the brain and lymphoreticular system (LRS) of sheep with natural scrapie and Suffolk and Romney sheep infected experimentally with the BSE agent. Clinically affected and some pre-clinical cases of BSE infection could be distinguished from scrapie cases by the lesser amount of labelling of PrP containing the 84-102 amino-acid peptide sequences in phagocytic cells of the LRS and brain. Additionally, BSE-infected sheep had higher degrees of intra-neuronal PrP accumulation in the brain, as detected by labelling for a range of PrP peptide sequences. These results suggest that there is strain-dependent processing of PrP in specific cell types within the nervous system and LRS which can be used to distinguish BSE- and scrapie-infected sheep.

Animals↗
PubMed2001

Low-density lipoprotein particle size, triglyceride-rich lipoproteins, and glucose tolerance in non-diabetic men with essential hypertension.

The aim of the study is to investigate serum lipoproteins abnormalities including low-density lipoprotein (LDL) particle size, and their relationship with other cardiovascular risk factors in men with essential hypertension. Plasma glucose and serum insulin levels during oral glucose tolerance test (OGTT), serum lipoprotein(a), apolipoprotein (apo) A-I. apo B. cholesterol and triglycerides in serum and in lipoproteins, and LDL particle diameter were measured in thirty-eight consecutive newly-diagnosed non-diabetic untreated hypertensive men and 38 healthy male controls. Plasma glucose at baseline, 60 and 120 min during OGTT was significantly higher in patients than controls whereas serum insulin levels did not differ between patients and controls. Serum apo B and triglycerides were significantly raised in patients compared with controls (1.08 +/- 0.17 g/L [mean +/- SD] vs 0.97 +/- 0.22 g/L. p < 0.05, and 1.56 +/- 0.90 mmol/L vs 1.15 +/- 0.57 mmol/L, p < 0.05, respectively). Very-low-density lipoprotein (VLDL) triglycerides and LDL-cholesterol were increased in patients compared with controls (0.89 +/- 0.79 mmol/L and 0.54 +/- 0.35 mmol/L, p < 0.05, and 4.08 +/- 0.85 mmol/L and 3.60 +/- 0.92 mmol/L, p < 0.05, respectively) whereas high-density lipoprotein (HDL) cholesterol was lower in patients compared with controls 0.95 +/- 0.22 mmol/L and 1.07 +/- 0.20 mmol/L, p < 0.05). Adjustment for body mass index, abdominal/hip perimeter ratio and area under the glucose curve did not attenuate the relationship between hypertension and VLDL-triglycerides. Six patients and two controls had a mean LDL diameter < or = 25.5 nm and in the former serum triglycerides ranged from 1.86 mmol/L to 2.37 mmol/L. Mean LDL particle diameter in both patients and controls showed an inverse relationship with log-transformed serum triglycerides (r = - 0.51, p < 0.001 and r = - 0.47, p < 0.005, respectively). Among patients, those with serum triglycerides > or = [corrected] 1.58 mmol/L had a lesser mean LDL diameter than those with triglycerides above this threshold (25.78 +/- 0.47 nm vs 26.30 +/- 0.35 nm, p < 0.001). Higher plasma glucose, serum apo B and LDL-cholesterol as well as the decrease in serum HDL-cholesterol in patients with hypertension are consistent with high coronary heart disease risk. Not only mild hypertriglyceridemia but also high-normal serum triglycerides in themselves or as a surrogate of a predominance of small dense LDL particles in plasma convey an additional risk for cardiovascular disease in hypertensive patients even though routine plasma lipids are within or near normal range.

Adult↗
PubMed2001

Profiles of patients who experienced a late acute rejection due to nonadherence with immunosuppressive therapy.

The purpose of this study was to determine the significance and patient profiles of nonadherence with immunosuppressive therapy in the etiology of late acute rejections (LARs), more than 1 year after heart transplantation. Nonadherence was assessed in 101 heart transplant recipients (14 females, 87 males) with a median age of 56 (Q1=50; Q3=61) and a median posttransplant status of 3 (range, 1-6) years, using electronic event monitoring and self-report. The influence of depression, perceived self-efficacy, knowledge, perceived health, symptom frequency and distress, perceived social support, and adherence with outpatient appointments on medication nonadherence was examined. Ten LARs occurring in six patients were observed. Nine of the rejections, emerging in five patients, appeared to be caused by medication nonadherence. Nonadherence with immunosuppressive therapy is a major risk factor in the etiology of LAR. Patient profiles allow the identification of patients at risk.

Adult↗
PubMed2001

Provider type and the receipt of general and diabetes-related preventive health services among patients with diabetes.

OBJECTIVE: Using a measure of provider type that includes "shared care" to determine the contribution of provider type on receipt of general and diabetes-related preventive health services. METHODS: Automated clinical and administrative data were used to identify adult patients with type 1 and 2 diabetes receiving care from a multispecialty, salaried group practice and enrolled in a large health maintenance organization between 3/97 and 2/98 (n = 10,991). Logistic regression models were fit using generalized estimating equation approaches to evaluate the contribution of provider type on service receipt. MEASURES: Preventive service receipt included receipt of glycated hemoglobin and lipid testing, retinal examinations, pneumococcal vaccines, Papanicolaou (Pap) smears, and mammograms. Multivariable analyses adjusted for age, sex, race, marital status, household income, diabetes-related comorbidities and complications, prescription drug use, laboratory testing results, and frequency of medical care contact. RESULTS: Patients seeing an endocrinologist and primary care physician (PCP) were more likely than those seeing endocrinologists alone to receive glycated hemoglobin testing (OR, 1.42), lipid testing (OR, 1.72), mammograms (OR, 2.12), and Pap smears (OR, 2.36), and more likely than those seeing PCPs alone to receive glycated hemoglobin testing (OR, 1.79), lipid testing (OR, 1.54), retinal examinations (OR, 1.33), and mammograms (OR, 1.43). Compared with patients seeing PCPs only, patient's seeing endocrinologists only were more likely to receive retinal examinations (OR, 1.37) and less likely to receive Pap smears (OR, 0.46). CONCLUSIONS: Care delivered by no one single provider type is associated with greater receipt of all recommended services. Instead, patients seeing both an endocrinologist and a PCP are most likely to receive recommended services.

Adult↗
PubMed2001

Effects of dehydration and rehydration on EMG changes during fatiguing contractions.

PURPOSE: This study measured the effects of sauna-induced dehydration (Dhy) and the effectiveness of rapid rehydration on muscle performance and EMG frequency spectrum changes associated with fatigue during isometric contractions. METHODS: Knee extensor muscle strength during isometric maximal voluntary contraction (MVC) and endurance time at 25% and 70% of MVC (ET25 and ET70, respectively) were measured three times in 11 healthy male subjects, under euhydration conditions (Eu), after Dhy, and after rehydration following Dhy (Rhy). RESULTS: Dhy led to a decrease in body weight by 2.95 +/- 0.05%. No significant effect of the hydration status was shown on MVC values. A 23% decrease in ET25 was recorded during Dhy (P < 0.01), whereas ET70 only tended to decrease (-13%, P = 0.06). ET25 was higher during Rhy than Dhy (8%, P < 0.05) but remained lower than during Eu (-17%, P < 0.05). The EMG root mean square (RMS) increased earlier during Dhy than Eu. Opposite changes were shown for the mean power frequency (MPF) of EMG, and Dhy resulted in an accelerated fall in MPF. However, because ET25 decreased with dehydration, RMS and MPF changes were similar during Eu and Dhy when reported to normalized contraction time, exhaustion was thus associated with similar values of RMS and MPF for all conditions. RMS and MPF changes during Rhy showed an intermediate pattern between Eu and Dhy. CONCLUSIONS: Dhy induced an increase in muscle fatigue, associated with early changes in EMG spectral parameters. It is not clear whether these alterations could be attributed to biochemical modifications, and the role of increased perception of effort when subjects were dehydrated should be clarified.

Adult↗
PubMed2001

Evaluation of De-O-acetylated meningococcal C polysaccharide-tetanus toxoid conjugate vaccine in infancy: reactogenicity, immunogenicity, immunologic priming, and bactericidal activity against O-acetylated and De-O-acetylated serogroup C strains.

The polysaccharide capsule of serogroup C Neisseria meningitidis (MenC) has been integral to vaccine development. Licensed MenC vaccines contain the O-acetylated (OAc+) form of polysaccharide. Some MenC strains have de-O-acetylated (OAc-) polysaccharide, which may affect antibody specificity and functional activity when used in a vaccine. We evaluated an OAc-MenC conjugate-tetanus toxoid conjugate (MCC-TT) vaccine given concomitantly with whole-cell diphtheria-tetanus-pertussis, Haemophilus influenzae type b, and oral polio immunization in 83 infants at 2, 3, and 4 months of age. Serum bactericidal activities (SBA) against OAc+ and OAc- MenC strains and OAc+ and OAc- polysaccharide-specific immunoglobulin G (IgG) levels were evaluated. MCC-TT vaccine was well tolerated. All infants produced SBA titers of > or = 8 after a single dose at 2 months of age. The SBA geometric mean titer for OAc+ strain C11 increased from 2.7 (95% confidence interval [CI] 2.2 to 3.2) to 320 (95% CI, 237 to 432), 773 (95% CI, 609 to 982), and 1,063 (95% CI, 856 to 1319) after one, two, and three doses of MCC-TT, respectively. OAc- IgG levels were twice as high as OAc+ IgG levels after the primary series of MCC-TT vaccine, and the SBA was significantly higher against the OAc- MenC strain. Antibody responses to booster vaccination with either OAc+ MenC polysaccharide vaccine (MACP) or a fourth dose of MCC-TT at 14 months of age provided evidence of immunologic memory. The acetylation status of the booster vaccine influenced the specificity of the response, with significantly higher OAc- IgG levels and SBA after MCC-TT vaccine compared to MACP vaccine but similar OAc+ antibody levels. MCC-TT vaccine is highly immunogenic and primes for immunologic memory against OAc+ and OAc- MenC strains in infancy.

Antibodies, Bacterial↗
PubMed2001

Hereditary pancreatitis in North America: the Pittsburgh-Midwest Multi-Center Pancreatic Study Group Study.

BACKGROUND: Hereditary pancreatitis (HP) was defined on a clinical basis alone until the first cationic trypsinogen gene (PRSS1) mutation was discovered through the initial phase of the current Pittsburgh Midwest Multi-Center Pancreatic Study Group (MMPSG) HP study in 1996, making genetic testing available. AIM: To evaluate the regional distribution of HP in the United States, and to compare the study's gene mutation database with the pedigree databases to determine whether family history alone predicts the likelihood of detecting mutations in the cationic trypsinogen gene. METHODS: Probands of families with HP, familial pancreatitis and idiopathic chronic pancreatitis were recruited through referrals from MMPSG collaborating centers, other physicians and self-referral of patients who had learned of the study through the World Wide Web (www.pancreas.org). Pedigrees were constructed, detailed questionnaires were completed and a blood sample was drawn for each proband and participating family members. The birthplace and current location of each patient was recorded, DNA was analyzed for known mutations and the pattern of phenotype inheritance was determined from analysis of each pedigree. RESULTS: A total of 717 individuals were ascertained; 368 (51%) had clinical pancreatitis confirmed and the rest were primarily unaffected family members used for linkage studies. Forty-six clinically unaffected individuals were silent mutation carriers (11% of mutation-positive individuals). HP was most common in Minnesota, New York and the central mid-Atlantic states plus Kentucky and Ohio. One hundred and fifteen of 150 kindreds fulfilled the strict definition of an HP family, and 60 (52%) had PRSS1 mutations. Of the families with a detected mutation, 11% did not fulfill the clinical definition of an HP kindred. CONCLUSIONS: The distribution of HP within the United States shows major regional differences. The etiology of HP can be identified in a small majority of HP families through genetic testing. However, family history alone is not a good predictor of finding a mutation in the cationic trypsinogen (PRSS1) gene.

Databases, Factual↗
PubMed2001

Congenital toxoplasmosis.

Toxoplasma gondii, a parasite, has three modes of transmission: oral intake of raw or undercooked meat or contaminated fruits and vegetables, ingestion of materials contaminated with cat feces, and transplacental infection. The focus of this article is congenital toxoplasmosis, which is transmitted to the fetus across the placenta. When primary infection of the mother occurs during pregnancy, there is a 40 percent chance of fetal infection; rate of transmission and severity of infection are related to gestational age at the time of infection. The brain and retina are often affected, and there can be a wide range of clinical disease. Amniocentesis or cordocentesis provides the most accurate diagnosis. At birth, 80-90 percent of infants with congenital toxoplasmosis are asymptomatic. But further testing may reveal retinal and central nervous system abnormalities, and there is a risk of long-term sequelae. Chorioretinitis, hydrocephalus, intracranial calcifications, and convulsions are the typical presentation of classic congenital toxoplasmosis. Serology is the most common method of diagnosing neonatal infection, but more complex tests are also utilized. The prognosis for the untreated infant is poor; however, when antibiotic therapy is started early, the rate of sequelae is reduced significantly.

Animals↗