Search PubMed⌕ Search

Biomedical subjects

A Joseph

Publications and source records attributed to A Joseph.

At least 127 records · Page 7Linked to original sources
PubMed1995

Evaluation of utilisation of health workers for secondary prevention of oral cancer in Kerala, India.

The utilisation of primary health workers (HWs) for cancer control in developing countries has often been suggested, based on the experience of feasibility studies in India and Sri Lanka. We initiated a project in 1988 to evaluate the long-term feasibility of using trained HWs in secondary prevention of oral cancer, to bring about earlier detection of oral cancer in the communities served by them. Two hundred and eighty-two HWs attached to 14 primary health centres (PHCs), serving approximately 0.92 million rural population in the northern half of Trivandrum district in Kerala, India, were trained in oral visual inspection to detect precancerous, malignant and other suspicious lesions of the oral cavity and refer them for confirmation and treatment. They were asked to examine subjects aged 35 years and above and to give person to person health education on tobacco in their target population. The HWs belonging to the PHCs serving approximately 1 million rural population in the southern half of Trivandrum district were not trained, and this region served as the control area. In addition to several process measures, stage distribution of oral cancer in subjects reporting from the intervention and control areas, as well as oral cancers referred by the HWs, as a proportion of total oral cancers from the intervention area, were the outcome measures evaluated. Only 9/282 (3.2%) trained HWs were motivated and they examined 17,812 eligible subjects in 3 years and referred 408 subjects with lesions; 258/408 (63.2%) referred subjects reported for further examination and ten oral cancers were detected among them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Familial microcephaly with severe neurological deficits: a description of five affected siblings.

Autosomal recessive microcephaly is usually characterized by normal developmental milestones and minor neurological deficits. In this report, we describe five siblings in one family with marked microcephaly, intractable seizures, quadriplegia and profound mental retardation. The recurrence risk of microcephaly when associated with devastating neurological deficits, as exemplified by this family, may be high and in such cases, the role of appropriate genetic counseling is of utmost importance.

Child↗
PubMed1995

Directional coronary atherectomy for the diagnosis and treatment of radiation-induced coronary artery stenosis.

While radiation therapy has been known to cause myocardial and pericardial damage, its role in accentuating coronary artery disease in the absence of traditional cardiovascular risk factors has been controversial. As younger patients with treatable cancers are being treated with mediastinal radiation, coronary artery disease as a cause for severe chest pain should be entertained as a possible diagnosis. We describe a 25-year-old male who presented with an inferior wall myocardial infarction 6 years after receiving mediastinal radiation and chemotherapy for Hodgkin's disease. He was subsequently treated by directional atherectomy to a 95% lesion in the right coronary artery. Histological examination of the atherectomy specimen revealed evidence of radiation-induced endothelial damage that had resulted in plaque formation and subsequent ischemia. Possible mechanisms for radiation-induced coronary artery disease and treatment options are discussed.

Adult↗
PubMed1995

The capsule and O antigen in Vibrio cholerae O139 Bengal are associated with a genetic region not present in Vibrio cholerae O1.

Vibrio cholerae O139 Bengal, although closely related to V. cholerae O1 El Tor, produces a polysaccharide capsule and has a distinct O antigen. We have identified a chromosomal region of at least 11 kb, as defined by three TnphoA mutations, that is required for the expression of both polysaccharides. Electron microscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis show that these TnphoA mutants have lost the abilities both to express capsule and to produce lipopolysaccharide beyond the core oligosaccharide. Reactivity with O139 typing serum and resistance to serum are also lost in the mutants. DNA probes for this region do not hybridize with O1 V. cholerae but do react with other vibrios, implying that the region was recently acquired.

Bacterial Capsules↗
PubMed1995

Preliminary structure determination of the capsular polysaccharide of Vibrio cholerae O139 Bengal Al1837.

Vibrio cholerae O139 Bengal has recently been identified as a cause of epidemic cholera in Asia. In contrast to V. cholerae O1, V. cholerae O139 Bengal has a polysaccharide capsule. As determined by high-performance anion-exchange chromatography and 1H nuclear magnetic resonance analysis, the capsular polysaccharide of V. cholerae O139 Bengal strain Al1837 has six residues in the repeating subunit; this includes one residue each of N-acetylglucosamine, N-acetylquinovosamine (QuiNAc), galacturonic acid (GalA), and galactose and two residues of 3,6-dideoxyxylohexose (Xylhex). The proposed structure is [formula: see text]

Bacterial Capsules↗
PubMed1995

Interleukin-1 alpha stimulates dopamine release by activating type II protein kinase A in PC-12 cells.

A recent study from this laboratory [A. R. Gwosdow, N. A. O'Connell, and A. B. Abou-Samra. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E461-E466, 1992] showed that the inflammatory mediator interleukin-1 alpha (IL-1 alpha) stimulates catecholamine release from primary cultures of rat adrenal cells. The present studies were conducted to determine whether 1) IL-1 alpha stimulates catecholamine/dopamine release from the adrenal medullary cell line PC-12 and 2) the adenosine 3',5'-cyclic monophosphate (cAMP)-protein kinase A (PKA) pathway is involved in IL-1 alpha-induced dopamine release from PC-12 cells. The results indicate that IL-1 alpha significantly (P < 0.05) elevated dopamine release after a 24-h incubation period. IL-1 alpha did not stimulate cAMP accumulation at any time period between 5 min and 2 h. In contrast, forskolin-treated cells elevated (P < 0.05) intracellular cAMP levels and increased dopamine release. Because IL-1 alpha did not affect cAMP accumulation, the effect of IL-1 alpha on PKA activity was investigated. IL-1 alpha increased (P < 0.05) PKA activity at 15 and 30 min and returned to control levels by 1 h. Forskolin also increased (P < 0.05) PKA activity. The type of PKA activated (P < 0.05) by IL-1 alpha was type II PKA. In contrast, forskolin activated (P < 0.05) type I and type II PKA. Inhibition of PKA with the PKA inhibitor H-8 blocked PKA activity and dopamine secretion by both IL-1 alpha and forskolin in PC-12 cells. These observations demonstrate that 1) IL-1 alpha stimulated dopamine release from PC-12 cells by activating PKA, 2) the mechanism of IL-1 alpha activation of PKA does not involve detectable increases in intracellular cAMP accumulation, and 3) IL-1 alpha activates type II PKA, which is used by IL-1 alpha to stimulate dopamine secretion from PC-12 cells.

Animals↗
PubMed1995

Six year neurodevelopmental follow-up of very low birthweight children.

Twenty-four children born preterm with very low birthweight (VLBW) in 1985 at Bikur Holim Hospital were followed until age 6 years. Their neurological status and developmental and cognitive abilities were examined at 1, 2 and 6 years of age respectively and were compared with a control group at age 6 years. Of the 24 VLBW children, 4 had major disabilities. Of those without major disabilities, mean total IQ (WPPSI) at six years was 101.5 +/- 11.3, not significantly different from their mean Mental Development Index (Bayley) at age 2 years which was 96.1 +/- 19.6, or from the mean total IQ of a control group of 6-year-old children which was 109.8 +/- 14.7. However, the mean verbal IQ of the VLBW children (95.3 +/- 11.7) was significantly lower than that of the control group (106.2 +/- 14.3) (P = 0.02). Minor neurological deficit was found in seven of the VLBW children and in only one of the controls (P = 0.05). These findings point to possible future learning difficulties and should alert both pediatricians and educationalists to the importance of long-term follow-up of VLBW children in order to identify and address their specific educational needs.

Case-Control Studies↗
PubMed1995

C substance--specific latex agglutination for early & rapid detection of Streptococcus pneumoniae in blood cultures.

A slide agglutination test was developed using latex particles coated with antiserum against the C substance, a common antigen for all serotypes of Streptococcus pneumoniae. This test was used for the rapid identification of pneumococci in blood culture broths which contained Gram positive cocci (GPC) in pairs or short chains on smear examination. Of 238 consecutive blood cultures with GPC tested, 72 were positive for Strep. pneumoniae by the latex test and conventional methods. The remaining 166 cultures were negative for both these, indicating a 100 per cent specificity and sensitivity for the test.

Antigens, Bacterial↗
PubMed1994

Central opioid receptor subtype mediation of isoproterenol-induced drinking in rats.

Opioid receptor subtype antagonists differentially alter different types of water intake such that mu2 receptors modulate deprivation-induced water intake, kappa receptors modulate hypertonic saline-induced water intake, and mu2, delta1 and kappa receptors modulate water intake following Angiotensin II (ANG II). Water intake stimulated by peripheral administration of the beta-adrenergic agonist, isoproterenol is attenuated by naloxone and is thought to be mediated by release of renin and production of ANG II. The present study examined whether systemic and i.c.v. administration of general opioid antagonists and central administration of specific opioid receptor subtype antagonists would selectively alter water intake following isoproterenol in rats. Both systemic (1 mg/kg s.c.) and central (1-20 micrograms) naltrexone reduced water intake induced by isoproterenol (25 micrograms/kg s.c.) over a 2-h period. The mu receptor antagonist, beta-funaltrexamine (B-FNA: 1-20 micrograms), but not the mu1 antagonist, naloxonazine (50 micrograms), dose-dependently reduced isoproterenol drinking. Both the kappa antagonist, nor-binaltorphamine (Nor-BNI, 5-20 micrograms) and the delta1 antagonist, [D-Ala2, Leu5, Cys6]-enkephalin (DALCE, 1-40 micrograms) also dose-dependently reduced isoproterenol drinking. These data implicate mu2, kappa and delta1 sites in the opioid modulation of isoproterenol drinking.

Animals↗
PubMed1994

Scatter factor modulates the metastatic phenotype of the EMT6 mouse mammary tumor.

EMT6 is a transplantable mouse mammary tumor cell line that has been utilized widely as a model system to study the effects of various treatments on local tumor growth and pulmonary metastasis. In this study, we examined the cellular mechanisms by which scatter factor (SF), a fibroblast-derived cytokine that stimulates epithelial cell motility, may contribute to tumor-cell dissemination, using the EMT6 model system. In vitro, SF stimulated EMT6 cell motility, invasiveness and cell-surface expression of urokinase (an enzyme required for cell migration through tissue). SF differentially stimulated EMT6 cell adhesion to and migration onto surfaces coated with collagen I and laminin. EMT6 cells treated in vitro with SF and injected i.v. into isogeneic BALB/c-Rw mice showed a small but significant increase (1.7-fold) in lung colony formation as compared with control cells. For EMT6 cells in vitro, SF had no effect on DNA synthesis, cell proliferation, cell size distribution, or in vitro colony-forming ability. Thus, the increase in lung colonization may be due to enhanced ability of SF-treated cells to adhere to subendothelial basement membrane or to invade through tissue. Studies of the tissue distribution of SF in BALB/c-Rw mice demonstrated high levels of active factor in the lung. Thus, the presence of endogenous pulmonary SF may have reduced the degree to which SF treatment stimulated EMT6 lung colonization. Significant SF activity was also found in extracts of EMT6 tumors. Cultured EMT6 cells did not produce SF, but did produce high titers of a soluble low-molecular-weight protein activity that is capable of stimulating SF production in human fibroblasts 3- to 5-fold. EMT6 tumor extracts contained high titers of a similar SF-inducing activity. These observations suggest that SF may contribute to the invasive and metastatic phenotype of EMT6 cells via a paracrine mechanism in which tumor cells induce the production of SF in stromal fibroblasts.

Animals↗
PubMed1994

Expression of scatter factor/hepatocyte growth factor is regionally correlated with the initiation of sperm motility in murine male genital tract: is scatter factor/hepatocyte growth factor involved in initiation of sperm motility?

Based upon findings that the scatter factor/hepatocyte growth factor (SF/HGF) has strong mitogenic and motogenic properties, and that the sperm cell acquires its fertilizing capacity and motility in the distal parts of mammalian epididymis, the present study was conducted to investigate the role of SF/HGF in initiation of sperm cell motility. This was investigated by determining the expression of SF/HGF in various regions of the murine male genital tract by scatter and cell tracking assays using MDCK epithelial cells, Western blot procedure, and the immunohistochemical procedure using paraffin sections of various regions of the male genital tract. The findings from all these assays indicate that SF/HGF is differentially expressed in various parts of the male genital tract with slight or no expression in the testes, caput epididymis, and vas deferens, and with the highest expression in cauda and corpus (distal) epididymis followed by expression in the corpus (proximal) epididymis. This region-specific SF/HGF expression pattern coincides with the pattern of acquiring the fertilizing capacity and motility by the sperm cell during its transit through the male genital tract. However, wherever SF/HGF was expressed in the male genital tract, its molecular weight was slightly higher (Mr, 82 kD), compared to the SF/HGF expressed in various other somatic tissues (Mr, 78 kD), indicating that the genital tract SF/HGF may be a different molecular species that shares some immunoreactive epitopes with the somatic cell SF/HGF. Incubation of immotile sperm from caput epididymis with the purified human placental SF/HGF of 78 kD initiated motility in 5-15% of sperm population. These results strongly suggest that the SF/HGF-like activity is expressed in the male genital tract in a region-specific manner, and this activity may have a role in initiation of sperm motility acquired during its transit through the epididymis in mammals.

Animals↗
PubMed1994

Clinical and angiographic variables affecting the progression of coronary artery disease as determined by quantitative angiography.

To assess by serial quantitative angiography, the significance of clinical and angiographic variables that affect the progression of coronary artery disease (CAD). Progression of disease by sequential angiography is unpredictable and the role of clinical risk factors controversial. Various intervention trials have demonstrated less progression and even regression in hyperlipidemic patients. Correlates of progression have included a younger age, unstable angina, and greater involvement of the coronary arteries, with few studies looking at angiographic features of individual lesions. Serial angiograms on 74 patients were analyzed by computer assisted quantitative angiography using absolute measurements. A total of 99 diseased segments were analyzed for progression defined as an absolute reduction of 20% in luminal cross-sectional area. A preliminary correlation coefficient was calculated for each of the clinical and angiographic variables to detect any association with progression, and the odds ratio determined. The presence of any of the clinical risk factors-diabetes, hypertension, serum cholesterol, smoking, and a family history of coronary disease could not predict progression. The use of beta blockers was three times less likely to be associated with progression (odds ratio 0.33). While the presence of distal disease was associated with progression of a more proximal lesion (odds ratio 2.4), eccentricity, branch point location, lesion length, calcification, thrombus, or the presence of collaterals did not influence progression of disease in an individual segment. In conclusion, the presence of any of the clinical risk factors could not predict progression of disease in an individual coronary segment as determined by serial quantitative angiography, and the use of beta blockers and the absence of coexistent distal disease was associated with less progression of disease in an individual coronary segment. This may be related to changes in wall stress, reduced platelet interactions, and the integrity and permeability of the vascular endothelium to lipids.

Adrenergic beta-Antagonists↗
PubMed1994

Acetaldehyde alters coagulation protein function.

Acetaldehyde is the first metabolite of ethanol and has the potential to react with proteins and alter their function. This study evaluated the function of clotting proteins that had been preincubated with acetaldehyde as compared to those incubated with buffer or ethanol as controls. Thrombin, fibrinogen, thromboplastin, or whole plasma were preincubated with 1.8-447 mM acetaldehyde, 1.7-429 mM ethanol, or buffer for varying time periods prior to use in a clotting assay. Clot formation was measured with an automatic fibrometer. Acetaldehyde prolonged the clotting time but ethanol did not. These experiments indicate that circulating acetaldehyde would have the potential to react with proteins of the clotting system and alter their function. Therefore, it is possible that not all of the abnormalities in coagulation in alcohol abusers result from inadequate hepatic synthesis. Perhaps some of the deranged coagulation may be the result of the interaction of acetaldehyde with coagulation proteins.

Acetaldehyde↗
PubMed1994

Effect of hepatocyte growth factor/scatter factor and other growth factors on motility and morphology of non-tumorigenic and tumor cells.

Using an automated cell analyzer system, the effect of hepatocyte growth factor/scatter factor (HGF/SF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), endothelial acidic fibroblast growth factor (a-FGF), platelet derived growth factor (PDGF), and recombinant human insulinlike growth factor (IGF) on the motility and morphology of Madin-Darby canine kidney (MDCK), rat hepatomas, C2, and H5-6 and murine mammary carcinoma (EMT-6) cells was investigated. Treatment of MDCK cells with HGF/SF, bFGF, EGF, and a-FGF resulted in an increase in average cell velocity and in the fraction of moving cells. Cells treated with the PDGF and IGF did not show significant alterations in velocity. MDCK cells treated with each growth factor were classified into groups of "fast" and "slow" moving cells based on their average velocities, and the average morphologic features of the two groups were quantitated. Fast-moving cells had larger average area, circularity, and flatness as compared to slow-moving cells. Factors that stimulated cell movement also induced alterations in cell morphologic parameters including spreading, flatness, area, and circularity. HGF/SF also scattered and stimulated motility of C2 and H5-6 hepatoma cells. In contrast to MDCK cells, there was no significant difference between the morphology of the fast moving and slow moving C2 and H5-6 cells. These studies suggest that growth factor cytokines have specific effects on motility of normal and tumor cells.

Animals↗
PubMed1994

Regulation of scatter factor production via a soluble inducing factor.

Scatter factor (SF) (also known as hepatocyte growth factor [HGF]) is a fibroblast-derived cytokine that stimulates motility, proliferation, and morphogenesis of epithelia. SF may play major roles in development, repair, and carcinogenesis. However, the physiologic signals that regulate its production are not well delineated. We found that various human tumor cell lines that do not produce SF secrete factors that stimulate SF production by fibroblasts, suggesting a paracrine mechanism for regulation of SF production. Conditioned medium from these cell lines contained two distinct scatter factor-inducing factor SF-IF activities: a high molecular weight (> 30 kD), heat sensitive activity and a low molecular weight (< 30 kD) heat stable activity. Further studies revealed that SF-producing fibroblasts also secrete factors that stimulate their own SF production. We characterized the < 30-kD SF-IF activity from ras-3T3 (clone D4), a mouse cell line that overproduces both SF and SF-IF. The < 30-kD filtrate from ras-3T3 conditioned medium induced four- to sixfold increases in expression of SF biologic activity, immunoreactive protein, and mRNA by multiple SF-producing fibroblast lines. Ras-3T3 SF-IF activity was stable to boiling, extremes of pH, and reductive alkylation, but was destroyed by proteases. We purified ras-3T3 SF-IF about 10,000-fold from serum-free conditioned medium by a combination of ultrafiltration, cation exchange chromatography, and reverse phase chromatography. The purified protein exhibited electrophoretic mobility of about 12 kD (reduced) and 14 kD (nonreduced) by SDS-PAGE. The identity of the protein was verified by elution of biologic activity from gel slices. Purified SF-IF stimulated SF production in a physiologic concentration range (about 20-400 pM). Its properties and activities were distinct from those of IL-1 and TNF, two known inducers of SF production. We suggest that SF-IF is a physiologic regulator of SF production.

3T3 Cells↗