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Biomedical subjects

M John

Publications and source records attributed to M John.

At least 235 records · Page 13Linked to original sources

Local arterial responses to 32P beta-emitting stents.

PURPOSE: 32P beta-emitting stents reduce neointimal growth in rabbit iliac arteries for at least 12 months after deployment but are associated with incomplete healing. The aim of this study was to quantitate arterial cellularity, with emphasis on the inflammatory response following radioactive stenting. METHODS: 32P beta-emitting stents were placed in rabbit iliac arteries and analyzed at 3 months (6 and 24 microCi), and 6 and 12 months (6, 24, and 48 microCi). Arterial cellular proliferation and cell densities of smooth muscle cells (SMC), mononuclear cells (macrophages and lymphocytes), and neutrophils (PMN) were determined. RESULTS: Total intimal cell density was greatest in control stents at all three time points, composed mostly of SMCs. SMC density associated with radioactive stents increased from 3 to 12 months but was significantly less than control nonradioactive stents. There was a 4-fold increase in cellular proliferation in the 24 and 48 microCi group vs. control stents. In the media, SMC density of radioactive stent groups was significantly reduced vs. control stents at all three time points, for all three activities. At 3, 6 and 12 months, there was a dose-dependent increase in intimal inflammatory cell density, which consisted mostly of macrophages. For 6-microCi stents inflammation peaked at 3 months and decreased thereafter. Inflammation for 24-microCi stents peaked at 6 months and then decreased at 12 months. Inflammation associated with 48-microCi stents remained high at 6 and 12 months. Focal atherosclerotic change was seen in 11% of stents in the 24-microCi group, and 37% and 50% in the 48-microCi group at 6 and 12 months, respectively. CONCLUSION: Intimal SMC density remains suppressed out to 12 months after placement of 32P beta-emitting stents. However, inflammation and cell proliferation remain increased and may potentially result in greater neointimal formation over time.

Animals↗

Structure of a genomic clone encoding biologically active human relaxin.

Relaxin is a peptide hormone synthesized in the corpora lutea of ovaries during pregnancy and is released into the blood stream prior to parturition. Its major biological effect is to remodel the mammalian reproductive tract to facilitate the birth process. Determination of the structure of human relaxin is thus a first step in opening up the possibility of clinical intervention in cases of difficult labour. However, the limited availability of human ovaries during pregnancy has prevented both direct amino acid sequence determination and isolation of cDNA clones obtained from relaxin producing tissue. Our approach has therefore been to screen directly for a human relaxin gene using an homologous porcine relaxin cDNA probe. We report here the successful identification of a genomic clone from which the structure of the entire coding region of a human preprorelaxin gene has been determined. Synthesis of biologically active relaxin has shown that the novel gene structure described herein codes for an authentic human relaxin. We believe this is the first successful synthesis of a biologically active hormone whose structure was predicted solely from the structure of a genomic clone.

Amino Acid Sequence↗

Demonstration of TGF-alpha-EGFR and EGF-EGFR autocrine loops and their relation to proliferation in complete hydatidiform moles (CHM).

Complete hydatidiform moles (CHM) are the most common form of gestational trophoblastic disease. The prevalence rate is much higher in the state of Kerala, India, than in other parts of the world. The biology and role of growth factors are not fully understood in these tumors. In this study, we have immunohistochemically evaluated the expression of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) along with their receptor, epidermal growth factor receptor (EGFR), and we have related them to the proliferative activity in normal placenta and CHM using the expression of proliferating cell nuclear antigen (PCNA) as the marker of proliferation. The results suggest activation of both EGF-EGFR and TGF-alpha-EGFR autocrine pathways in both types of tissues, with a predominance of the TGF-alpha-EGFR autocrine pathway in CHM. This is especially so in the more aggressive cases of CHM, the persisting group of diseases.

Case-Control Studies↗

Etiology of acute respiratory infections in children in tropical southern India.

Nasopharyngeal secretions and throat-swab specimens from 809 children less than 6 years old with acute respiratory infection were examined by culture and indirect immunofluorescence for the presence of virus or viral antigen. Blood was cultured for the presence of bacteria in selected cases of lower respiratory infection (LRI); pleural fluid also was cultured in cases of empyema. Viruses were detected in 163 (49%) of 331 children with LRI. Respiratory syncytial virus (RSV) was the commonest agent isolated (106 children). Other viruses isolated included parainfluenza viruses (36 children), adenoviruses (12), and influenza viruses (five). Outbreaks of infection due to RSV occurred during August through October. Pneumonia was the commonest LRI encountered (178 children). Among children with pneumonia, viruses were detected in 65 (37%) of 178 children, and bacteria were isolated from 27 (18%) of the 147 children for whom blood cultures were done. Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus were the common bacterial pathogens isolated. In cases of empyema and pyopneumothorax, S. aureus was the commonest organism isolated. There were 116 children with bronchiolitis, 83 (72%) of whom had viral infections; the majority of these children (81%) had RSV infection. Croup was uncommon (eight cases) and was caused mainly by parainfluenza viruses.

Acute Disease↗

Analysis of flowering time in ecotypes of Arabidopsis thaliana.

There exists variation in the timing of the initiation of flowering among different ecotypes of Arabidopsis thaliana. We have examined the basis of this variation between the early flowering Columbia (Col) ecotype and the late flowering ecotypes. Coimbra (Co-4), Geneva (Ge-2), and Zu-rich (Zu-0). In crosses of Col to Co-4, Ge-2, and Zu-0, the late flowering trait behaved as a single dominant gene the F1 plants were late flowering and in segregating F, populations a 3:1 ratio of late to early flowering plants was observed. This dominant gene resides in a region of chromosome 4 that contains a gene (FRIGIDA) conferring late flowering in certain other Arabidopsis ecotypes. Allelism tests indicate that the same genesis responsible for late flowering in Co-4, Ge-2. Zu-0, and the San Feliu (Sf-2) ecotype. These and previous results indicate that FRIGIDA accounts for much of the later flowering observed in various ecotypes of Arabidopsis.

Arabidopsis↗

Concentrations of serum albumin and nonesterified fatty acids in bovine aqueous humor with regard to the fatty acid sensitivity of bovine lens epithelial cells.

Concentrations of albumin and nonesterified fatty acids (FAs) have been determined in bovine serum and aqueous humor (AH) with regard to the FA-to-albumin molar ratio, which has been proved decisive for the FA cytotoxicity to bovine lens epithelial cells as described previously. In 6- to 7-month-old female calves the average albumin level was reduced 309-fold from 638 micromol/l in serum to 2.00 micromol/l in AH, in 72- to 84-month-old cows 405-fold from 632 to 1. 56 micromol/l, and in 12- to 18-month-old bulls 395-fold from 553 to 1.40 micromol/l. In 64% of the animals the albumin concentration in AH differed significantly between both eyes. The serum albumin values resulted in a Gaussian curve, but the frequency distribution for AH albumin values skewed to the right. Using an enzymatic method the concentrations of nonesterified FAs were determined in serum as well as in concentrated AH samples. In all animals investigated the molar FA-to-albumin ratio was higher in AH than in serum. The results are discussed in view of the assumption that unsaturated nonesterified FAs might be cataractogenic risk factors.

Aging↗

Functional aspects of vascular tenascin-C expression.

The arterial tenascin C expression in vivo and in vitro has been studied using immunohistochemistry. The functional relevance of localized tenascin C expression was assessed in vitro using various human cell types involved in the progression of vascular disease. Normotensive and hypertensive rats exhibited age-dependent patterns of vascular (aorta) tenascin expression, but the lumen-to-media-directed progression of tenascin induction was accelerated in hypertensive rats. Tenascin-rich neointimal lesions (spontaneous) were observed at branching sites of aorta from aged (80 weeks) hypertensive rats. Subendothelial tenascin foci contained lipid-laden smooth muscle cells and monocytes/macrophages. Medial tenascin foci encaged smooth muscle cells which synthesized DNA. Tenascin was expressed both in vivo and in vitro by endothelial and smooth muscle cells but not by monocytes/macrophages; angiotensin II, oxidized-low density lipoprotein and transforming growth factor beta 1 induced expression of tenascin transcripts and glycoprotein in vitro. Endothelial and smooth muscle cells, but not monocytes, adhered to tenascin substrata. Tenascin reduced focal adhesion integrity in confluent endothelial and smooth muscle cell cultures. Angiotensin II-induced migration of endothelial and smooth muscle cells was accompanied by tenascin deposition within extracellular matrix migration trails. Tenascin may function both as a defense against monocyte invasion and medial smooth muscle replication, as well as a substratum for directed endothelial and smooth muscle cell migration.

Animals↗

Damage control.

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Attitude of Health Personnel↗