Biomedical subjects

A Joseph

Publications and source records attributed to A Joseph.

At least 19 recordsLinked to original sources

PubMed1992

Scatter factor is a glycoprotein but glycosylation is not required for its activity.

Scatter factor (SF) is a protein produced by fibroblasts, smooth muscle cells, and human placenta which scatter cohesive epithelial cell colonies and increases cellular motility. SF bound to concanavalin A and other lectins with high affinity. SF could also be stained with a glycoprotein specific stain. Incubation of producer cells (N-ras-transformed 3T3), with tunicamycin homolog A1 did not have any significant effect on the secretory activity of SF. The treatment of SF with N- and O-glycanases as well as endoglycosidase H had no effect on its activity. However, treatment of target (Madin Darby canine kidney) cells with tunicamycin A1, abolished the scattering response. These studies suggest that scatter factor is a glycoprotein, but glycosylation is not required for its secretion or activity by the producer cells; however, glycosylation of proteins in the target cells is required for SF action.

3T3 Cells↗

PubMed1992

Binding of scatter factor to epithelial cell membrane protein: identification of its receptor.

Binding of scatter factor (SF) to the surface protein of Madin-Darby canine kidney (MDCK) cells was investigated. The factor has a specific affinity for membrane proteins of MDCK cells and could be purified 10-20-fold using a membrane protein-affinity chromatographic procedure. The binding was pH- and salt-dependent. The factor did not bind to columns prepared with membrane proteins from non responder cells or with bovine serum albumin. Further purification to homogeneity was achieved using reverse phase and immunoaffinity chromatography. The factor dissociated into 92, 62 and 34/32 kDa bands on SDS-PAGE under reducing conditions. A 230 kDa protein band, the receptor-SF complex, was observed when radiolabeled SF was crosslinked to surface proteins of MDCK cells and the complexes were subjected to electrophoresis. The binding of radiolabeled SF to the MDCK cells was decreased in presence of excess unlabeled SF. These observations suggest that the binding of SF to surface proteins of MDCK cells is specific and occurs predominantly to a 150 kDa protein.

Animals↗

PubMed1992

Neuronal lysosomal enzyme replacement using fragment C of tetanus toxin.

Development of a strategy for efficient delivery of exogenous enzyme to neuronal lysosomes is essential to achieve enzyme replacement in neurodegenerative lysosomal storage diseases. We tested whether effective lysosomal targeting of the human enzyme beta-N-acetylhexosaminidase A (Hex A; beta-N-acetyl-D-hexosaminide N-acetylhexosaminohydrolase, EC 3.2.1.52) can be obtained by coupling it via disulfide linkage to the atoxic fragment C of tetanus toxin (TTC) that is bound avidly by neuronal membrane. TTC-Hex A conjugation resulted in neuronal surface binding and enhanced endocytosis of enzyme as observed in immunofluorescence studies with rat brain cultures. In immunoelectrophoretic quantitative uptake studies, rat neuronal cell cultures contained 16- and 40-fold greater amounts of enzyme after incubation with TTC-Hex A than with nonderivatized Hex A. In cerebral cortex cell cultures from a feline model of human GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases), binding and uptake patterns of the enzymes were similar to those in the rat brain cell cultures. After exposure to extracellular concentrations of enzyme attainable in vivo, lysosomal storage of immunodetectable GM2 ganglioside was virtually eliminated in neurons exposed to TTC-Hex A, whereas a minimal effect was observed with Hex A. These findings demonstrate the usefulness of TTC adducts for effective neuronal lysosomal enzyme replacement.

Animals↗

PubMed1992

Effect of scatter factor and hepatocyte growth factor on motility and morphology of MDCK cells.

We investigated the effects of human placental scatter factor (hSF), mouse scatter factor (mSF) and recombinant human hepatocyte growth factor (HGF) on motility and morphology of individual Madin-Darby canine kidney cells using a computerized cell tracking system. All three factors increased the velocity of individual cells and the ratio of moving to stationary cells. Similarly, all three factors caused changes in morphologic features of cells, leading to increased area, flatness, and polarity. Increases in area and flatness but not polarity were slightly greater with HGF than with hSF or mSF. These results suggest that SFs and HGF have similar effects on motility and morphology of isolated epithelial cells.

Animals↗

PubMed1992

Inhibition of interleukin 2 receptor expression in normal human T cells by cyclosporine. Demonstration at the mRNA, protein, and functional levels.

In view of the importance of the IL-2 receptors in the expression of antiallograft immunity and the currently existing controversy regarding the effect of CsA on the induction of IL-2 receptors, we explored the effect of cyclosporine on the induction of interleukin-2 receptor alpha and beta in normal human T cells. The effect of CsA on the induction of IL-2 receptors was examined at the levels of mRNA expression (with the aid of the polymerase chain reaction), protein (by SDS-PAGE analysis of chemically crosslinked 125I-IL-2 membrane protein complexes and by FACS), and function (by Scatchard analysis of 125I-IL-2 binding to T cells). The T cells were signaled with sn-1,2-dioctanoylglycerol and ionomycin or with crosslinked anti-CD3 and anti-CD2 mAbs. Our experimental design revealed that (A) CsA inhibits the induction of IL-2 receptor alpha and beta in normal human T cells, (B) the inhibitory activity is realized by a direct effect on T cells, and (C) the inhibitory activity is detectable at the pretranslational level--CsA significantly reduced the induction of mRNA encoding IL-2 receptor alpha and IL-2 receptor beta. These observations together persuasively demonstrate the ability of CsA to interrupt the emergence of IL-2 receptors on the surface of normal human T cells.

Antibodies, Monoclonal↗

PubMed1992

The teaching of behavioural sciences.

Medical science over the last few decades has undergone vast changes. Technologically it has advanced at a rapid pace. There has been a realization as well that the behaviour of individuals and communities also influences the occurrence of disease. Medical schools around the globe have realized the need for incorporating behavioural sciences as an integral part of the basic sciences taught to medical students. This paper presents the experience of Christian Medical College, Vellore in teaching behavioural sciences. Students are taught sociology, psychology and medical anthropology through a community-based, problem-oriented teaching programme. The students have first-hand experience of living in a community and learn by observation and interaction. Pre- and post-assessment has shown a significant improvement of their knowledge and attitude. Feedback from students also indicates that they find this programme relevant and interesting.

Behavioral Sciences↗

PubMed1992

Oral clonidine pretreatment for haemodynamic stability during craniotomy.

We have studied the effect of clonidine pretreatment on cardiovascular responses to various stimuli during craniotomy. Fifty-eight patients (ASA Class I-II), scheduled for supratentorial surgery, were randomly given either oral clonidine, mean dose 3.6 micrograms/kg (n = 28), or oral diazepam, 0.2 mg/kg (n = 30), ninety to one hundred minutes before surgery. Anaesthesia was induced with thiopentone and maintained with nitrous oxide:oxygen, pentazocine and halothane. Pancuronium was used as a neuromuscular blocker. Mean arterial pressure and heart rate were recorded before and after several stimuli. In the clonidine group hypertensive response was significantly less on laryngoscopy (6.5% increases versus 11.2% in the diazepam group), intubation (9.2% versus 16.5%), Mayfield clamp application (14.5% versus 29.91%) and after skin infiltration with lignocaine-adrenaline solution (2.95% versus 5.42%). Heart rate response to laryngoscopy, intubation and skin infiltration was also significantly attenuated in the clonidine group. The sleep dose of thiopentone was smaller in patients pretreated with clonidine. Patients in the diazepam group required more medical intervention. No adverse effect occurred in any patient.

Administration, Oral↗

PubMed1992

Characterization of the percepts evoked by discontinuous motion over the perioral skin.

The capacity of human subjects to process information about discontinuous and continuous movement was evaluated. Constant-velocity brushing stimuli were delivered through aperture plates that rested lightly upon the mandibular skin. Each plate consisted of either two spatially separated, slit-like openings or a single continuous, longer opening. It was discovered that percepts of smooth apparent motion were achieved with the split apertures (i.e., from discontinuous movement) for only limited ranges of stimulus velocity. Moreover, the optimal velocity supporting smooth apparent motion increased with the separation between the slit-like openings. In a second series of experiments, subjects' ability to discriminate opposing directions of discontinuous and continuous movement was evaluated. It was found that subjects could derive directional information from percepts elicited by discontinuous movement. However, the capacity to discriminate opposing directions of continuous movement cannot be explained solely in terms of the ability to process information about the change in position of a stimulus from its onset to its offset.

Discrimination Learning↗

PubMed1992

Scatter factor and hepatocyte growth factor: activities, properties, and mechanism.

Scatter factor (SF) was first identified as a fibroblast-derived protein which disperses (i.e., "scatters") cohesive colonies of epithelium. SF-like proteins were found in human smooth muscle cell conditioned medium, amniotic fluid, and placental tissue. SFs markedly stimulate migration of epithelial, carcinoma, and vascular endothelial cell types at picomolar concentrations. Hepatocyte growth factors (HGFs) were originally described as platelet- and serum-derived proteins which stimulate hepatocyte DNA synthesis. Partial amino acid sequence data for mouse and human SFs indicate significant homology with HGFs. We used biological, biochemical, and immunological assays to evaluate and compare the activities, properties, and mechanisms of action of mouse SF, human SF (fibroblast or placenta derived), and recombinant human HGF (hrHGF). We report the following findings: (a) mouse SF exhibits species-related differences in biological activities relative to the human factors; (b) human SF and hrHGF show significant overlap in biological activities (i.e., hrHGF stimulates motility of multiple normal and carcinoma cell types, whereas human SF stimulates DNA synthesis in several normal cell types); (c) the three factors contain common antigenic determinants; and (d) all three proteins stimulate rapid phosphorylation of tyrosine residues on the c-met protooncogene protein product (the putative receptor for HGF) and on another protein with Mr 110,000. A few biological and immunological differences between human SFs and hrHGF were observed. These may reflect minor variations in amino acid sequence or posttranslational modification related to the sources of the factors. Taken as a whole, our findings suggest that by structural, functional, immunological, and mechanistic criteria, human SF and human HGF are essentially identical.

Amino Acid Sequence↗

PubMed1991

Preliminary experience with 5 and 6 French diagnostic catheters as guiding catheters for coronary angioplasty.

With the reduction in profile of balloon dilation catheters, until recently, it has been the internal dimensions and performance of the guiding catheter that has mandated the use of 7, 8 or 9 French (F) systems for the performance of percutaneous transluminal coronary angioplasty (PTCA). A new 5F catheter design (Sherwood Medical Co., St. Louis, MO) provided a large inner lumen (0.4") permitting use of 0.20-0.22" fixed-wire PTCA balloon catheters with good coronary visualization. Potential advantages include reduced coronary artery ostial trauma and catheter induced damping and enhanced patient comfort. We report our initial experience in 14 patients undergoing PTCA with a 5 and 6F guide/fixed-wire system. Mean age was 63 +/- 10 (43-78 years). PTCA indications: Cardiogenic shock (1), post-myocardial infarction angina pectoris (2), grade III angina (5) and unstable angina pectoris (6). Vessel attempted: Left anterior descending (3), circumflex (4), obtuse marginal (2), diagonal (1), right coronary artery (3), and internal thoracic artery (1). Twelve patients had femoral approach; two brachial approach. The USCI Probe (USCI Division, Billerica, MA) was used in 8 lesions and SCIMED ACE (SCIMED Life Systems, Maplegrove, MN) catheter in 7 lesions. Successful 5 or 6F guide/fixed-wire dilations reduced the stenosis (77 +/- 14 to 37 +/- 30%) and were successfully performed in 79% (11/14). One 5F patient required 8F guiding catheter and was dilated with 2.0 fixed-wire balloon. A second failed 5F PTCA could not be dilated with any larger conventional system. A third total occlusion could not be crossed with a guidewire or fixed wire balloon. No patient had a complication.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

PubMed1991

Multicenter evaluation of a new fixed-wire coronary angioplasty catheter system: clinical and angiographic characteristics and results.

Coronary angioplasty is increasingly used as an attempt to revascularize patients with severe coronary artery disease. To determine the efficacy of such treatment, a new fixed wire angioplasty catheter was evaluated by a multicenter group in a non-randomized fashion in 50 patients, average 58 +/- 11 years (+/- 1 SD), 58% men. Forty-four percent had a prior revascularization procedure (28% angioplasty, 16% coronary bypass surgery), 38% had a prior Q-wave myocardial infarction, 43% had grade 4 angina, and 60% multiple vessel disease. Angioplasty was attempted in 63 lesions which were located in a mid to distal location in 69%, with a proximal tortuosity score of 1.8 (2 = 45-60 degrees entrance angle), and lesion angulation of 1.4 (1 = 45 degrees lesion bend). In 88%, the device was the primary catheter used and in 6%, it was chosen when another system failed. The balloon was able to successfully cross 94% of all lesions attempted. Six lesions were crossed and dilated but significant residual stenoses remained. There were no significant device malfunctions, or angiographic or clinical complications. This feasibility evaluation of this new fixed wire system yielded excellent angiographic results. Although not a comparative study, this analysis suggests that this new generation of angioplasty catheter may improve the safety and efficacy of complex coronary angioplasty.

Angiography↗

PubMed1991

Purification, characterization and mechanism of action of scatter factor from human placenta.

Scatter factor (SF) causes contiguous sheets of epithelium to spread and cells to separate from each other. SF also increases the velocity, area, and reduces the circularity of individual cells. These changes are mediated in part by alterations in protein synthesis, protein phosphorylation, cytoskeletal reorganization, and cell surface components. SF has been purified from the conditioned medium of ras transformed 3T3 cells and human placenta. Sequence information suggests that SF from 3T3 cells is closely related to hepatocyte growth factor. SF is a glycoprotein, but glycosylation is not necessary for its activity. Glycosylation of target cell proteins, however, is required for SF action.

Animals↗

PubMed1991

Excimer laser-assisted femoral angioplasty: early results.

The ability to ablate atheroma without generating heat makes the excimer laser wavelength a promising intraluminal technique for the treatment of arterial occlusive disease. This series reviews a preliminary experience treating patients with superficial femoral arterial disease admitted with limb-threatening ischemia or claudication. Twenty-six diseased superficial femoral arteries (5 stenotic and 21 occluded) were treated in 23 consecutive patients. Patients with claudication (18) reluctant to undergo bypass or with limb-threatening ischemia (8) at extremely high risk for surgery were included. There were 10 men and 13 women with a mean age of 67 years. A 308 nm excimer laser with an over-the-wire catheter (19) or balloon-centered end-on catheter (7) was used followed by balloon angioplasty. Twenty-four procedures were performed percutaneously, and two were performed with the vessel open in the operating room. Technical success, defined as disobliteration confirmed by angiography and greater than 0.15 increase of the ankle/brachial index, was achieved in 15 of 26. Eleven of 21 occlusions (52%) and four of five stenoses (80%) were opened. Only two of 11 lesions longer than 10 cm were successfully treated. Unsuccessful attempts (technical failure) occurred in 11 of 26 patients and resulted in four elective and one emergency femoral-popliteal bypass. Five patients were discharged with their claudication unchanged, and one had an elective amputation. Six arterial perforations with three arteriovenous fistulas occurred, all resolved without operation. No unanticipated limb loss occurred. In the 15 successful cases, the mean ankle/brachial index increase was 0.34. Seven (47%) of these 15 remain patent with a mean follow-up of 9.5 months (1.5 to 14 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

An insular outbreak of dengue fever in a rural south Indian village.

In mid 1990, an epidemic of fever affected a single village in Kaniyambadi Block, South India. The illness was characterized by a fever of approximately five days duration, accompanied by headache, chills, sweating and muscle pain. The overall attack rate was 22.5 per cent. The attack rate was uniform across the various age groups and between the sexes. Testing of the acute and convalescent serum samples obtained from cases showed a serological response to dengue virus. The Aedes house index in the village was found to be 36 per cent with toilets serving as active breeding sites. Adjacent villages studied showed similarly high rates of Aedes prevalence, although no cases of the same fever were seen. Since previous exposure to dengue increases the risk for epidemics of dengue hemorrhagic fever and dengue shock syndrome, health education on methods of Aedes control is continuing.

Adolescent↗

PubMed1991

[Immunoscintigraphy using 111Indium-labeled antimyosin in suspected myocarditis].

111Indium-monoclonal antimyosin scans were carried out in 21 patients with suspected myocarditis, confirmed by reduced ejection volume, pericardial effusion and clinical follow up in 12 patients. Coronary heart disease was excluded angiographically in all cases. Quantitative evaluation of myocardial 111In-antimyosin accumulation 48 hours after injection showed a pathological uptake in 10/12 patients with increased heart/lung ratios (Q48 greater than 1.58). Ratios were also elevated in 2 patients with cardiomyopathy, 2 suffering from vasculitis and 1 with dermatomyositis. Four patients without proven cardiac disease had normal ratios (Q48 less than or equal to 1.58). Examination after 24 hours was of limited value, depending on the residual blood pool activity. Visual analysis of the scans showed a high interobserver variation despite a positive correlation with quantitative analysis (48 h p.i.: r = 0.72; p less than 0.001), and is not recommended. The results show the value of the 111In-antimyosin scan as a screening method prior to myocardial biopsy. However, scintigraphy cannot definitely elucidate the cause of myocardial damage. Therefore, myocardial biopsy is still recommended after positive antimyosin scans.

Adolescent↗

PubMed1990

Preliminary results utilizing a new percutaneous transluminal coronary angioplasty balloon catheter.

We report our initial experience with a new percutaneous transluminal coronary angioplasty (PTCA) balloon catheter and compare it to a similar over-the-wire system in a retrospective, nonrandomized fashion. There was no statistical difference in pre-PTCA angiographic indices and post-PTCA angiographic and clinical success rates between the two groups. There was a trend toward a decrease in length of fluoroscopy (P = .08) and a significant decrease in the amount of contrast utilized (P = .007) with the new balloon catheter. Several new construction features of the new catheter account for this improvement and are discussed. The long-term success of this balloon catheter remains to be investigated.

Adult↗

PubMed1990

Acute myocardial infarction delineated by noninvasive thallium-201/technetium-99m pyrophosphate tomography.

The purpose of this study was to validate different scintigraphic approaches for assessing acute myocardial infarctions. 201Tl, 99Tcm pyrophosphate (PPi) and combined 201Tl/99Tcm PPi tomograms were evaluated in 115 consecutive patients, in 85 of whom clinical examination revealed acute myocardial infarction. The overall sensitivity and specificity for infarct detection was 80% versus 56% for 201Tl alone, 61% versus 97% for 99Tcm PPi alone, and 100% each for the combined 201Tl/99Tcm PPi imaging. The sensitivity for nontransmural infarcts was 57% for 201Tl, 37% for 99Tcm PPi and 100% for combined imaging. The overlay of 201Tl and 99Tcm PPi images increases the observer's confidence in the diagnosis and provides better localization of the infarction. 201Tl alone could localize the infarction in 80%, 99Tcm PPi alone in 49% and 201Tl/99Tcm PPi in 100% of the cases. ECG and 201Tl/99Tcm PPi tomography concurred upon infarct localization in 98% of the patients. Based on the 201Tl/99Tcm accumulation pattern, 94% of the Q-wave infarctions were judged to be transmural and 83% of the non-Q-wave infarctions were judged to be nontransmural. It is concluded that combined 201Tl/99Tcm PPi tomography is highly accurate for determining the presence and location of acute myocardial infarction. This technique appears to be superior to studies where only one radioisotope is used.

Adult↗

PubMed1990

Teaching nutrition to medical students: a community-based problem-solving approach.

This paper presents a community-based problem-solving educational programme which aims at teaching medical and other health science students the importance of nutrition and its application. Through community surveys students assess the nutritional status of children under five using different anthropometric methods. They understand the cultural beliefs and customs related to food fads and the reasons for them. They also acquire the skill to educate the community using the information gathered. They use epidemiological methods such as case control study to find associations between malnutrition and other causative factors. Feedback from students has been positive and evaluation of students' knowledge before and after the programme has shown significant improvement.

Community Medicine↗