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Biomedical subjects

R Mody

Publications and source records attributed to R Mody.

14 recordsLinked to original sources
PubMed2001

Localization of a human reduced folate carrier protein in the mitochondrial as well as the cell membrane of leukemia cells.

IgG polyclonal antiserum was generated in New Zealand White rabbits immunized with a 16-mer peptide consisting of a specific amino acid sequence at residues corresponding to the sixth to seventh predicted transmembrane domain of the human reduced folate carrier (RFC). Using Western immunoblotting to examine the cytosolic and membrane fractions of the human CCRF-CEM T-cell lymphoblastic leukemia cell line, polyclonal antihuman RFC antiserum recognized two bands in the cytosolic fraction (approximately 60 kDa and approximately 70 kDa) on 10% polyacrylamide gels. In the membrane fraction, an approximately 60-kDa protein was identified. Comparative studies of a panel of human tumor cell lines including the HT1080 fibrosarcoma, 8805 malignant fibrous histiocytoma, and the MCF breast cancer cell lines revealed similar findings. Likewise, a recombinant approximately 60-kDa membrane protein was identified after expression of baculovirus-infected Sf9 insect cells containing cDNA of the human RFC. In the CEM-7A cell line, a variant of the CCRF-CEM cell line that overexpresses the RFC, 21-fold overexpression of the approximately 60-kDa membrane protein (RFC) was shown by Western analysis. To characterize further the cellular distribution of the human RFC, immunohistochemical analyses were performed in CCRF-CEM T-cell lymphoblastic leukemia cells. Predominantly membrane localization of the antibody reacting sites was detected; however, a cytoplasmic component was noted as well. By confocal microscopy and by immunogold electron microscopy, the cytoplasmic expression was found to be largely of mitochondrial origin. These findings were corroborated by Western immunoblotting of mitochondrial membrane isolates from the CCRF-CEM cell line, which demonstrate an approximately 60-kDa protein. The localization of the human RFC to the mitochondrial membrane is a novel finding, and it suggests a role for the mitochondrial membrane in the transport of folates.

Animals↗
PubMed1995

Use of lectins as diagnostic and therapeutic tools for cancer.

Within the past few years, lectins have become a well-established means for understanding varied aspects of cancer and metastasis. Evidence is now emerging that lectins are dynamic contributors to tumor cell recognition (surface markers), cell adhesion and localization, signal transduction across membranes, mitogenic stimulation, augmentation of host immune defense, cytotoxicity, and apoptosis. To advance understanding of these lectin-dependent processes, attempts are being made to discover new lectins that have one or more of these functions and to develop lectin- (or glycoconjugate-) based tools that could be used to home in on tumor cells. This review will summarize current research on the lectins and recent advances in the development of lectin-based diagnostic and therapeutic tools for cancer. Additionally, the future potential of lectin-based diagnosis and therapy is discussed.

Animals↗
PubMed1994

Spontaneous hydrolysis of vasoactive intestinal peptide in neutral aqueous solution.

Hydrolysis of radioiodinated vasoactive intestinal peptide (VIP) was observed in buffered aqueous solution at neutral pH and 38 degrees C. The reaction displayed apparent first-order kinetics at initial peptide concentrations below 3 nM (kobs = 1.5 x 10(-5) s-1), but the rate deviated below predicted values at higher peptide concentrations. The rate constant derived from the reaction progress curve over three half lives, starting at a concentration of 82 pM peptide, was also consistent with a first-order process. The reaction results in several products that were isolated and characterized as peptide fragments. Based on the identity of these fragments, we deduced hydrolysis at five different peptide bonds clustered between residues 17-25 of VIP. Control experiments were devised to eliminate trivial explanations for the peptide hydrolysis. Peptides representing the C-terminal segment 15-28 and the internal segment 14-22 assayed by analogous methods and under identical conditions were not degraded at a measurable rate. Sodium dodecyl sulfate and acetonitrile, agents known to influence the secondary structure of VIP, inhibited its spontaneous hydrolysis, as did chloride salts of sodium and calcium, albumin and a peptide unrelated to VIP. The rate and product distribution are inconsistent with known pathways of peptide degradation involving cyclic imide or anhydride formation at asparagine or aspartate residues. We suggest that the breakdown of VIP in dilute solutions represents an autolytic process.

Amino Acid Sequence↗
PubMed1992

Peptidolytic monoclonal antibody elicited by a neuropeptide.

We report evidence that a monoclonal antibody raised by immunization with a vasoactive intestinal peptide (VIP)-carrier protein conjugate selectively hydrolyzes VIP and a fluorescence quenched decapeptide (FQ14-22D), representing the region of VIP most susceptible to autoantibody-mediated cleavage (residues 14-22). A high affinity of the antibody for VIP and a lower affinity for FQ14-22D were revealed by kinetic studies and further substantiated by potent inhibition of FQ14-22D cleaving activity by full-length VIP. Sequencing of FQ14-22D hydrolysis products indicated selective cleavage at one peptide bond. These observations suggest that antibodies induced against naturally occurring polypeptide antigens can express peptidolytic activity targeted for specific sequences in the recognition epitope.

Amino Acid Sequence↗
PubMed1991

Damage to the plasma membrane in Escherichia coli K-12 induced by far-ultraviolet radiation and its repair.

Escherichia coli cells treated with low fluences of far-uv radiation (up to 90 J/m2) showed repairable damage to the plasma membrane. The loss of the ability of the cells to exclude citrate was evident from the respiratory stimulation of irradiated cells when citrate was provided exogenously. This loss of a barrier was a result of a structural disorganization of the plasma membrane as seen by freeze-etching electron microscopy. Analysis of the plasma membrane proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed a characteristic loss of certain membrane proteins. When irradiated cells were incubated in glucose minimal medium at 37 degrees C for various times, a gradual recovery of membrane structure and function was observed. The recovery process was inhibited in the absence of an energy source as well as protein synthesis. The majority of the recovery occurred in the initial 1 h of the postirradiation holding. These results demonstrated that far-uv radiation at a fluence less than the D10 value had a direct or indirect effect on plasma membrane proteins, causing their release from the membrane bilayer. The lost proteins were subsequently regained by de novo protein synthesis.

Cell Membrane↗
PubMed1989

Influence of far-ultraviolet radiation on the permeability of the outer membrane of Escherichia coli.

Far-ultraviolet radiation (254 nm) at a dose of 10, 20, and 30 J/m2 was found to disrupt the outer membrane permeability barrier of Escherichia coli to various antibiotics, dyes, and detergents. The degree of sensitization to these agents was proportional to the radiation dose. The irradiated cells showed a significant increase in the sensitivity of hydrophilic antibiotics (ampicillin, carbenicillin, penicillin), whereas much less sensitization was found towards hydrophobic probes (kanamycin, erythromycin, rifamycin SV, crystal violet, phenol, novobiocin) and detergents (dodecyl sulfate, bile salt, Triton X-100). The biochemical data and ultrastructural analysis of the outer membrane by freeze-etching have shown that the increase in phospholipid:protein ratio after irradiation had changed the architecture of the outer membrane from a highly asymmetric bilayer structure with densely packed lipopolysaccharide--protein particles on the outer half, to one predominantly exhibiting smooth phospholipid bilayer characteristics. The structure, composition, and barrier function of the outer membrane were restored to normal within 3 h of postirradiation incubation in nonproliferative medium. During this period, the acquisition of resistance towards a hydrophilic antibiotic (ampicillin) was faster than that for a hydrophobic agent (phenol).

Anti-Bacterial Agents↗
PubMed1987

Does sodium play an adverse role in hypertension?

It is clear that salt is known to be a health hazard from the ancient times. Sodium intake, which was minimal during evolution, increased significantly with the civilization. The rise in prevalence of hypertension in populations with increased consumption of salt suggested a casual relationship. However, several of these studies showed conflicting results. Many investigators agree that salt-sensitive persons often have a family history of hypertension. Such individuals possess a sodium transport inhibitor in the arterial smooth muscle cells, which affects their sodium handling (as compared to other persons). However, many of the putative defects related to sodium can be dissociated from blood pressure and sodium consumption status. It is possible that calcium defects of deficiency of potassium and magnesium follow hypertension and sodium status. For example, the pressure response to sodium chloride may be dissociated from sodium, which may be secondary to adverse effects of chloride on calcium homeostasis. Clinical studies also indicate that the role of sodium is controversial in hypertension. Sodium restriction can benefit salt-sensitive persons and might not otherwise. However, most authorities believe that moderation of salt intake to a relevant extent is justifiable. Large scale, long-term intervention studies and shortterm clinical studies in different communities, in the light of recently investigated dietary factors, are necessary to establish the role of sodium in essential hypertension.

Animals↗
PubMedDate not supplied

Effect of diet and weight reduction in hypertension.

Weight reduction by a low-energy diet and a high-polyunsaturates-, fiber- and potassium-rich diet may be independently useful to hypertensives. To study the effect of such diets, 416 hypertensives were randomized to either a low-energy cardiovasoprotective (CVP) diet (Group A; n = 106), a low-energy usual diet (Group B; n = 104), an optimal-energy CVP diet (Group C; n = 104), or an optimal-energy, usual pre-experimental diet (Group D; n = 102) plus drug therapy in a single-blind and controlled fashion. Groups A and B received significant (p less than 0.02) fewer calories per day than Groups C and D. Groups A and C also received significantly (p less than 0.02) more calories per amount of complex carbohydrates, polyunsaturates, potassium, and magnesium than did Groups B and D. Dietary compliance and drug intake was checked weekly. After 3 months, there was a significant fall in mean serum cholesterol (p less than 0.01) and mean serum triglycerides (p less than 0.05) in Group A compared with Group D. Group A and B patients had a loss of around 10kg of mean body weight, with no weight change seen in Group D. Weight loss was associated with a significant fall in systolic and diastolic pressures in both Group A (22/18mmHg) and Group B (16/13mmHg) compared with Group D at the end of the study. Group C patients also showed a significant fall in pressure (13/10mmHg) compared with Group D. Drug therapy, exercise, and salt intake were similar in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗