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Biomedical subjects

R Kumar

Publications and source records attributed to R Kumar.

At least 271 records · Page 15Linked to original sources
PubMed2000

Generalized thermoelastic waves in homogeneous isotropic plates

The propagation of thermoelastic waves in homogeneous isotropic plate subjected to stress-free and rigid insulated and isothermal conditions is investigated in the context of conventional coupled thermoelasticity (CT), Lord-Shulman (LS), Green-Lindsay (GL), and Green-Nagdhi (GN) theories of thermoelasticity. Secular equations for the plate in closed form and isolated mathematical conditions for symmetric and skew-symmetric wave mode propagation in completely separate terms are derived. It is shown that the motion for SH modes gets decoupled from the rest of the motion and remains unaffected due to thermo-mechanical coupling and thermal relaxation effects. The phase velocities for SH modes have also been obtained. The results for coupled and uncoupled theories of thermoelasticity have been obtained as particular cases from the derived secular equations. At short wavelength limits the secular equations for symmetric and skew-symmetric waves in a stress-free insulated and isothermal plate reduce to Rayleigh surface waves frequency equations. Finally, the numerical solution is carried out for aluminum-epoxy composite material and the dispersion curves for symmetric and skew-symmetric wave modes are presented to illustrate and compare the theoretical results.

Journal Article↗
PubMed2000

Evidence of Rab3A expression, regulation of vesicle trafficking, and cellular secretion in response to heregulin in mammary epithelial cells.

Heregulin beta1 (HRG), a combinatorial ligand for human growth factor receptors 3 and 4, is a regulatory polypeptide that promotes the differentiation of mammary epithelial cells into secretory lobuloalveoli. Emerging evidence suggests that the processes of secretory pathways, such as biogenesis and trafficking of vesicles in neurons and adipose cells, are regulated by the Rab family of low-molecular-weight GTPases. In this study, we identified Rab3A as a gene product induced by HRG. Full-length Rab3A was cloned from a mammary gland cDNA library. We demonstrated that HRG stimulation of human breast cancer cells and normal breast epithelial cells induces the expression of Rab3A protein and mRNA in a cycloheximide-independent manner. HRG-mediated induction of Rab3A expression was blocked by an inhibitor of phosphatidylinositol 3-kinase but not by inhibitors of mitogen-activated protein kinases p38(MAPK) and p42/44(MAPK). Human breast epithelial cells also express other components of regulated vesicular traffic, such as rabphilin 3A, Doc2, and syntaxin. Rab3A was predominantly localized in the cytosol, and HRG stimulation of the epithelial cells also raised the level of membrane-bound Rab3A. HRG treatment induced a profound alteration in the cell morphology in which cells displayed neuron-like membrane extensions that contained Rab3A-coated, vesicle-like structures. In addition, HRG also promoted the secretion of cellular proteins from the mammary epithelial cells. The ability of HRG to modify exocytosis was verified by using a growth hormone transient-transfection system. Analysis of mouse mammary gland development revealed the expression of Rab3A in mammary epithelial cells. Furthermore, expression of the HRG transgene in Harderian tumors in mice also enhanced the expression of Rab3A. These observations provide new evidence of the existence of a Rab3A pathway in mammary epithelial cells and suggest that it may play a role in vesicle trafficking and secretion of proteins from epithelial cells in response to stimulation by the HRG expressed within the mammary mesenchyma.

Animals↗
PubMed2000

Reduced synthesis of muscle proteins in chronic renal failure.

Muscle wasting and weakness occur frequently in patients with chronic renal failure. The mechanism(s) by which these abnormalities occur is unclear. We hypothesized that such findings were due to defective muscle protein synthesis. We measured synthetic rates of mixed muscle proteins, myosin heavy chain, and mitochondrial proteins in serial muscle biopsy samples during a continuous infusion of L[1-(13)C]leucine from 12 patients with chronic renal failure and 10 healthy control subjects under identical study conditions. Patients with chronic renal failure have significantly lower synthetic rates of mixed muscle proteins and myosin heavy chain (27 and 37% reductions, respectively, P < 0.05 and P < 0.02). Significant declines in the synthetic rates of muscle mitochondrial protein (27%) (P < 0.05), muscle cytochrome c-oxidase activity (42%) (P < 0.007), and citrate synthase (27%) (P < 0.007) were also observed in patients with chronic renal failure. The synthetic rates of muscle proteins and activity of mitochondrial enzymes were negatively correlated to the severity of renal failure. These results indicate that in chronic renal failure there is a decrease in the synthesis of muscle contractile and mitochondrial proteins and a decrease in muscle mitochondrial oxidative enzymes. Reduced synthetic rate of several muscle proteins is the likely biochemical basis of muscle loss and muscle weakness in people with chronic renal failure.

Adult↗
PubMed2000

Measurements of calcium transients in ventricular cells during discontinuous action potential conduction.

The L-type calcium current (I(Ca)) is important in sustaining propagation during discontinuous conduction. In addition, I(Ca) is altered during discontinuous conduction, which may result in changes in the intracellular calcium transient. To study this, we have combined the ability to monitor intracellular calcium concentration ([Ca(2+)](i)) in an isolated cardiac cell using confocal scanning laser fluorescence microscopy with our "coupling clamp" technique, which allows action potential propagation from the real cell to a real-time simulation of a model cell. Coupling a real cell to a model cell with a value of coupling conductance (G(C) = 8 nS) just above the critical value for action potential propagation results in both an increased amplitude and an increased rate of rise of the calcium transient. Similar but smaller changes in the calcium transient are caused by increasing G(C) to 20 nS. The increase of [Ca(2+)](i) by discontinuous conduction is less than the increase of I(Ca), which may indicate that much of [Ca(2+)](i) is the result of calcium released from the sarcoplasmic reticulum rather than the integration of I(Ca).

Action Potentials↗
PubMed2000

Electrical interactions between a real ventricular cell and an anisotropic two-dimensional sheet of model cells.

We have extended our "coupling clamp" technique, in which we couple a real cell to a real-time simulation of a model cell, to now incorporate a real cardiac cell as the central element of a two-dimensional sheet of model cells, in which the coupling conductances may be different in the x and y directions and a specific region of lack of coupling conductance may serve as a resistive barrier. We stimulated the real cell in the central location and determined the critical size of the real cell for successful activation of the entire sheet. We found that this critical size was decreased when anisotropy was present compared with the isotropic case and was further decreased when the central site of stimulation was close to the resistive barrier. The heart normally has some degree of anisotropy, and it has been shown that the remodeling that occurs in peri-infarction zones produces a particular loss of lateral connections compared with end-to-end connections among heart cells. We propose that the normal existence of anisotropy and enhancement of the degree of anisotropy both by loss of lateral gap junctions and the development of resistive barriers may play a facilitating role in the development of ectopic foci that may lead to cardiac arrhythmias.

Animals↗
PubMed2000

A spontaneously active focus drives a model atrial sheet more easily than a model ventricular sheet.

Tachycardias can be produced when focal activity at ectopic locations in either the atria or the ventricles propagates into the surrounding quiescent myocardium. Isolated rabbit atrioventricular nodal cells were coupled by an electronic circuit to a real-time simulation of an array of cell models. We investigated the critical size of an automatic focus for the activation of two-dimensional arrays made up of either ventricular or atrial model cells. Over a range of coupling conductances for the arrays, the critical size of the focus cell group for successful propagation was smaller for activation of an atrial versus a ventricular array. Failure of activation of the arrays at smaller focus sizes was due to the inhibition of pacing of the nodal cells. At low levels of coupling conductance, the ventricular arrays required larger sizes of the focus due to failure of propagation even when the focus was spontaneously active. The major differences between activation of the atrial and ventricular arrays is due to the higher membrane resistance (lower inward rectifier current) of the atrial cells.

Animals↗
PubMed2000

Fast pacing facilitates discontinuous action potential propagation between rabbit atrial cells.

We examined the critical coupling conductance (G(C)) for propagation at different pacing cycle lengths (CLs) (1,000 and 400 ms). As G(C) was progressively reduced, propagation failed at a CL of 1,000 ms, whereas propagation succeeded at a CL of 400 ms over a range of G(C) values before failing at a CL of 400 ms at a lower G(C), showing facilitation of propagation at the shorter CL. Critical G(C) was (means +/- SE) 0.8 +/- 0.1 nS for a CL of 400 ms and 1.3 +/- 0.1 nS for a CL of 1,000 ms (a 63% increase, P < 0.002, n = 9 cell pairs). In 14 uncoupled cells, action potential duration at 30% repolarization (APD(30)) increased from 19.9 +/- 2.5 to 41.8 +/- 2.6 ms (P < 0.001) as CL decreased from 1,000 to 400 ms. In five cell pairs, critical G(C) with 4-aminopyridine (4-AP) was reduced to 0.4 +/- 0.1 nS at a CL of 1,000 ms (P < 0.05 compared with control solution), and critical G(C) in 4-AP was unchanged by decreasing CL to 400 ms. It is possible that the "remodeling" of atrial cells due to atrial fibrillation or tachycardia, which has been shown to produce a decrease in the transient outward current, may result in an enhanced ability to propagate, possibly facilitating further development of fibrillation under conditions of decreased cellular coupling.

Action Potentials↗
PubMed2000

Value of barium swallow in investigation of globus pharyngeus.

Globus pharyngeus as a possible presenting symptom of a pharyngeal or upper oesophageal neoplasm is the main reason why barium swallows are requested, although it is essentially a benign disorder that in many cases requires reassurance only. We therefore retrospectively reviewed all barium swallows done in our department for globus pharyngeus during a one-year period to assess their value in the investigation of this condition. Ninety-two patients were identified. All had a normal ENT examination, and symptoms suggestive of acid reflux was the most common associated complaint, at 11 per cent. Acid reflux (18.5 per cent) and hiatus hernia (12 per cent) were the commonest findings of a barium swallow. Three cases of suspicious findings on barium swallow had a normal examination under general anaesthetic. Statistical analysis showed no significant relationship between the symptoms of globus and the barium swallow results. A barium swallow does not seem to add any further useful information to the investigation of globus pharyngeus. But most globus patients will continue to undergo a barium swallow, because although alternative investigations have been extensively assessed, it is still not clear which is the most appropriate mode of investigation for this condition.

Adolescent↗
PubMed2000

Parathyroid hormone regulates transforming growth factor beta1 and beta2 synthesis in osteoblasts via divergent signaling pathways.

Parathyroid hormone 1-34 [PTH(1-34)] was shown to increase transforming growth factor beta1 (TGF-beta1) and TGF-beta2 concentrations in supernatants of cultured human osteoblasts and to increase TGF-beta1 and TGF-beta2 messenger RNA (mRNA) concentrations and gene transcription in these cells. Because PTH(1-34) activates both protein kinase C (PKC) and protein kinase A (PKA) pathways in osteoblasts, we investigated the role of each kinase pathway in activation of TGF-beta isoforms. PTH(29-32), which activates the PKC pathway in rat osteoblasts, increased TGF-beta1 but not TGF-beta2 concentrations in supernatants of osteoblasts. Phorbol myristate acetate (PMA), a PKC agonist, increased TGF-beta1 but not TGF-beta2 concentrations. Specific PKC antagonists safingol and Gö6976 attenuated PTH(1-34)-mediated increases in TGF-beta1 but not TGF-beta2 synthesis. PTH(1-31), which increases PKA activity in several cell culture systems, increased TGF-beta2 but not TGF-beta1 concentrations in human osteoblast supernatants. Forskolin, a PKA agonist, increased TGF-beta2 but not TGF-beta1 concentrations in supernatants of human osteoblasts. The PKA antagonist H-89 blunted PTH(1-34)-mediated increases in TGF-beta2 but not TGF-beta1 synthesis. Our results are consistent with the concept that PTH increases TGF-beta1 expression and secretion by pathways that involve the PKC pathway, whereas it increases TGF-beta2 expression and secretion via the PKA pathway.

Animals↗
PubMed2000

Apoptosis in mammary gland and cancer.

Homeostasis in normal tissue is regulated by a balance between proliferative activity and cell loss by apoptosis. Apoptosis is a physiological mechanism of cell loss that depends on both pre-existing proteins and de novo protein synthesis, and the process of apoptosis is integral to normal mammary gland development and in many diseases, including breast cancer. The mammary gland is one of the few organ systems in mammals that completes its morphologic development postnatally during two discrete physiologic states, puberty and pregnancy. The susceptibility of the mammary gland to tumorigenesis is influenced by its normal development, particularly during stages of puberty and pregnancy that are characterized by marked alterations in breast cell proliferation and differentiation. Numerous epidemiologic studies have suggested that specific details in the development of the mammary gland play a critical role in breast cancer risk. Mammary gland development is characterized by dynamic changes in the expression profiles of Bcl-2 family members. The expression of Bcl-2 family proteins in breast cancer is also influenced by estradiol and by progestin. Since the ratio of proapoptotic to antiapoptotic proteins determines apoptosis or cell survival, hormone levels may have important implications in the therapeutic prevention of breast cancer.

Animals↗
PubMed2000

A prospective randomized study of Chop versus Chop plus alpha-2B interferon in patients with intermediate and high grade non-Hodgkin's lymphoma: the International Oncology Study Group NHL1 Study .

UNLABELLED: The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. BACKGROUND: The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin's lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. PATIENTS AND METHODS: Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. RESULTS: The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. CONCLUSIONS: There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Functional domains and expression of truncated atrial natriuretic peptide receptor-A: the carboxyl-terminal regions direct the receptor internalization and sequestration in COS-7 cells.

The objective of this study was to determine the role of cytoplasmic (protein kinase-like homology and guanylyl cyclase catalytic) domains of atrial natriuretic peptide (ANP) receptor-A (Npra) in postbinding events and metabolic turnover of ligand-receptor complexes. Using deletion mutagenesis, the specific regions in the intracellular domains of Npra relevant to the receptor function, namely ligand-binding, cGMP production, and internalization and sequestration of ligand-receptor complexes, have been determined in transiently expressing COS-7 cells. Deletion of 12 aa (aa) at the carboxyl-terminal end of receptor (Delta1045-Npra) affected neither ligand-binding efficiency nor cGMP production. However, deletion of 120 to 170 aa residues (Delta937-Npra, Delta916-Npra, Delta902-Npra, and Delta887-Npra) decreased ligand binding by 16 to 20% and cGMP production by 50 to 90%. Further deletion of 422 aa and 569 aa (Delta635-Npra and Delta488-Npra) reduced ligand binding efficiency by 40% and 90%, respectively. The deletion of 12 aa (Delta1045-Npra) did not affect the internalization of Npra; however, deletions up to 170 aa (Delta937-Npra, Delta916-Npra, Delta887-Npra) reduced the internalization of ligand-receptor complexes by 60%. Cells expressing either full-length (wild-type) Npra or 120 aa deleted receptor (Delta937-Npra) released 40 to 45% (125)I-ANP radioactivity into culture medium, but only 10 to 15% radioactivity was released from the cells that expressed Delta635-Npra. Furthermore, 35 to 40% (125)I-ANP radioactivity was detected into the intracellular compartments of cells that expressed the wild-type Npra, and only 5 to 10% (125)I-ANP radioactivity was observed in cells expressing the Delta635-Npra (-422 aa) or Delta488-Npra (-569 aa) mutant receptors. These results show that specific regions within the intracellular domains of Npra determine the extent of ligand-binding efficiency, cGMP production, endocytosis, and intracellular sequestration of ligand-receptor complexes in cDNA expressing COS-7 cells.

Animals↗
PubMed2000

Retrocerebellar arachnoid cyst with syringomyelia: a case report.

Association of syringomyelia with retrocerebellar arachnoid cysts is rare. A case of 14 year old female is being reported, who presented with hydrocephalus caused by a large midline retrocerebellar infravermal arachnoid cyst leading to obstruction of the outlet foramina of the fourth ventricle. There was associated syringomyelia. The pathogenesis of syringomyelia is discussed. The need to evaluate cervical spinal cord by taking T1 weighted sagittal sections in all the patients of large posterior fossa mass lesions causing obstruction to the outlet foramina of the fourth ventricle has been stressed, in order to detect associated syringomyelia.

Adolescent↗
PubMed2000

Comparison of retroperitoneoscopic nephrectomy with open surgery for tuberculous nonfunctioning kidneys.

PURPOSE: We describe, define and evaluate the role of retroperitoneoscopic nephrectomy for tuberculous nonfunctioning kidneys, and compare the results with those of open nephrectomy in similar cases in a nonrandomized study. MATERIALS AND METHODS: Beginning in July 1994, 9 patients underwent retroperitoneoscopic nephrectomy for tuberculous nonfunctioning kidneys at our center. Data obtained from the records of these patients were compared with those of 9 who underwent open nephrectomy for a similar indication during the same period. Retroperitoneoscopic nephrectomy was initially performed by kidney dissection followed by ligation of the hilar vessels. The technique was subsequently modified and the vessels controlled before dissecting the kidney. Various parameters were compared and statistical analysis was done. RESULTS: The 2 groups were similar in regard to patient age, gender and side of disease. Retroperitoneoscopic nephrectomy was successful in 7 of the 9 patients. Although 2 of our initial patients required conversion to open surgery, the remaining 7 successfully underwent retroperitoneoscopic nephrectomy after modifying the technique. Mean operative time was slightly greater in the retroperitoneoscopy than in the open surgery group (103.3 versus 92.2 minutes). Mean blood loss was less in the retroperitoneoscopy group (101.4 versus 123.3 ml.), mean hospital stay plus or minus standard deviation was significantly shorter (3.2 +/- 0.83 versus 8.88 +/- 3.37 days) and mean time to return to work was significantly less (3 versus 7 weeks). Mean analgesic requirement for opioids and diclofenac sodium was also lower in the retroperitoneoscopic nephrectomy group (0 versus 1.44 +/- 0.72 and 3.8 +/- 1.3 versus 4.3 +/- 1.2 doses, respectively). Minor complications developed in only 2 retroperitoneoscopy cases. CONCLUSIONS: Tuberculosis has been considered a contraindication to retroperitoneoscopic nephrectomy due to a high conversion rate. However, we believe that our modified technique of retroperitoneoscopic nephrectomy is a viable option for managing tuberculous nonfunctioning kidneys. The conversion rate is lower than previously reported. Comparing our results with those of open nephrectomy shows that retroperitoneoscopic nephrectomy is beneficial in all respects except for slightly longer operative time. Because of the benefits of minimally invasive surgery, this approach should be considered in such cases.

Adolescent↗