PubMed Health⌕ Search

Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 469 records · Page 26Linked to original sources
PubMed2001

Probing the machinery of intracellular trafficking with the atomic force microscope.

Atomic force microscopy has emerged as a powerful tool for characterizing single biological macromolecules, macromolecular assemblies, and whole cells in aqueous buffer, in real time, and at molecular-scale spatial and force resolution. Many of the central elements of intracellular transport are tens to hundreds of nanometers in size and highly dynamic. Thus, atomic force microscopy provides a valuable means of addressing questions of structure and mechanism in intracellular transport. We begin this review of recent efforts to apply atomic force microscopy to problems in intracellular transport by discussing the technical principles behind atomic force microscopy. We then turn to three specific areas in which atomic force microscopy has been applied to problems with direct implications for intracellular trafficking: cytoskeletal structure and dynamics, vesicular transport, and receptor-ligand interactions. In each case, we discuss studies which use both intact cellular elements and reconstituted models. While many technical challenges remain, these studies point to several areas where atomic force microscopy can be used to provide valuable insight into intracellular transport at exquisite spatial and energetic resolution.

Biological Transport↗
PubMed2001

Prophylaxis of graft-versus-host disease with cyclosporine-prednisone is associated with increased risk of chronic graft-versus-host disease.

To determine the effect of two different graft-versus-host disease (GVHD) prophylactic regimens--cyclosporine with short course of methotrexate (CYA-MTX) and cyclosporine with prednisone (CYA-PRED)--on the incidence of chronic GVHD (cGVHD), we retrospectively reviewed the outcomes of 196 consecutive allogeneic related blood and marrow transplants performed at our institution utilizing one of these regimens. CYA-PRED was given to patients who were transplanted more recently because of concern about the increased risk of veno-occlusive disease of the liver, increased mucositis, and slower engraftment in patients receiving CYA-MTX. Prophylaxis with CYA-PRED was associated with a higher risk of development of cGVHD (risk ratio (RR) 3.5; 95% confidence intrerval (CI), 2.2-5.4). The proportion of patients with extensive disease among those developing cGVHD was higher in the CYA-PRED group (71%) than in the CYA-MTX group (57%), although this difference was not statistically significant. The cumulative probability of extensive cGVHD at 2 years was higher in the CYA-PRED group (RR 4.2, 95% CI, 2.4-7.4). Development of acute GVHD and cytomegalovirus mismatch were independent predictors of increased risk of cGVHD. We conclude that GVHD prophylaxis with CYA-PRED is associated with a higher overall rate of cGVHD compared to CYA-MTX. The type of GVHD prophylaxis should be considered when comparing the incidence of cGVHD reported in different studies.

Adolescent↗
PubMed2001

Peri-engraftment respiratory distress syndrome during autologous hematopoietic stem cell transplantation.

From 1987 to 1998, 19 of 416 patients (4.6%) who underwent autologous hematopoietic stem cell transplantation experienced peri-engraftment (within 5 days of neutrophil recovery) respiratory distress syndrome (PERDS) not attributable to infection, fluid overload, or cardiac dysfunction. The median time from stem cell infusion to onset of PERDS was 11 days (range 4-25). Risk of PERDS or its outcome was not predicted by any pre- or peri-transplant clinical or laboratory feature. The respective median white blood cell and platelet counts at first symptoms were 1.3 x 10(9)/l and 25 x 10(9)/l. No patients had an infectious etiology by bronchoalveolar lavage. Six of the 19 patients had alveolar hemorrhage, which was significantly correlated with high neutrophil count. PERDS was directly implicated in four deaths (21%). Eleven patients received high-dose corticosteroid therapy, including five of the six who required mechanical ventilation. Ten of these patients experienced clinical improvement, which occurred within 24 h in five. The rapid response to corticosteroid treatment and the fact that such therapy was delayed until after intubation in all the mechanically ventilated cases point to a therapeutic benefit.

Adolescent↗
PubMed2001

High incidence of gastrointestinal tract bleeding after autologous stem cell transplant for primary systemic amyloidosis.

Peripheral blood stem cell transplants have been associated with better response rates than conventional chemotherapy in patients with primary systemic amyloidosis. A higher incidence of gastrointestinal (GI) tract bleeding has been observed among amyloidosis patients undergoing peripheral stem cell transplantation. We retrospectively reviewed the medical records of such patients to identify those who had GI tract bleeding in the post-transplant period. Forty-five patients were studied. Nine patients had GI tract bleeding in the post-transplant period. The median post-transplant duration to onset of bleeding was 9.5 days (range 1 to 48 days). Three patients had lower GI tract bleeding, two had upper GI tract bleeding, and four had both. Diffuse esophagitis and gastritis were the most common findings on endoscopy. There were no correlations among the age, platelet nadir, or CD34 count of the graft and the risk of bleeding. Women were more likely to have GI tract bleeding (P = 0.015), as were patients with slow platelet engraftment (P = 0.02). Patients with multiorgan involvement and those on hemodialysis appeared to be at a higher risk of GI tract bleeding. The mean post-transplant hospital stay for those with GI tract bleeding was 37 days compared with 14.5 days for those who did not have GI tract bleeding (P = 0.0047).

Adult↗
PubMed2001

Effect of slow lymphocyte recovery and type of graft-versus-host disease prophylaxis on relapse after allogeneic bone marrow transplantation for acute myelogenous leukemia.

Allogeneic BMT is potentially curative for patients with acute myelogenous leukemia (AML) in first remission. However, many patients relapse after transplantation. Various immunotherapeutic options have been attempted with variable success in preventing relapse. Early identification of patients at high risk for relapse could allow prompt intervention. We examined the effect of slow lymphocyte recovery after sibling-matched allogeneic BMT on the risk of relapse in patients with AML. We also examined the effect of prednisone-containing GVHD prophylaxis on the rate of lymphocyte recovery. Patients with absolute lymphocyte count (ALC) <150 x 10(6)/l by day +30 had a 3.5-fold higher risk of relapse (P = 0.0088) and a lower overall survival (P = 0.0079) than patients with a higher ALC. We did not find correlation between lymphocyte count determined earlier in the post-transplantation course (day +21) and the risk of relapse. Patients receiving prednisone had a significantly lower ALC at day +30 than those who did not receive prednisone (289 vs 549 x 10(6)/l, P = 0.002). We conclude that a slow lymphocyte recovery after allogeneic BMT for AML is strongly predictive of subsequent relapse and that the type of GVHD prophylaxis should be considered when analyzing lymphocyte recovery.

Adolescent↗
PubMed2001

Charcoal hemofiltration for hepatic veno-occlusive disease after hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT) results in considerable morbidity and mortality. No therapy has been shown to be uniformly effective. Several studies have highlighted the pivotal role of endothelial injury and the hemostatic system in the pathogenesis of HVOD. Charcoal hemofiltration has been shown to be effective for adsorbing circulating bilirubin and other protein-bound toxins and for supporting patients in hepatic failure. We describe two adult patients with severe, biopsy-proven HVOD (peak bilirubin levels, more than 50 mg/dl in both cases) after HSCT who were successfully treated with charcoal hemofiltration after other treatments failed (including defibrotide in one patient). Both patients were heavily treated before they underwent either autologous (melphalan and total body irradiation conditioning) or allogeneic (cyclophosphamide and total body irradiation conditioning) HSCT. Additional studies are warranted to confirm this preliminary observation and investigate the mechanism of action.

Adult↗
PubMed2001

STRICA, a novel Drosophila melanogaster caspase with an unusual serine/threonine-rich prodomain, interacts with DIAP1 and DIAP2.

The recently published genome sequence of Drosophila melanogaster predicts seven caspases in the fly. Five of these caspases have been previously characterised. Here, we describe the Drosophila caspase, STRICA. STRICA is a caspase with a long amino-terminal prodomain that lacks any caspase recruitment domain or death effector domain. Instead, the prodomain of STRICA consists of unique serine/threonine stretches. Low levels of strica expression were detected in embryos, larvae, pupae and adult animals. STRICA is a cytoplasmic protein that, upon overexpression, caused apoptosis in cultured Drosophila SL2 cells that was partially suppressed by DIAP1. Interestingly, unlike other fly caspases, STRICA showed physical association with DIAP2, in cotransfection experiments. These results suggest that STRICA may have a unique cellular function.

Amino Acid Sequence↗
PubMed2001

Vascular gene transfer driven by endoglin and ICAM-2 endothelial-specific promoters.

The involvement of the vascular endothelium in a large number of diseases supports the importance of vascular-specific gene delivery for their treatment. The hereditary hemorrhagic telangiectasia type 1 is an example of a vascular inherited disease (OMIM 187300). This is an autosomal dominant vascular disorder originated by mutations in the endoglin gene and associated with frequent epistaxis, telangiectases, gastrointestinal bleedings, and arteriovenous malformations in brain, lung and liver. Here, we address for the first time the possibility of using in vivo gene transfer to target endoglin expression to the vasculature. The promoter of the endothelial gene, ICAM-2, was used to generate transgenic animals which demonstrated endothelial expression of endoglin. Next, the promoters of the human endothelial genes, endoglin and ICAM-2, were inserted upstream of the human endoglin cDNA, and the resulting constructs were systemically or locally delivered, demonstrating endoglin expression in the vessel walls of liver, lung and skin. These gene transfer experiments represent an initial step in the treatment of the hereditary hemorrhagic telangiectasia type 1 by gene therapy, and suggest that endoglin and ICAM-2 promoters can be used to deliver other genes to the endothelium specifically.

Animals↗
PubMed2001

Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine.

MuStDO 5 is a multivalent plasmid DNA vaccine for malaria comprised of five plasmid DNAs encoding five proteins from Plasmodium falciparum and one plasmid DNA encoding human GM-CSF. To evaluate the safety of MuStDO 5, a series of pre-clinical studies were conducted in mice and rabbits. In pharmacology studies in mice, GM-CSF could not be detected in the serum following either intramuscular or a combined intramuscular/intradermal administration of the vaccine, but was readily detected in the muscle following intramuscular administration. In a tissue distribution study in mice, MuStDO 5 plasmid DNA was detected by PCR initially in highly vascularized tissues, while at later time-points the plasmid DNA was detected primarily at the site(s) of injection. In GLP safety studies in mice and rabbits, repeated intramuscular/intradermal administration of the MuStDO 5 vaccine was found to be safe and well tolerated without any evidence of autoimmune pathology.

Adjuvants, Immunologic↗
PubMed2001

Hereditary palmoplantar keratoderma (four cases in three generations).

A 39-year-old man reported with progressive thickening of the skin of the hands and feet and an inability to flex his hand. It was largely asymptomatic; however, brisk walking caused excessive sweating, pain, and widening of the fissures on the soles of the feet. He was unable to walk barefooted. According to his mother, the first episode presented with blistering at 7 days of age. Ever since, the condition has steadily worsened to acquire the current status. He was married at the age of 18 years, and had a stillborn child 18 months afterwards. Presently, he has three children, two girls aged 14 and 12 years and a son aged 10 years. Both the daughters are similarly affected. While cataloguing the details of the pattern of inheritance, the mother of the index case was also found to be affected (Fig. 1). The natural history of the disease was identical. Examination of the palms was marked by pronounced thickening of the skin resulting in the masking of palmar creases. The thickening was well demarcated and its margins were prominent and surrounded by an erythematous halo. The color of the skin was yellow and waxy (Fig. 2a). Contractures were present on all the fingers; nevertheless, the deformity of the middle and distal interphalangeal joints of the little finger was prominent. The soles of the feet had a similar morphology. In addition, marked fissuring was obvious (Fig. 2b). His daughters had an identical affliction of the palms and soles. The texture and morphology of the nails were normal. Light microscopy performed on scrapings from the fissures, mounted on 10% potassium hydroxide, revealed mycelia (hyphae) and spores. Hematoxylin and eosin-stained microsections from the palms and soles showed exquisite changes in the epidermis characterized by considerable uniform orthohyperkeratosis. Hypergranulosis and acanthosis were other associated changes. In addition, perinuclear vacuolization and keratohyalin granules of varying sizes and shapes were located at the periphery of the cells. A sparse mononuclear infiltrate was located at the dermo-epidermal junction. Hyphae and spores of fungi were also identified in the stratum corneum (Fig. 3). Itraconazole, 400 mg/day in two equally divided doses, was administered with major meals for 7 days. In addition, high doses of vitamin A (100,000 IU) were given daily for 2 weeks, supplemented by 12% salicylic acid (Salicylix SF12) ointment for daytime application and an ointment containing 6% coal tar and 3% salicylic acid (Salytar) for night-time application. This treatment is useful in recalcitrant cases.

Adolescent↗
PubMed2001

Sources of preventable errors related to transfusion.

BACKGROUND AND OBJECTIVES: Transfusion errors always remain under-reported owing to a lack of awareness about transfusion-related adverse events among the hospital staff and an inadequate feedback system in most of the transfusion centres. This article reports the results obtained from a study carried out to investigate the sources and types of errors in our tertiary care hospital. MATERIALS AND METHODS: The errors reported by the blood bank staff (i.e. reception counter clerical and technical staff) and the residents in charge of the patient, were studied over a period of 1 year (from May 1998 to April 1999) and classified based on the site of occurrence. RESULTS: A total of 123 errors were detected over the 1-year study period. Of these 123 errors, 107 (86.99%) occurred outside the blood bank and 16 (13%) in the blood bank. CONCLUSION: Errors occur most frequently outside the blood bank, and the bedside of the patient is the main location.

Blood Banks↗
PubMed2001

Anorexia nervosa in an elderly woman.

OBJECTIVE: To demonstrate a case of anorexia nervosa in the elderly and to highlight the need for broadening of current diagnostic criteria. CLINICAL PICTURE: First onset of anorexia nervosa in a 72-year-old woman following bereavement of her husband. TREATMENT: Nine treatments of electroconvulsive therapy. OUTCOME: Treatment resulted in remission of the depressive symptoms and improvement of eating behaviour. CONCLUSIONS: Anorexia nervosa does occur in the elderly and can be difficult to detect. Where comorbid depression exists it requires aggressive treatment.

Aged↗
PubMed2001

Intra-arterial embolization of lumbar artery pseudoaneurysm following percutaneous nephrolithotomy.

The management of a patient with haematuria following percutaneous nephrolithotomy is described. The patient underwent renal angiography to assess the cause of bleeding. A pseudoaneurysm arising from first left lumbar artery was incidentally discovered, which was then successfully embolized using an indigenously fabricated metallic coil and gel foam particles in the same sitting.

Aneurysm, False↗
PubMed2001

Hormone replacement therapy for postmenopausal women with diabetes.

BACKGROUND: Recent studies have shown only 17% of postmenopausal women in the UK receive prescriptions for hormone replacement therapy (HRT), with diabetic women being prescribed HRT 30% less often than non-diabetic women. Up to 80% of women experience menopausal symptoms, however, so it is expected that by using HRT many would gain benefit from symptom relief, in addition to benefiting from its effects in disease prophylaxis. METHODS: We conducted a questionnaire survey of the attitudes to HRT prescribing of 178 local general practitioners (GPs) and 47 hospital doctors, working in diabetes and gynaecology. RESULTS: Responses were received from 98 (55%) GPs and 39 (83%) hospital doctors. One hundred and thirty-six (99%) would advise HRT for menopausal symptoms, with 133 (97%) advising HRT for a spontaneous premature menopause and 126 (92%) for a surgically induced menopause. One hundred and thirty-four (98%) would advise HRT for diabetic women with menopausal symptoms, with 122 (89%) indicating that HRT had no adverse effect on glycaemic control. For disease prophylaxis, all hospital doctors and 93 (95%) GPs would advise HRT for prevention of osteoporosis, although only 91 (93%) GPs would advise HRT to diabetic women for this indication. Thirty-three (85%) hospital doctors would advise HRT as prophylaxis against cardiovascular disease compared with 66 (67%) of GPs. For this indication in diabetic women, 32 (82%) hospital doctors and 67 (68%) GPs would advise HRT. Oral HRT was the most widely recommended preparation although GPs also frequently recommended patches. Topical gel, implants and other preparations were less commonly advised. Hospital doctors predominantly advised HRT for menopausal symptoms to be continued for between 1 and 5 years, although more GPs recommended HRT to be continued for longer than 5 years. The majority of doctors from both groups advised that HRT used for disease prophylaxis be continued for more than 5 years. CONCLUSION: More doctors than anticipated indicated they would recommend HRT, especially to diabetic women. Concerns among doctors about the side-effects of HRT and, in particular, the metabolic effects of HRT, do not appear to deter them from advising HRT. Willingness to prescribe a drug, however, is different from actually prescribing it and responses to questionnaires tend to be those regarded as being acceptable. Low patient demand for HRT due to fear or lack of awareness may also be contributing. Organizational change with the development of more menopause clinics may facilitate wider use of HRT.

Attitude of Health Personnel↗