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Biomedical subjects

R Saxena

Publications and source records attributed to R Saxena.

At least 19 recordsLinked to original sources
PubMed1999

A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression.

Two novel polymorphisms in the distal regulatory region of the MCP-1 gene were identified by directly sequencing PCR amplified genomic DNA. These polymorphisms are located at positions -2518 (G or A) and -2076 (A or T) relative to the major transcriptional start site of the gene. To examine the effect of these polymorphisms on MCP-1 transcription, polymorphic variants of the MCP-1 distal regulatory region were placed upstream of a luciferase reporter gene and transfected into A172 cells. IL-1beta-induced luciferase activity was significantly greater from cells transfected with constructs containing G at position -2518. The polymorphism at -2076 did not affect MCP-1 transcription. IL-1beta-treated peripheral blood mononuclear cells from individuals heterozygous or homozygous for G at -2518 produced more MCP-1 than cells from individuals homozygous for A at -2518. These data identify a polymorphism in the MCP-1 distal regulatory region that affects the level of MCP-1 expression in response to an inflammatory stimulus.

Alleles↗
PubMed1999

Role of NK and T cells in IL-12-induced anti-tumor response against hepatic colon carcinoma.

IL-12 is an immuno-regulatory cytokine that has been shown to generate a potent NK and Th1 response in a variety of laboratory models. However, the detailed immune development in the hepatic tumor model by IL-12-mediated gene therapy has not been clarified. In our previous study, intra-tumoral transfer of Adv.mIL-12 (5 x 10(8) pfu) to the MCA26 colon carcinoma liver tumor induced an effective anti-tumor response, extending the median survival time from 29 to over 54 days, while 25% of the animals became tumor-free after a single treatment. In this work, we show that NK cells are responsible for the early, and both NK and T cells for the long-term, Adv.mIL-12-induced immune response. Immunohistopathological analysis of the tumor and in vitro cytotoxicity study of the mononuclear cells of the liver show that NK cells are the first to infiltrate and mediate tumor cell killing, as early as 48 hr after Adv.mIL-12 treatment. In vivo and in vitro depletion of these cells completely abolishes this early anti-tumor response. This activity can be observed in both populations of conventional NK and NKT cells in vitro and in athymic nude mice in vivo. However, the early NK response alone is not sufficient. In vivo T-cell depletion in both the primary tumor treatment and the long-term survival rechallenge study reveals that T cells in addition to NK cells are required in the development of the long-term survival and immunity attributed to Adv.mIL-12 gene therapy in this orthotopic tumor model of colon carcinoma.

Adenoviridae↗
PubMed1999

Gene therapy to promote thromboresistance: local overexpression of tissue plasminogen activator to prevent arterial thrombosis in an in vivo rabbit model.

Tissue-type plasminogen activator (tPA) catalyzes the rate-limiting initial step in the fibrinolytic cascade. Systemic infusion of tPA has become the standard of care for acute myocardial infarction. However, even the relatively short-duration protocols currently employed have encountered significant hemorrhagic complications, as well as complications from rebound thrombosis. Gene therapy offers a method of local high-level tPA expression over a prolonged time period to avoid both systemic hemorrhage and local rebound thrombosis. To examine the impact of local tPA overexpression, an adenoviral vector expressing tPA was created. The construct was characterized functionally in vitro, and the function of the vector was confirmed in vivo by delivery to the rabbit common femoral artery. Systemic coagulation parameters were not perturbed at any of the doses examined. The impact of local overexpression of tPA on in vivo thrombus formation was examined subsequently in a stasis/injury model of arterial thrombosis. The construct effectively prevented arterial thrombosis in treated animals, whereas viral and nonviral controls typically developed occluding thrombi. This construct thus offers a viable technique for promoting a locally thromboresistant small-caliber artery.

Adenoviridae↗
PubMed1999

Risk factors for thrombosis in nonembolic cerebrovascular disease.

Thirty-seven young patients (less than 42 years of age) presenting with sudden onset of idiopathic nonembolic cerebrovascular disease were evaluated for underlying prothrombotic factors. Activated protein C resistance (APC-R) was measured by Dahlback's method and the modified method using factor V-deficient plasma. Activities of antithrombin (AT) III, protein C and S were measured. Anticardiolipin antibody was estimated by ELISA and lupus anticoagulant by kaolin clotting tests. APC-R was the most common defect (21.62%) followed by AT III deficiency and presence of anticardiolipin antibodies (5.6% each). The latter two were present together in one case. It is thus concluded that APC-R is the most common defect underlying idiopathic nonembolic cerebrovascular infarction in young individuals.

Activated Protein C Resistance↗
PubMed1999

Epikeratoplasty for traumatic corneal ectasia.

PURPOSE: To evaluate the efficacy of epikeratoplasty in a case of traumatic corneal ectasia. METHOD: Epikeratoplasty using a manually dissected donor lenticule was used to treat traumatic corneal ectasia after an iron nail injury. RESULT: No intra- or postoperative complication was encountered. At the end of 6 months' follow-up, the patient's best corrected visual acuity was 6/12. CONCLUSION: Epikeratoplasty is a useful technique to treat traumatic corneal ectasia.

Child↗
PubMed1999

Clinico-haematological profile of isolated PF3 availability defect: therapeutic potential of soya bean--a pilot study.

Isolated platelet factor 3 (PF3) availability defect has been observed to be a common platelet functional disorder (PFD) in the Department of Haematology, All India Institute of Medical Sciences, New Delhi, India. One hundred and thirty-two patients were diagnosed to have this defect based on the presence of reduced PF3 availability, normal platelet aggregation with ADP, collagen, adrenaline, ristocetin, and arachidonic acid and normal PF3 content. PF3 availability was evaluated by measurement of Russel viper venom time (RVVT) on the patient's platelet-rich plasma (PRP) after incubation with ADP for 20 min. An RVVT value >19.0 s was considered diagnostic of reduced PF3 availability in patients with normal prothrombin and activated partial thromboplastin times. Isolated PF3 availability defect occurred in patients with ages between 2 and 65 yr and had a female preponderance (M:F=1:2). One fifth of the patients had a positive family history of similar mild bleeding diathesis, indicating an autosomal dominant pattern of inheritance. All patients presented with mild bleeding manifestations, the commonest symptom being appearance of recurrent ecchymotic spots. In females, menorrhagia was the commonest symptom. A pilot study was conducted on 45 patients to evaluate the therapeutic role of oral soya bean (50 g/d). The clinical response was evaluated after 3 months. Soya therapy resulted in disappearance of bleeding problems in 5 patients and reduction in frequency and severity of bleeding in 26 patients. A repeat PF3 availability test after 3 months of therapy showed complete correction in 4 and partial correction in 12 patients. It is evident from McNemer's test that both the clinical and the laboratory parameters (PF3 availability) showed a similar response to soya therapy (p>0.05). Pre-soya therapy mean PF3 availability values differ significantly from those after soya therapy (p<0.01). Thus, soya bean appears to have a therapeutic potential in isolated PF3 availability defect.

Adenosine Diphosphate↗
PubMed1999

Partial hepatectomy-induced polyploidy attenuates hepatocyte replication and activates cell aging events.

In understanding mechanisms of liver repopulation with transplanted hepatocytes, we studied the consequences of hepatic polyploidization in the two-thirds partial hepatectomy model of liver regeneration. Liver repopulation studies using genetically marked rodent hepatocytes showed that the number of previously transplanted hepatocytes did not increase in the liver with subsequential partial hepatectomy. In contrast, recipients undergoing partial hepatectomy before cells were transplanted showed proliferation in transplanted hepatocytes, with kinetics of DNA synthesis differing in transplanted and host hepatocytes. Also, partial hepatectomy caused multiple changes in the rat liver, including accumulation of polyploid hepatocytes along with prolonged depletion of diploid hepatocytes, as well as increased senescence-associated beta-galactosidase and p21 expression. Remnant hepatocytes in the partially hepatectomized liver showed increased autofluorescence and cytoplasmic complexity on flow cytometry, which are associated with lipofuscin accumulation during cell aging, and underwent apoptosis more frequently. Moreover, hepatocytes from the partially hepatectomized liver showed attenuated proliferative capacity in cell culture. These findings were compatible with decreased proliferative potential of hepatocytes experiencing partial hepatectomy compared with hepatocytes from the unperturbed liver. Attenuation of proliferative capacity and other changes in hepatocytes experiencing partial hepatectomy offer novel perspectives concerning liver regeneration in the context of cell ploidy.

Animals↗
PubMed1999

Epidemiology of cataract in India: combating plans and strategies.

Blindness due to cataract presents an enormous problem in India not only in terms of human morbidity but also in terms of economic loss and social burden. The WHO/NPCB (National Programme for Control of Blindness) survey has shown that there is a backlog of over 22 million blind eyes (12 million blind people) in India, and 80.1% of these are blind due to cataract. The annual incidence of cataract blindness is about 3.8 million. The present annual level of performance is in the order of about 1.6-1.9 million cataract operations. To clear the backlog of cataract cases by the year 2000 and to tackle the rising incidence, 5-6 million cataract operations annually will have to be performed as against the present rate of 1. 7 million per year. India is undertaking a new long-term initiative to expand the capability of cataract surgery and service levels with financial assistance from the World Bank. An important feature of this initiative is the attention given to spread the cataract blindness programme in rural and tribal areas. The second feature is the emphasis placed on modern extracapsular cataract extraction with intra-ocular lens implantation as the preferred surgical technique. Another noteworthy feature is developing institutional capacity and appropriate co-ordination mechanisms for collaboration between the non-government organization and the public sector to expand coverage to the most disadvantaged populations. The fourth and the most important strategy is to carry out intensive campaigns at the state and national levels against cataract blindness in order to substantially increase the demand for cataract services. A country like India has more significance for such a plan in view of the fact that various social, economic and environmental factors contribute to cataract blindness in populations at a much younger age.

Blindness↗
PubMed1999

Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke.

BACKGROUND AND PURPOSE: Diaspirin cross-linked hemoglobin (DCLHb) is a purified, cell-free human hemoglobin solution. In animal stroke models its use led to a significant reduction in the extent of brain injury. The primary objective of this study was to evaluate the safety of DCLHb in patients with acute ischemic stroke. METHODS: DCLHb or saline was administered to 85 patients with acute ischemic stroke in the anterior circulation, within 18 hours of onset of symptoms, in a multicenter, randomized, single-blind, dose-finding, controlled safety trial, consisting of 3 parts: 12 doses of 25, 50, and 100 mg/kg DCLHb over 72 hours. RESULTS: DCLHb caused a rapid rise in mean arterial blood pressure. The pressor effect was not accompanied by complications or excessive need for antihypertensive treatment. Two patients in the 100 mg/kg group had adverse events that were possibly drug related: one suffered fatal brain and pulmonary edema, the other transient renal and pancreatic insufficiency. Multivariate logistic regression analysis showed that a severe stroke at baseline and treatment with DCLHb (OR, 4.0; CI, 1.4 to 12.0) were independent predictors of a worse outcome (Rankin Scale score of 3 to 6) at 3 months. CONCLUSIONS: Outcome scale scores were worse in the DCLHb group, and more serious adverse events and deaths occurred in DCLHb-treated patients than in control patients. We recommend that additional safety studies be performed, preferably with a second generation, genetically engineered hemoglobin.

Acute Disease↗
PubMed1998

Gall bladder cancer: proposal for a modification of the TNM classification.

Gall bladder cancer is the commonest biliary tract malignancy. The TNM classification of AJCC-UICC is the most widely accepted and most commonly used system for staging. We propose some modifications in the existing classification and recommend guidelines for management based on the stage of the disease.

Gallbladder Neoplasms↗