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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 1,117 records · Page 62Linked to original sources

Immunological characteristics of a recombinant hepatitis B virus-derived multiple-epitope polypeptide: a study in polyvalent vaccine design.

Immunological properties of a model polyepitope immunogen (MEP-1) consisting of selected determinants from envelope proteins of hepatitis B virus (HBV) were examined. Immunization with MEP-1 induced high-titre antibodies in a variety of murine strains and in rabbits although an overall hierarchy of B-cell immunodominance was observed as pre-S1-derived > S-derived > pre-S2-derived segments. Anti MEP-1 antibody responses in all hosts were found to be exclusive for HBV-derived sequences in the absence of any fraction directed against the various interepitope junctions. With panels of overlapping peptides it was observed that the anti-pre-S1 and anti-pre-S2 components of anti-MEP-1 antibodies were, in all animals tested, of the desired specificity from the standpoint of potential virus-neutralizing ability. The MEP-1 segment representing residues 124-127 of the major protein of hepatitis B surface antigen (HBsAg) was found to elicit a conformation-specific antibody response. Furthermore, this subpopulation was either predominantly or exclusively against the Met133-Lys141-dependent group-specific epitope. Finally, the HBV sequences in MEP-1 were shown to retain their Th-cell activities. These studies suggest that MEP-1 provides a useful tool in the study of polyvalent vaccine design.

Amino Acid Sequence↗

Assessment of the effect of the toxicity of a textile dye on Nostoc muscorum ISU, a diazotrophic cyanobacterium.

The impact of graded concentrations (5, 10, 15 and 20 mg dm(-3) of acid mordant Metomega Chrome Orange GL, a common dye used in woollen, carpet and textile industries, was studied on protein and pigment content and photosynthetic oxygen evolution in a diazotrophic cyanobacterium Nostoc muscorum. The lower concentration of 5 mg dm(-3) showed a negligible effect on protein and pigment content and photosynthetic oxygen evolution, whereas at higher concentrations a drastic decrease in the above parameters was observed. The highest concentration of 20 mg dm(-3) resulted in a decrease of protein, chlorophyll a, phycocyanin and carotenoid content by 72, 76, 54 and 17% of the control, respectively. Photosynthetic oxygen evolution also decreased by 92% of the control at this concentration of the dye.

Journal Article↗

Postnatal development of NMDA, AMPA, and kainate receptors in individual layers of rat visual cortex and the effect of monocular deprivation.

The postnatal development of the ligand binding to N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and kainate receptor sites was studied in individual layers of rat visual cortex with [3H]MK-801, [3H]CNQX and [3H]kainate, respectively. The studies were performed by quantitative receptor autoradiography in the different visual cortical layers from normally raised rats and from monocularly deprived animals. In normally raised rats, in all visual cortical layers, [3H]MK-801 and [3H]CNQX binding increased significantly from birth to around postnatal day 20, at which age already the adult values are reached. In contrast, the increase in [3H]kainate binding from day 1 to day 15 is followed by a significant decrease in binding sites up to day 25; at this age the adult binding level is nearly attained. Monocular deprivation, by unilateral eyelid suture at the age of 11 days onwards, leads to a transient decrease in [3H]CNQX binding in all visual cortical layers, whereas [3H]kainate binding results to a permanent decrease in AMPA receptor sites in cortical layers II to VI in both sides of the cortex. In contrast, only long-term monocular deprivation until the age of 90 days resulted in decreased [3H]MK-801 binding levels as compared to age-matched controls. The data suggest that the laminar development of glutamate receptor subtypes is differentially affected by visual experience during early brain maturation.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Plant transposable elements and the genome.

Transposable elements are ubiquitous in the plant kingdom and share many common features, both structural and mechanistic, with mobile elements from other eukaryotes. Transposition of these elements can influence plant genes and genomes in many ways. It is also becoming clear that transposable element derived sequences can be a major component of plant genomes. These sequences are probably, therefore, very significant factors in plant evolution.

Biological Evolution↗

Ureterovaginal fistula: an unusual complication of stone fragments after extracorporeal shock wave lithotripsy in situ.

We report a case of impaction of stone fragments in the lower ureter after extracorporeal shock wave lithotripsy in situ of an upper ureteral calculus resulted in a ureterovaginal fistula. Ureteroscopic retrieval of fragments and stenting provided symptomatic relief. The pathogenesis of this complication, which to our knowledge has not been reported previously, is discussed.

Adult↗

Should upper ureteral calculi be manipulated before extracorporeal shock wave lithotripsy? A prospective controlled trial.

Whether all upper ureteral stones must be manipulated before extracorporeal shock wave lithotripsy (ESWL*) is an ongoing controversy. In a prospective trial, symptomatic patients with solitary upper ureteral calculi less than 1 year in duration were alternated between ESWL in situ and pre-ESWL stone manipulation. Pretreatment excretory urograms were assessed for stone size and degree of proximal hydroureteronephrosis, which was graded from zero (no dilatation) to 3 (severe dilatation). Stone manipulation was done with the patient under intravenous sedation and local anesthesia. A total of 4,000 shock waves was given in a single session using Siemens Lithostar Plus, and treatment was repeated on days 4, 15 and 30 if required. The patients were evaluated 3 months after onset of therapy with excretory urogram and urine culture. Seventy patients qualified for the study (group 1-35 in situ and group 2-35 stone manipulation) and were comparable in relation to age and sex, stone size and degree of hydronephrosis. There was no significant difference between the 2 groups regarding the number of sessions (group 1-1.86 +/- 1.2 and group 2-2.03 +/- 1.2) or shock wave requirement (group 1-5,705.8 +/- 3,536.9 and group 2-5,549.1 +/- 3,837.2) for stone fragmentation. The degree of proximal dilatation did not contribute significantly towards the outcome (F ratio 0.675, p = 0.57). A total of 30 patients (85.5%) in group 1 had a satisfactory outcome at 3 months, while 3 (8.5%) had significant residual calculi and 2 stones could not be fragmented. Of the manipulated stones 33 (94%) were successfully cleared, while 2 patients required auxiliary procedures. Ureteroscopy was required in 1 patient for upward migration of the stent. Morbidity in both groups was comparable. We conclude that upper ureteral stones should be treated in situ to avoid the morbidity of manipulation.

Adult↗

Lowered expression of C3b receptor (CR1) on erythrocytes of rheumatoid arthritis patients.

The number of C3b receptors (CR1) on erythrocytes (E) has been quantitated by whole cell enzyme-linked immunosorbent assay (ELISA), using a monoclonal anti-CR1 antibody, in 46 healthy individuals as controls, 58 having rheumatoid arthritis (RA) and 3 hereditary angioedema patients. The mean value of CR1 in RA (381/E) was significantly lower (p < 0.001) when compared to normal controls (646/E). In hereditary angioedema patients CR1 numbers (620/E) were found to be comparable to normal values. No significant difference was found between normal male (708/E) and female (598/E) subjects. Among the patient groups, those on steroid therapy (352/E) showed no change compared to others not receiving such therapy (408/E). The cumulative frequency curve of CR1 in the normal population showed maximum inflection at 32% and 82%. This led us to conclude that there is a trimodal distribution of receptors in the control population. Such a contention is well supported by frequency histogram, when a small group interval (0-50) was chosen. However, if large group intervals (0-100 or 0-150) were considered, a very close approximation to unimodal pattern was obtained. The factors actually contributing to low receptor numbers are yet to be elucidated.

Adolescent↗

Lipoprotein glomerulopathy: first report in a Chinese male.

Only seven patients with lipoprotein glomerulopathy have been reported, all in Japanese subjects. We describe the first Chinese patient with lipoprotein glomerulopathy, a 28-year-old man followed for 8 years. As in all patients described thus far, our patient has hyperlipoproteinemia phenotypically similar to the familial type III hyperlipoproteinemia, a high serum level of apolipoprotein E (apo E) (but with the heterozygous E 2/3 isoform instead of the E 2/2 isoform), and the absence of the typical clinical features associated with type III hyperlipoproteinemia. The common clinical presentation is the nephrotic syndrome. The characteristic pathologic features are concentrically layered vacuolated lipid "thrombi" in distended glomerular capillary lumens that contain beta/pre-beta lipoprotein. Immunofluorescence studies demonstrate lipoprotein "thrombi" staining for apo E and apo B, but not apo A-I, apo A-II, or apo J. Immunoglobulins, complement, and fibrin are absent or present in trace amounts. The long-term follow-up demonstrates progressive deterioration of renal function despite lipolytic therapy. The apparent predilection of lipoprotein glomerulopathy in Orientals, particularly Japanese subjects, is poorly understood, but appears to be related to genetic factors. The cause of the hyperlipoproteinemia and lipoprotein "thrombi" containing apo E and apo B is unknown, but is possibly related to defective receptor-binding mechanisms.

Adult↗

Different binding mode in AT and GC sequences for unfused-aromatic dications.

We have previously synthesized a 2,5-diphenylfuranamidine dication (4) and presented evidence that this compound binds to AT sequences in DNA by a minor-groove interaction mode but binds to GC sequences by intercalation (1,2). To probe these sequence-dependent binding modes in more detail, and particularly to obtain additional evidence for the binding mode in GC rich sequences, we have synthesized and studied the DNA complexes of 1-3 which have the furan ring of 4 replaced by 2,6-substituted pyridine (1), pyrimidine (2), or triazine (3) ring systems. The three compounds with a six-membered central ring system bind to AT DNA sequences more weakly than the furan compound, but retain the minor-groove binding mode. The pyridine and pyrimidine derivatives bind to GC sequences of DNA more strongly than the furan, but the triazine derivative binds more weakly. The aromatic proton signals of 1-3, as previously observed with 4 shift upfield by approximately 0.5 ppm or greater on complex formation with polyd(G-C)2. This and other spectroscopic as well as viscosity and kinetics results indicate that 1-4 bind to GC sites in DNA by intercalation. A nonclassical intercalation model, with the twisted-unfused, aromatic ring system intercalated into an intercalation site of matching structure can explain all of our and the literature results for the GC binding mode of these unfused, aromatic compounds.

Base Sequence↗

Significance of antithyroglobulin autoantibodies in differentiated thyroid carcinoma.

The incidence of antithyroglobulin autoantibodies (ATA) was 17.7% in 963 patients (who attended the clinic from 1981 to 1990) with differentiated thyroid carcinoma (DTC). Another 12 patients developed ATA for a transient period after the treatment with radioiodine. The prevalence of ATA in females (21.5%, 123/572) was significantly higher (p < 0.001) than that seen in males (12.0%, 47/391). Age-dependent occurrence of ATA was not seen for the various age decades. The ATA was more prevalent (p < 0.01) with the papillary type of tumor (118/564) as compared to the follicular variety (51/398). ATA did not influence the metastatic spread of the tumor at the initial presentation (105/170 for the ATA-positive group and 445/793 for the ATA-negative group). However, within the group with metastases, 82.9% (87/105) of patients had local spread into the neck in the presence of ATA, which was significantly higher (p < 0.01) than that seen for patients without ATA (63.8%, 284/445). For assessment of the influence of ATA on the outcome of the disease, the data from 222 patients (46 positive and 176 negative for ATA), with a minimum follow-up of 5 years (mean follow-up of 7.4 years), was considered suitable for analysis. The outcome of the disease was comparable in the presence and the absence of ATA (38/46 and 137/176 patients became disease-free in ATA-positive and -negative groups, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Anti-endotoxin therapy in primate bacteremia with HA-1A and BPI.

OBJECTIVE: The in vivo neutralizing activities of an anti-lipopolysaccharide (LPS) antibody HA-1A (Centoxin [Centocor, Malvern, PA]), a human immunoglobulin M monoclonal antibody, and of bactericidal/permeability-increasing protein (BPI), an endogenously produced human LPS-neutralizing protein, were studied in a primate model of lethal Escherichia coli bacteremia. SUMMARY BACKGROUND DATA: HA-1A has been used with variable success against LPS activity in some animal models and in a recently reported clinical trial. However, no data assessing the efficacy of this agent in subhuman primates is available. Bactericidal/permeability-increasing protein is a product of polymorphomononuclear cells (PMNs) that is stored in azurophilic granules and exhibits LPS-neutralizing activity in vitro and in some in vivo models. METHODS: Immediately after E. coli infusion and in a blinded fashion, three baboons were treated with BPI (5 mg/kg bolus infusion and 95 micrograms/kg/min infusion over 4 hr). Three animals received 3 mg/kg BW of HA-1A, whereas another three baboons received a placebo treatment. RESULTS: The BPI-treated animals demonstrated significantly (p < 0.03) lower circulating LPS-limulus amoebocyte lysate (LAL) activity compared with the control animals, but this reduction in LPS-LAL activity was not associated with improved survival. HA-1A treatment did not reduce LPS-LAL activity. However, both BPI and HA-1A treatment did attenuate the pro-inflammatory cytokine response. CONCLUSION: The current data suggests that incomplete neutralization of endotoxin activity does not alter mortality from severe bacteremia. Given the diversity of mediator production under such circumstances, a strategy of combination therapy in the form of anti-lipopolysaccharide and anticytokine treatment may be necessary to achieve optimal survival.

Amino Acid Sequence↗

Chemopreventive action by an extract from Ocimum sanctum on mouse skin papillomagenesis and its enhancement of skin glutathione S-transferase activity and acid soluble sulfydryl level.

We report the chemopreventive property of an ethanolic extract of the leaves of Ocimum sanctum (a traditional medicinal plant) on 7,12-dimethylbenz[a]anthracene induced skin papillomagenesis in male Swiss albino mice. A significant reduction in the values of tumor incidence, average number of tumors per tumor bearing mice and the cumulative number of papillomas was observed in mice treated topically with the leaf extract of O. sanctum at either the peri-initiational, post-initiational stages or continuously at peri- and post-initiational stages of papillomagenesis as compared to the corresponding control group. Topical application of Ocimum leaf extract for 15 days resulted in significant 2-fold elevation of reduced glutathione content in the skin of mice (p < 0.05). Similarly, glutathione S-transferase activity was also observed to be significantly elevated by 25% compared with the control group (p < 0.05) following Ocimum extract treatment.

9,10-Dimethyl-1,2-benzanthracene↗

Cerebrospinal fluid dopamine in HIV-1 infection.

BACKGROUND: Increasing evidence suggests significant involvement of the basal ganglia in patients with HIV-1 infection. OBJECTIVE: To study the effect of HIV-1 infection on cerebrospinal fluid (CSF) dopamine levels. DESIGN: CSF dopamine levels were measured by high-performance liquid chromatography. SETTING: A university-based outpatient clinic in south Florida involved in clinical AIDS research. SUBJECTS: Twenty-two subjects were enrolled in a prospective, longitudinal study of the neurological complications of AIDS. Five subjects were HIV-seronegative, but at risk for HIV-1 infection, 11 were HIV-1-seropositive without neurological disease and six had HIV-1-related neurological disease. RESULTS: The CSF dopamine mean values were significantly lower in the HIV-1-seropositive group with (P < 0.0001) or without (P < 0.0001) neurological disease than in the HIV-seronegative group. There was a very strong correlation between CD4 lymphocyte counts and CSF dopamine levels (P = 0.004) in the neurologically symptomatic group (P = 0.0008), but not in the other two groups. CONCLUSION: HIV-1 infection appears to have an effect on the central nervous system dopaminergic systems, as reflected in levels of CSF dopamine.

Adult↗

Massive upper gastrointestinal bleeding due to Candida esophagitis.

Significant hemorrhage from esophageal candidiasis in patients without a major bleeding diathesis is extremely uncommon. A case of recurrent, severe upper gastrointestinal bleeding due to hemorrhagic candidal esophagitis in a man with renal failure is described. Dysphagia, odynophagia, and retrosternal chest discomfort were all absent. Oral thrush was present only at the outset. Standard therapy for massive bleeding with blood products alone was not successful. Intravenous amphotericin eventually resulted in resolution.

Acute Kidney Injury↗

Brainstem auditory evoked response changes following electro-acupuncture therapy in chronic pain patients.

Brainstem auditory evoked responses were recorded in 17 patients with chronic pain who had been given electro-acupuncture therapy. The absolute peak latencies of waves I to V, and interpeak latencies and amplitudes of waves I and V were analysed before electro-acupuncture and compared with values obtained during electro-acupuncture and 5 min after its termination after one, five and 10 sittings. At these sittings the intensity of pain was recorded with the help of a 100 mm visual analogue scale. Each patient had 10 sittings given on alternate days. The absolute peak latencies of waves I, II, and III were delayed significantly (p < 0.05) after 5 and 10 sittings and amplitudes of wave V decreased significantly (p < 0.05) after 5 and 10 sittings. Visual analogue scores also decreased significantly (p < 0.01) during these sittings. It was established that before and after 10 sittings of electro-acupuncture, there was a significant positive correlation between visual analogue scores and the amplitude of wave V (p < 0.01). There was a negative correlation between visual analogue scores and absolute peak latencies of wave III at 1, 5 and 10 sittings, suggesting that there is a definite interaction between the electro-acupuncture neural mechanism and the generators of brainstem auditory evoked responses in the lower brainstem.

Adolescent↗