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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 109 records · Page 6Linked to original sources
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Recovery from pre-operative sedation with clonidine--brain stem auditory evoked response.

In a randomised double-blind study, 34 elderly patients (ASA grades 1-2) underwent elective intra-ocular surgery. Patients were allocated randomly to two groups to receive oral clonidine 300 micrograms or oral diazepam 10 mg 2 h before surgery. Facial block and retrobulbar block were given at 2 h after premedication. Anaesthetic recovery was assessed using a clinical recovery score (at 0, 30, 60 and 120 min after arrival in the recovery room) and brain stem auditory evoked potential responses (BAER) (immediately after operation and at 120 min after operation). In both the groups the clinical recovery scores decreased significantly at 30 and 60 min following recovery (p < 0.01). At 120 min this score returned to the pre-operative value in the clonidine group, but in the diazepam group there was a significant difference between the 2h value and pre-operative value (p < 0.05). In the clonidine group there was no significant rise in the interpeak latencies and absolute peak latencies of brain stem auditory evoked responses recorded immediately after operation and 120 min after operation. In the diazepam group, there was a significant rise in the interpeak latencies immediately after operation and 120 min after operation and a rise in absolute peak latencies (p < 0.05) immediately after operation. In the clonidine group there was a reduction (p < 0.05) in amplitude of wave V at immediately after operation. We conclude that clonidine 300 micrograms orally before surgery does not delay recovery.

Aged↗
PubMed1994

Multiple carpometacarpal dislocations.

We present a case of dislocations of the carpometacarpal joints without associated fractures. Although carpometacarpal injuries are relatively uncommon, it is rare for multiple carpometacarpal dislocations to occur without associated fractures. The injury is difficult to diagnose because of swelling of the hand. A lateral radiograph of the wrist has been found to be mandatory to its precise diagnosis if suspected. In the case presented here early diagnosis and closed manipulation in the accident and emergency (A&E) department resulted in a good outcome.

Adult↗
PubMed1994

Effects of TGF-beta and TNF-alpha on procoagulant and fibrinolytic pathways of human tracheal epithelial cells.

The epithelial lining of the airways is subject to injury through several processes, including infections, bronchiolitis, and fume exposures. Because airway fibrin deposition influences the course of local injury, we examined how two inflammatory cytokines influenced fibrin formation and clearance in human tracheal epithelial cells (TEC). TEC were treated with transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha). TNF-alpha increased release of tissue factor (TF)-related procoagulant activity that, through generation of factor Xa, promotes assembly of the prothrombinase complex at the cell surface. Fibrinolytic activity was plasminogen dependent and due to both urokinase (uPA) and tissue plasminogen activator (tPA). The cells expressed plasminogen activator inhibitor 1 (PAI-1), but relatively little PAI-2. Depression of fibrinolysis by TGF-beta correlated with increased PAI-1. Conversely, TNF-alpha increased plasminogen activator (PA) activity due to increased uPA. Fibrinolytic activity was inhibited by actinomycin D and cyclohexamide, but changes in mRNAs for uPA, tPA, PAI-1, and TF by either cytokine were not appreciable. PAI-2 mRNA was not found. The data indicate that TGF-beta decreases the fibrinolytic capacity of TEC, suggesting that this cytokine promotes fibrin retention. TNF-alpha increases expression of both procoagulant and fibrinolytic activities; this differential regulation could favor both pericellular fibrin formation and dissolution.

Base Sequence↗
PubMed1994

Topical atropine and timolol therapy in failed retinal detachment surgery.

We conducted a double-blind randomized prospective study to evaluate the efficacy of topical timolol alone and topical timolol and atropine combined in cases of operated failed retinal detachment surgery cases in which no apparent open break explained the surgical failure. In both groups with and without proliferative vitreoretinopathy no statistically significant difference in retinal reattachment was found.

Administration, Topical↗
PubMed1994

SLE in Indian men: analysis of the clinical and laboratory features with a review of the literature.

Data on the clinical and laboratory profile of 39 male lupus patients has been analysed. An attempt has been made to (1) delineate the pattern of SLE in Indian males, (2) compare it with that reported in the world literature, (3) find out differences, if any, between male children and adults with the disease, and (4) compare it with our previously published data on Indian females with SLE. Several important points were brought out in this study. First, SLE in Indian males has an earlier age of disease onset, a higher incidence of mucocutaneous and renal involvement and a lower incidence of neuropsychiatric, gastrointestinal and hematological disease in comparison to those published from the developed countries. Second, leucopenia and lymphopenia, a reflection of disease severity, occur significantly more in male children compared with adults. Thrombocytopenia is exclusively noted in adult males and virtually non-existent in children. Third, male patients overall have a less severe form of the disease in comparison with their female counterpart, as was evident by significantly less patients with hypocomplementemia, diffuse proliferative lupus nephritis and psychosis. Finally, a higher frequency of infection, particularly tuberculosis, was seen in male patients, which was the cause of death in some.

Adolescent↗
PubMed1994

Interleukin-1 regulates corticosterone secretion from the rat adrenal gland through a catecholamine-dependent and prostaglandin E2-independent mechanism.

Studies from this and other laboratories have shown that interleukin-1 alpha (IL-1 alpha) stimulates corticosterone and prostaglandin (PG) release from primary cultures of rat adrenal cells. A previous report from our laboratory (1) indicated involvement of the alpha-adrenergic system in IL-1 alpha-stimulated corticosterone secretion from primary cultures of rat adrenal cells. The present experiments were conducted to determine the role of catecholamines and eicosanoids in IL-1-stimulated corticosterone release from primary rat adrenal cells. Primary adrenal cells were incubated for 24 h at 37 C with IL-1 alpha (10 nM), medium, or the appropriate agonist. After incubation, the supernatant was removed and assayed for epinephrine, prostaglandin E2 (PGE2), and corticosterone concentrations. At this time, untreated adrenal cells were fixed for immunohistochemical staining with a specific antirat tyrosine hydroxylase antibody. The results indicate that the primary adrenal cells contained 3.1 +/- 0.45% tyrosine hydroxylase-positive cells. On the ultrastructural level, the chromaffin cells were found to be in direct cellular contact with cortical cells. IL-1 alpha significantly increased (P < 0.05) epinephrine, PGE2, and corticosterone levels above those in medium-treated controls from primary adrenal cells. In the presence of the alpha-adrenergic antagonist phentolamine (10 microM), IL-1 alpha-stimulated (P < 0.05) corticosterone release was inhibited, whereas IL-1 alpha-induced PGE2 release was not affected. Conversely, the presence of the cyclooxygenase inhibitor indomethacin (10 microM) significantly inhibited IL-1 alpha-induced PGE2 secretion without altering the effect of IL-1 alpha on corticosterone release. Inhibitors of the 5-lipoxygenase system (10 microM CGS 8518) and the lipoxygenase and cytochrome P450 monooxygenase systems (10 microM nordihydroguaiaretic acid) did not effect IL-1 alpha-induced corticosterone or PGE2 release. These observations indicate that IL-1 alpha stimulates corticosterone release through an alpha-adrenergic mechanism that is independent of PGE2 release from primary rat adrenal cells.

Adrenal Glands↗
PubMed1994

Differential growth factor-induced modulation of proteoglycans synthesized by normal human renal versus cyst-derived cells.

In polycystic kidney disease (PKD), there is an insiduous enlargement of the kidneys and dilation of the renal tubules associated with extracellular matrix (ECM) alterations. The latter include thickening of tubular basement membrane and decreased synthesis of sulfated proteoglycan (PG). Because PKD is believed to be a disorder of cell growth and deranged ECM metabolism, it is conceivable that the formation of cystic tubules may be modulated by certain growth factors (GF) that influence the synthesis of ECM glycoproteins. In this study, the effect of various GF, i.e., epidermal, hepatocyte (HGF) and transforming (TGF), and triiodothyronine on the PG synthesized by normal human kidney (NK) epithelial cells and cells derived from cysts of patients with autosomal dominant PKD (ADPKD) was assessed. (35S) sulfate incorporation studies revealed that, among various GF, HGF and TGF-beta 1 had the maximal stimulatory effect on the synthesis of PG extracted from ADPKD cells. A minimal increase in the PG synthesis was observed in NK cells; however, PG synthesized under the influence of HGF or TGF-beta 1 were of relatively higher molecular weight, with a shift of K(av) from 0.28 to 0.12, as ascertained by Sepharose-6B chromatography. PG synthesized by ADPKD cells had a K(av) = 0.18, and it did not change with the GF treatment. The charge-density characteristics of PG of ADPKD cells were relatively lower than those of NK cells, and they were unaffected by HGF or TGF-beta 1 treatment. Interestingly, both the HGF and TGF-beta 1 significantly affected posttranslational modifications of PG.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1994

A safe percutaneous procedure for trigger finger release.

A safe and easily performed method for percutaneous release of trigger digits is described which is performed in the outpatient clinic within a few minutes, without requiring any special instrument. Results in terms of abolishing triggering immediately and patient acceptance are excellent. No important complications have been observed in our first 38 procedures.

Ambulatory Surgical Procedures↗
PubMed1994

Malaria control utilizing Bacillus sphaericus against Anopheles stephensi in Panaji, Goa.

In a large malaria endemic area in Panaji city, Goa, India, the weekly application of the biolarvicide Bacillus sphaericus (Strain 101, Serotype H 5a 5b) at the rate of 1 g/m2 in the main Anopheles stephensi larval habitats, viz., curing waters, masonry tanks, and sump tanks (under construction), from April to December 1993 resulted in a sharp decline in the habitat positivity (range 0.13-8.0%) as compared with the rest of the Panaji (range 2.2-30.6%) where temephos (Abate) was used as the larvicide. Bacillus sphaericus spraying also led to a significant decline in anopheline densities in positive habitats (range 0-7.3/10 dips) as compared with control habitats (range 0.9-53.0/10 dips). Concurrently, malaria incidence observed in the experimental area (slide positivity rate [SPR] range 2.3-7.8%; monthly parasite index [MPI] range 0.18-1.44) was lower than in the control area (SPR range 14.3-25.5%; MPI range 1.75-6.12).

Animals↗