Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 415 records · Page 23Linked to original sources

PubMed1999

Recombinant soluble form of PSGL-1 accelerates thrombolysis and prevents reocclusion in a porcine model.

BACKGROUND: We investigated whether administration of a soluble recombinant P-selectin glycoprotein ligand-1 chimera (rPSGL-Ig) in conjunction with thrombolytic therapy would enhance thrombolysis by preventing ongoing interactions of leukocytes with platelets and the injured arterial wall. METHODS AND RESULTS: An occlusive thrombus was formed in an internal iliac artery of Yorkshire pigs by placement of a copper coil in the artery under fluoroscopic guidance. Pigs then received heparin and, 15 minutes later, either vehicle or rPSGL-Ig followed by infusion with 25 mg tissue plasminogen activator according to the 90-minute regimen. Blood flow through the artery was monitored by angiography and scored on a scale of 0 to 3. Lysis of the thrombus was accelerated by 70% in pigs treated with rPSGL-Ig 250 microg/kg compared with control (13.3+/-5.0 versus 44. 4+/-13.3 minutes; n=9 each). Eight of 9 control pigs reoccluded in 13.8+/-16.9 minutes after the end of tissue plasminogen activator infusion, whereas no reocclusion was observed in 8 of 9 pigs in the rPSGL-Ig group. When the dose of rPSGL-Ig was increased to 500 microg/kg, time to lysis was shortened by 61% from control (18.0+/-8. 4 versus 46.0+/-8.9 minutes). Reocclusion occurred in 6.0+/-15.2 minutes in control but not in any rPSGL-Ig-treated pig (n=5 each). In addition, near-normal flow (score 2 or 3) after thrombolysis was achieved 59% and 58% faster in the 2 rPSGL-Ig groups than in their respective controls. CONCLUSIONS: Inhibition of leukocyte accumulation at the site of thrombosis with rPSGL-Ig may represent a safe therapeutic intervention that could be important in accelerating thrombolysis, achieving optimal reperfusion, and reducing incidence of acute reocclusion.

Animals↗

PubMed1999

Orphan receptor Arp-1 binds to the nucleotide sequence located between TATA box and transcriptional initiation site of the human angiotensinogen gene and reduces estrogen induced promoter activity.

Human angiotensinogen gene contains a C/A polymorphism at 20 bases upstream from the transcriptional initiation site. This sequence binds to the estrogen receptor when nucleoside A is present at this site and reporter constructs containing human angiotensinogen gene promoter with nucleoside A at -20 are transactivated on co-transfection of estrogen receptor in HepG2 cells followed by estrogen treatment. We show here that orphan receptor, Arp-1, which belongs to the COUP family of transcription factors also binds to this sequence. Co-transfection of Arp-1 reduces estrogen induced promoter activity of reporter constructs containing human angiotensinogen gene promoter. On the other hand co-transfection of Arp-1 does not have a significant effect on estrogen induced promoter activity of reporter constructs containing rat angiotensinogen gene promoter. Our data suggests that human and rat angiotensinogen genes are regulated in a different manner by estrogens.

Angiotensinogen↗

PubMed1999

Outcome of twin pregnancy in a renal transplant recipient treated with tacrolimus.

Our report describes the outcome of a twin pregnancy in a woman who was maintained on tacrolimus after a living related renal transplant. Both babies born at 32 weeks of gestation developed severe respiratory distress requiring ventilator assistance and went on to develop congestive heart failure. Echocardiograms on both babies showed dilated heart chambers. Twin A succumbed to complications, but twin B, who was treated more aggressively with vasopressors, recovered. Autopsy findings on twin A revealed a thrombotic cardiomyopathy with degeneration of cardiac muscle. We believe that the unusual outcome in this set of twins may have been a result of cardiomyopathy secondary to tacrolimus used by the mother during her pregnancy.

Azathioprine↗

PubMed1999

Modulatory potential of Spirulina fusiformis on carcinogen metabolizing enzymes in Swiss albino mice.

The modulatory potential of Spirulina fusiformis was observed on the hepatic and extrahepatic carcinogen metabolizing enzymes in Swiss albino mice at a dose of 800 mg/kg b.w. given orally. A significant reduction in the hepatic cytochrome P-450 content was observed in the group treated with Spirulina in comparison with the control group. The hepatic glutathione S-transferase activity was induced significantly by Spirulina treatment. There was no change in the extrahepatic glutathione S-transferase activity after the animals were fed with Spirulina.

Animals↗

PubMed1999

Modulation of lead toxicity by Spirulina fusiformis.

The modulatory effects of lead toxicity by Spirulina fusiformis (Oscillatoreaceae) were observed on the testes of Swiss albino mice at a dose of 800 mg/kg body weight. The Spirulina fusiformis was non-toxic at the dose given. A significant enhancement in the survival time was observed in the pre- and post-treated Spirulina group compared with the control (lead treated) group. Lead induced toxicity was also reduced in terms of testes weight, animal weight, tubular diameter in the pre Spirulina treated group. The modulatory effects of Spirulina may be attributed to the presence of the antioxidants, beta-carotene and SOD enzyme.

Animals↗

PubMed1999

Chemopreventive action by an extract from Brassica compestris (var Sarason) on 7,12-dimethylbenz(a)anthracene induced skin papillomagenesis in mice.

We report the chemopreventive property of an ethanolic extract of the seeds of Brassica compestris var sarason (mustard seed) on DMBA (7,12 dimethylbenz(a)anthracene induced skin papillomagenesis in male Swiss albino mice. A significant reduction in the values of tumour incidence, tumour burden and the cumulative number of papillomas was observed in mice treated orally with the seed extract of Brassica compestris var sarason, continuously at peri and post initiational stages of papillomagenesis compared with the control groups. The latency period in the experimental group significantly increased (11.3 +/- 0.40 weeks) compared with the control group (7.8 +/- 0.17).

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

Stereoselective urinary excretion of bupivacaine and its metabolites during epidural infusion.

A sensitive and efficient chiral assay for bupivacaine and its three principal metabolites desbutylbupivacaine, 4'-hydroxybupivacaine, and 3'-hydroxybupivacaine has been applied to urine from five male patients receiving postoperative epidural infusions of rac-bupivacaine fentanyl over 60-120 hr. The fraction of the dose of bupivacaine (total dose 840-2093 mg) accounted for in urine was 75 +/- 6%. The rate of excretion of bupivacaine enantiomers' approximated a steady state after approximately 30 hr with values of 1.27 +/- 0.26 and 0.76 +/- 0.13 mg hr-1 for (R)- and (S)-enantiomers, respectively. The fraction of the dose of bupivacaine enantiomer excreted unchanged in the urine (fe) varied from 14.3% to 39.1% for (+)-(R)-bupivacaine and 9.2% to 14.0% for (-)-(S)-bupivacaine in the five patients. The rate of excretion of all metabolites also reached a steady state after approximately 30 hr and the relative amounts of metabolites excreted into urine (fm) suggest bupivacaine is subject to regioselective and stereoselective clearance, which may vary from patient to patient.

Aged↗

PubMed1999

The canals of Hering and hepatic stem cells in humans.

Small, extraportal, hepatic parenchymal cells, positive for biliary-type cytokeratins, may represent hepatic stem cells, canals of Hering (CoH), and/or ductal plate remnants. We evaluated these cells 3 dimensionally in normal human liver and massive necrosis. Tissues from normal human livers and from 1 liver with acetaminophen-induced massive necrosis were serially sectioned, immunostained for cytokeratin 19 (CK19), and sequentially photographed. Images were examined to determine 3-dimensional relationships among CK19-positive cells. Immunostains for other hepatocyte and progenitor cell markers were examined. In normal livers, intraparenchymal CK19-positive cells lined up as linear arrays in sequential levels. One hundred of 106 (94.3%) defined, complete arrays within levels examined, most having 1 terminus at a bile duct, the other in the lobule, beyond the limiting plate. In massive necrosis, there were 767 individual CK19-positive cells or clusters around a single portal tract, 747 (97.4%) of which were spatially related forming arborizing networks connected to the interlobular bile duct by single tributaries. C-kit was positive in normal CoH. CK19 co-expressed with HepPar1, c-kit, and alpha-fetoprotein (AFP) in parenchymal cells in massive necrosis. Small, extraportal, biliary-type parenchymal cells represent cross-sections of the CoH that radiate from the portal tract, usually extending past the limiting plate into the proximate third of the hepatic lobule. The 3-dimensional structure of ductular reactions in massive necrosis suggests that these reactions are proliferations of the cells lining the CoH. Therefore, the CoH consist of, or harbor, facultative hepatic stem cells in humans.

Acetaminophen↗

PubMed1999

Plasmodium falciparum: drug-resistant malaria complicating leukemias and lymphomas in children.

The present communication deals with drug-resistant Plasmodium falciparum malaria complicating hematologic malignancies (leukemias, n = 24, and lymphomas, n = 7) in children. Of 50 cases of hematologic malignancies, 31 patients were microscopically diagnosed as having P. falciparum infection (MP +). Initially, all the patients were treated with chloroquine. The results of primary treatment showed chloroquine resistance in 16 (51. 62%) cases. Of these 16 chloroquine-resistant cases, 13 were secondarily treated with a combination of pyrimethamine plus sulfamethopyrazine. The results of secondary treatment also revealed resistance to pyrimethamine plus sulfamethopyrazine in 6 of 13 (46. 10%) cases. The 6 pyrimethamine plus sulfamethopyrazine-resistant P. falciparum cases were finally cured by quinine therapy, against which no resistance was encountered. Conversely, in the control group comprising 38 cases of P. falciparum without malignancy, the incidence of chloroquine resistance was found in only 9 cases, which is rather low (23.70%). Of these 7 chloroquine-resistant cases, 5 were found to be sensitive to pyrimethamine plus sulfamethopyrazine treatment, while the 2 nonresponders were finally cured with quinine. The overall results of this study show a high prevalence of chloroquine resistance among clinical cases of falciparum malaria (25/69; 30.6%). Among the nonresponders (n = 20) 40% of cases were also resistant to the pyrimethamine plus sulfamethopyrazine combination. There was no resistance to quinine.

Adolescent↗

PubMed1999

Large-scale propagation of recombinant adherent cells that secrete a stable form of human glandular kallikrein, hK2.

Human glandular kallikrein 2 (hK2) is a trypsin-like serine protease that is expressed predominantly in the prostate epithelium and has 78% aa identity with prostate-specific antigen (PSA). hK2 has been recognized as a potential prostate cancer marker and has been demonstrated to be highly expressed in prostate cancer compared to benign prostatic tissue. Purification and characterization of hK2 have been impeded due to its lower expression in bodily fluids and tissues compared to PSA and its ability to autodegrade. Therefore, to study biochemical and biological characteristics of hK2, a stable and enzymatically inactive mutant form of hK2, hK2(A217V), was expressed in a hamster cell line, AV12-664 (AV12-hK2(A217V)). AV12-hK2(A217V) cells secreted prohK2(A217V) (phK2(A217V)) in the spent medium at approximately 2.5 microgram/ml. Since AV12-hK2(A217V) are adherent cells, it was necessary to develop an efficient system to propagate large numbers of cells to obtain significant quantities of phK2(A217V). In this paper, we compared ceramic core bioreactor and microcarrier beads as alternatives to static culture to propagate adherent cells. Considering production levels, ease of operation, cost effectiveness, and labor, microcarrier beads were found to be a better alternative. Our findings led to the development of a general protocol for large-scale propagation of adherent cells on microcarrier beads eliminating the need for propagating AV12-hK2(A217V) in culture flasks or bioreactors. Microcarrier beads coated with AV12-hK2(A217V) cells could be propagated in 1- or 3-liter spinner flasks and were passed from one spinner to the next in a manner analogous to static culture or could be frozen and later used as inoculum for subsequent spinners. Using this protocol, >40 liters of spent medium was harvested within 30 days, which in turn was used to purify phK2(A217V). phK2(A217V) purified from spent medium of cells grown either on microcarrier beads or in culture flasks were biochemically similar as indicated by HIC-HPLC profile followed by sequencing of relevant peaks.

Animals↗

PubMed1999

Phylogeny and transpositional activity of Ty1-copia group retrotransposons in cereal genomes.

The Ty1-copia group retrotransposon populations of barley (Hordeum vulgare) and bread wheat (Triticum aestivum) have been characterised by degenerate PCR and sequence analysis of fragments of the reverse transcriptase genes. The barley population is comprised of a highly heterogeneous set of retrotransposons, together with a collection of sequences that are closely related to the BARE-1 element. Wheat also contains a highly diverse Ty1-copia retrotransposon population, together with a less prominent BARE-1 subgroup. These data have been combined with previously published Gramineae sequences to construct a composite phylogenetic tree for this class of retrotransposons in cereal grasses. The analysis indicates that the ancestral Gramineae genome contained a heterogeneous population of Ty1-copia group retrotransposons, the descendants of which have proliferated to differing degrees in present-day species. Lastly, the level of recent transpositional activity of two Ty1-copia elements has been estimated by measuring their insertional polymorphism within species. Both transposons are highly polymorphic within all species tested. These data suggest that transposition proficiency may be a common and evolutionarily stable feature of the Ty1-copia group retrotransposons of cereal grasses.

Base Sequence↗

PubMed1999

Adenocarcinoma of distal esophagus and gastroesophageal junction: long-term results of surgical treatment in a North Indian Center.

This retrospective study reports our experience managing 78 patients with adenocarcinoma of the esophagus and gastroesophageal junction operated between January 1982 and December 1996. Altogether 18 patients presented with stage I and II disease, and 60 patients had stage III and IV disease at presentation; 56 patients (71.8%) were found to have resectable disease. Of these, transhiatal esophagectomy was possible in 51 patients. Transthoracic esophagectomy was done in 3 patients, and a left thoracoabdominal approach was used in 2 patients. The stomach was used as conduit in 50 patients and the colon in 6 patients. Twenty-two patients were found to have unresectable lesions at laparotomy and underwent various palliative procedures. Overall operative mortality was 6.3%. Mortality in the resectable group was only 3.6%. Follow-up ranges from 3 to 128 months, with four patients lost to follow-up at 1, 6, 8, and 10 months. The 5-year survival of the whole group according to Kaplan and Meier survival analysis was 21.27% with a median survival of 13.48 months. Univariate analysis using the log-rank test revealed stage of the disease and resectability to be significant predictors of survival. On multivariate analysis, curative resection appeared to be the most significant predictor of survival in patients undergoing resection.

Adenocarcinoma↗

PubMed1999

Congenital pouch colon in females.

From January 1995 to March 1998, congenital pouch colon (CPC) with anorectal agenesis was diagnosed in ten girls who were classified into four groups based on the length of normal colon proximal to the colonic pouch. Of six girls with little or no normal colon, one had a cloacal anomaly while five had a colovesical or colovestibular fistula along with a completely bifid uterus and cervix and a septate vagina. Initial surgery consisted of ligation of the fistula and subtotal pouch excision with tubularization of the remaining colon in four girls, ileostomy after excision of a gangrenous pouch in one, and window colostomy in another. None of the patients had a sacral abnormality or associated major malformation. Definitive surgery using the posterior sagittal approach consisted of a pull-through of the tubularized colon in three girls (including one in whom one-stage cloacal reconstruction was performed), the ileum in one, and the proximal colon in another. The four girls with a longer length of normal colon had an associated vestibular fistula. In these, a colostomy was constructed just proximal to the pouch with definitive surgery in two patients consisting of excision of the pouch and pull-through of the proximal colon. Definitive surgery was well tolerated in all seven patients. The embryogenesis of this condition and the related genitourinary tract abnormalities are discussed.

Abnormalities, Multiple↗

PubMed1999

Inferior vesical fistula.

Exstrophy variants are uncommon developmental anomalies of the bladder; the variants involving only the bladder neck are extremely rare. There are only two case reports of inferior vesical fissure to date, and inferior vesical fistula (IVF) as an exstrophy variant has not been described previously. We report a case of IVF in a 20-month-old female. The urethra was normal in calibre and position and the bladder capacity was adequate. Simple closure of the fistula was followed by a normal micturition pattern.

Bladder Exstrophy↗

PubMed1999

The neuropsychiatry of subcortical ischemic brain disease.

The subcortical regions of the brain, by virtue of their extensive connections to neocortical and limbic structures, play an important role in the regulation of neurobehavioral functions such as mood, memory, and affect. Compromise of the blood supply to the subcortex and its connections result in behavioral syndromes that often include disturbances in cognition and mood. The extent of the underlying vascular pathology and the precise circuits compromised, in general, determine the nature of the behavioral problems. The neurobiologic mechanisms responsible for these behaviors are complex and clinical management is symptomatic and largely aimed at treating the primary clinical features with appropriate pharmacologic and behavioral approaches.

Behavior Therapy↗

PubMed1999

Somatic mutations of the L12a gene in V-kappa(1) light chain deposition disease: potential effects on aberrant protein conformation and deposition.

Light chain deposition disease (LCDD) and light chain amyloidosis (AL) are disorders of monoclonal immunoglobulin deposition in which normally soluble serum precursors form insoluble deposits in tissues. A common feature in both is the clonal proliferation of B-cells that produce pathogenic light chains. However, the deposits in LCDD differ from those in AL in that they are ultrastructurally granular rather than fibrillar and do not bind Congo red or colocalize with amyloid P component or apolipoprotein E. The reason(s) for their differences are unknown but are likely multifactorial and related to their protein conformation and their interaction with other molecules and tissue factors in the microenvironment. Knowledge of the primary structure of the light chains in LCDD is very limited. In the present study two new kappa(1) light chains from patients with LCDD are described and compared to seven other reported kappa-LCDD proteins. The N-terminal amino acid sequences of light chain GLA extracted from the renal biopsy and light chain CHO from myocardial tissue were each identical to the respective light chains isolated from the urines and to the V-region amino acid sequences translated from the cloned cDNAs obtained from bone marrow cells. The germline V-region sequences, determined from the genomic DNA in both and in MCM, a previously reported kappa(1) LCDD light chain, were identical and related to the L12a germline gene. The expressed light chains in all three exhibit amino acid substitutions that arise from somatic mutation and result in increased hydrophobicity with the potential for protein destabilization and disordered conformation.

Amino Acid Sequence↗

PubMed1999

Ultrasound guided aspiration of endometrioma--a new therapeutic modality to improve reproductive outcome.

OBJECTIVE: To evaluate the therapeutic efficacy and reproductive outcome following ultrasound guided aspiration (UGA) of endometrioma in infertile patients. METHOD: This is a prospective non-randomized clinical report of UGA in 22 infertile patients with endometrioma. The aspiration of endometriotic cysts was carried out transvaginally in nine and transabdominally in 13 patients. Following aspiration intranasal buserilin was given to eight and danazol to 14 patients. In the case of recurrence a reaspiration was done. Patients were allowed to conceive following medical therapy. Recurrence of endometrioma and conception rate was recorded and correlated with endometrioma size and volume aspirated. RESULT: A total of 47 aspirations were done. There were no procedure related complications. Reaspiration was required in six patients and one was operated (total recurrence 7/22--31.8%). During a mean follow-up of 20+/-8.4 months nine patients (40.9%) conceived and eight have already delivered at term. The recurrence risk and the conception rate was not affected by the cyst size or volume aspirated. CONCLUSION: UGA of endometrioma can be an effective and safe alternative therapeutic procedure in infertile patients with endometrioma to improve their reproductive outcome.

Adult↗

PubMed1999

Management of functional bladder neck obstruction in women: use of alpha-blockers and pediatric resectoscope for bladder neck incision.

PURPOSE: Functional bladder neck obstruction has been definitively diagnosed in the last few years due to detailed synchronous pressure flow, electromyography and video urodynamics. Clean intermittent self-catheterization and bladder neck incision are the modalities of treatment. To our knowledge the role of alpha-blockers is not yet defined in women. A new technique was developed to perform bladder neck incision using a pediatric resectoscope. MATERIALS AND METHODS: A total of 24 women with obstructive voiding symptoms or retention were evaluated with video pressure flow electromyography, and diagnosed with functional bladder neck obstruction due to high pressure and low flow on silent electromyography and bladder neck appearance on fluoroscopy. Patients were initially treated with clean intermittent self-catheterization and alpha-blockers. Catheterization was stopped when post-void residual was less than 50 ml. and only alpha-blocker therapy was continued. Bladder neck incision was performed in patients who had a poor response to or side effects of alpha-blocker therapy, or when therapy was discontinued due to economic reasons. Clean intermittent self-catheterization was continued in patients who had a poor response to alpha-blockers or refused to undergo bladder neck incision. Bladder neck incision was performed in the initial 2 cases with an adult resectoscope using a Collin's knife and subsequently a pediatric resectoscope (13F). Uroflow and post-void residual measurements were performed in all cases. RESULTS: Of the 24 patients 12 (50%) showed improvement in symptoms, peak flow and post-void residual (p <0.01) with alpha-blocker therapy only. Of the 12 patients who had a poor response to alpha-blockers 6 underwent bladder neck incision subsequently and 6 remained on clean intermittent self-catheterization. All 8 patients treated with bladder neck incision, including 2 who had a good response but discontinued alpha-blocker therapy, had sustained improvement in post-void residual and peak flow (p <0.01) after a mean followup of 3.8 +/- 2.4 years. Grade 1 stress incontinence in 2 adult resectoscope cases responded to conservative treatment. None of the pediatric resectoscope cases had stress incontinence. CONCLUSIONS: Clean intermittent self-catheterization and alpha-blockers are the initial treatment options for functional bladder neck obstruction. The alpha-blockers were successful in 50% of our patients. Bladder neck incision should be offered judiciously with minimal risk of curable stress incontinence. The pediatric resectoscope is useful to make a well controlled incision safely in the female urethra.

Adrenergic alpha-Antagonists↗