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Biomedical subjects

S Kaul

Publications and source records attributed to S Kaul.

At least 109 records · Page 6Linked to original sources
PubMed2000

Sensitive and specific detection of carcinoembryonic antigen cDNA using the hot start polymerase chain reaction technique.

This study evaluated the specificity and sensitivity of hot start polymerase chain reaction (RT-PCR) for identification of carcinoembryonic antigen (CEA) cDNA. Hot Start Storage and Reaction Tubes provide a simple mechanism for synchronizing hot start amplifications without the need for manual intervention. A wax barrier uses a layer of solid wax to separate the retained reagents and the test sample from the bulk of the reagents until the first heating step of automated thermal cycling melts the wax and convectively mixes the two aqueous layers. Wax-mediated hot start PCR greatly increases the specificity and sensitivity of amplifying CEA cDNA. 12 out of 12 samples were positive for CEA cDNA from 10 CEA mRNA positive tumor cells in 10(7) normal cells by hot start CEA-PCR, and 8 out of these samples were positive for CEA cDNA by CEA-PCR without hot start. The hot start PCR showed the single specific product band, but PCR without hot start showed the specific product band and the other non-specific product band. We conclude that the hot start PCR technique could sensitively and specifically detect CEA cDNA after reverse transcription of CEA mRNA and minimize primer dimers by amplification.

Breast Neoplasms↗
PubMed2000

Frequency, clinical features and risk factors of lacunar infarction (data from a stroke registry in South India).

Analysis of 893 patients of ischaemic stroke in the stroke registry of Nizam's institute of Medical Sciences, Hyderabad is presented. 16% of them had lacunar infarction. The mean age at presentation was 56.9 years and male to female ratio was 3.5:1. The common risk factors included hypertension(62%),diabetes(38%) and smoking(28%). Six percent had an underlying cardiac source of embolism and none had significant (>50%) extracranial carotid atherosclerosis. In 22% of patients, no obvious risk factors could be identified. The frequency of risk factors was similar in patients with lacunar and non- lacunar infarctions. However, patients with lacunar infarction had higher frequency of diabetes and absence of significant (>50%) extracranial carotid artery disease. Pure motor hemiparesis was the presenting syndrome in 45% patients. Ataxic hemiparesis and sensorimotor stroke accounted for 18% each and dysarthria-clumsy hand syndrome for 14%. This study suggests that the frequency, risk factors and clinical profile of lacunar infarction in our stroke registry is similar to most of the western stroke registries.

Aged↗
PubMed2000

Spinal extradural abscess following local steroid injection.

A case of spinal extradural abscess following local steroid injection for back ache, in a 26 years old male is described. The abscess presented as a swelling externally. MRI localised the lesion to L2-S1 segments. Mechanism of such an infection has been discussed.

Abscess↗
PubMed2000

Clinical features of cardioembolic strokes identified by transesophageal echocardiography.

Clinical and CT scan features predictive of a cardiac source of embolism (CSOE) are helpful in planning appropriate investigations in ischaemic strokes. The currently described predictors of CSOE were determined before the availability of trans esophageal echocardiography (TEE). After the advent of TEE, many new CSOE were discovered. The present study was planned to investigate if the previously described predictors of CSOE are also valid for patients with CSOE detectable only with TEE (TEE-detected CSOE). From 1992-1995, 485 consecutive patients of ischemic stroke were enrolled in the Maryland Stroke Data Bank (MSDB). Patients with CSOE identified only by TEE and not by clinical, electrocardiographic or transthoracic echocardiographic (TTE) examination were compared to patients with a CSOE with respect to the features of the history, neurologic examination and CT scan. Of 485 patients with cerebral infarction, 132 (27%) patients had CSOE. In 21/132 (16%), diagnosis of high risk CSOE could be established only by TEE. The most discriminating clinical findings in TEE-detected CSOE patients were visual field deficit (OR 2.9; 95% CI, 1.1-7.4) and neglect (OR 3.4; 95% CI,1.2-9.3). Less strong associations were also found with other clinical features described previously for CSOE. No significant differences were found for features of the initial CT scan. In summary, presence of visual field defect and hemineglect may suggest a higher likelihood of finding a CSOE by TEE, even if the clinical cardiac examination and TTE are normal.

Adult↗
PubMed2000

Primary fibrosarcoma of brain.

This is a case presentation of a young patient with an intracranial space-occupying lesion following multiple episodes of generalised tonic clonic seizures for the last 20 years. Such a long latency period between the onset of fits and the discovery of an intracranial lesion is highly unusual in malignant brain tumours. This lesion was excised completely and proved to be a primary lesion of the brain - fibrosarcoma. These rare tumours of mesenchymal origin in the central nervous system are very rare.

Adult↗
PubMed2000

Patient satisfaction with pre-operative analgesia in acute trauma.

We performed a prospective study of 100 consecutive patients admitted to the Orthopaedic and Trauma Unit at the North Staffordshire Royal Infirmary following acute injury. We assessed the patient's level of pain and perception of pain relief in the period from their admission to hospital and surgery, or the first 24 hours as an inpatient using a questionnaire. We found that 54% of patients described their pain as 'severe' or 'the worst possible pain'. Significantly, 36% of patients would have liked more analgesia. We conclude that patients are not receiving the analgesia they require following acute injury.

Adult↗
PubMed2000

Beneficial antithrombotic effects of the association of pharmacological oral magnesium therapy with aspirin in coronary heart disease patients.

The use of magnesium in the treatment of acute myocardial infarction remains controversial despite preliminary experimental evidence that magnesium plays a beneficial role as a regulator of thrombosis. The aim of our study was to determine whether oral magnesium treatment inhibits platelet-dependent thrombosis (PDT) in stable patients with coronary artery disease (CAD). In a randomized prospective, double-blind, cross-over and placebo controlled study, 42 patients with stable CAD (37 men, 5 women, mean age 68 +/- 9 years) on aspirin received either magnesium oxide tablets (800-1,200 mg/day) or placebo for 3 months (Phase 1) followed by a 4-week washout period, and the cross-over treatment for 3 months (Phase 2). PDT, platelet aggregation, platelet P-selectin flow-cytometry, monocyte tissue factor procoagulant activity (TF-PCA) and adhesion molecules density were assessed before and after each phase. PDT was evaluated by an ex-vivo perfusion model using the Badimon chamber. Median PDT was significantly reduced by 35 percent in patients who received magnesium versus placebo (D change from baseline: -24 vs. 26 microm2/mm; p = 0.02, respectively). There was no significant effect of magnesium treatment on platelet aggregation, P-selectin expression, monocyte TF-PCA or adhesion molecules. Oral magnesium treatment inhibits PDT in patients with stable CAD. This effect appears to be independent of platelet aggregation or P-selectin expression, and is evident despite aspirin therapy. These findings suggest a potential mechanism whereby magnesium may beneficially alter outcomes in patients with CAD.

Administration, Oral↗
PubMed1999

Genetic definition and sequence analysis of Arabidopsis centromeres.

High-precision genetic mapping was used to define the regions that contain centromere functions on each natural chromosome in Arabidopsis thaliana. These regions exhibited dramatic recombinational repression and contained complex DNA surrounding large arrays of 180-base pair repeats. Unexpectedly, the DNA within the centromeres was not merely structural but also encoded several expressed genes. The regions flanking the centromeres were densely populated by repetitive elements yet experienced normal levels of recombination. The genetically defined centromeres were well conserved among Arabidopsis ecotypes but displayed limited sequence homology between different chromosomes, excluding repetitive DNA. This investigation provides a platform for dissecting the role of individual sequences in centromeres in higher eukaryotes.

Arabidopsis↗
PubMed1999

Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana.

Arabidopsis thaliana (Arabidopsis) is unique among plant model organisms in having a small genome (130-140 Mb), excellent physical and genetic maps, and little repetitive DNA. Here we report the sequence of chromosome 2 from the Columbia ecotype in two gap-free assemblies (contigs) of 3.6 and 16 megabases (Mb). The latter represents the longest published stretch of uninterrupted DNA sequence assembled from any organism to date. Chromosome 2 represents 15% of the genome and encodes 4,037 genes, 49% of which have no predicted function. Roughly 250 tandem gene duplications were found in addition to large-scale duplications of about 0.5 and 4.5 Mb between chromosomes 2 and 1 and between chromosomes 2 and 4, respectively. Sequencing of nearly 2 Mb within the genetically defined centromere revealed a low density of recognizable genes, and a high density and diverse range of vestigial and presumably inactive mobile elements. More unexpected is what appears to be a recent insertion of a continuous stretch of 75% of the mitochondrial genome into chromosome 2.

Arabidopsis↗
PubMed1999

Evidence that high-density lipoprotein cholesterol is an independent predictor of acute platelet-dependent thrombus formation.

Plasma total and low-density lipoprotein (LDL) cholesterol are established risk factors for atherosclerotic vascular disease and may also contribute to a prothrombotic risk via enhanced platelet reactivity. This study examines whether high-density lipoprotein (HDL) cholesterol, which is inversely correlated with coronary artery disease, is associated with a reduced thrombogenic potential. Platelet thrombus formation was evaluated by exposing porcine aortic media placed in Badimon perfusion chambers to flowing nonanticoagulated venous blood for 5 minutes at a shear rate of 1,000 s(-1). Forty-five subjects, 23 normal (LDL 104 +/- 31, HDL 50 +/- 15 mg/dl) and 22 hypercholesterolemic (LDL 181 +/- 45, HDL 41 +/- 10 mg/dl) patients without coronary artery disease were studied. Platelet aggregation and CD62 antigen expression, and assay for circulating prothrombotic factors were also performed. In univariate analysis platelet thrombus formation correlated with weight (r = 0.33, p = 0.03), diastolic blood pressure (r = 0.39, p = 0.01), HDL cholesterol (r = -0.45, p = 0.003), total/HDL cholesterol (r = 0.43, p = 0.004) and LDL/HDL (r = 0.38, p = 0.01) ratios, and platelet CD62 expression (r = 0.41, p = 0.02). In multiple regression analysis only HDL cholesterol showed significant correlation with platelet thrombus formation (p = 0.03). Platelet aggregation and circulating prothrombotic factors did not correlate with platelet thrombus formation. A comparison between normal and hypercholesterolemic subjects revealed enhanced thrombus area (0.026 +/- 0.20 vs 0.045 +/- 0.039 mm2/mm; p = 0.04), resting CD62 expression (6 +/- 7% vs 15 +/- 10% positive platelets, p = 0.02), and platelet aggregation (16.7 +/- 5.2 vs 21.7 +/- 6.7 ohms, p = 0.04) in hypercholesterolemic subjects. Our results demonstrate that HDL cholesterol is a significant independent predictor of ex vivo platelet thrombus formation.

Adult↗
PubMed1999

Oral magnesium supplementation inhibits platelet-dependent thrombosis in patients with coronary artery disease.

The use of magnesium in the treatment of acute myocardial infarction remains controversial despite preliminary experimental evidence that magnesium plays a beneficial role as a regulator of thrombosis. This study examines whether oral magnesium treatment inhibits platelet-dependent thrombosis (PDT) in patients with coronary artery disease (CAD). In a randomized prospective, double-blind, crossover, and placebo-controlled study, 42 patients with CAD (37 men, 5 women, mean age 68 +/- 9 years) on aspirin received either magnesium oxide tablets (800 to 1,200 mg/day) or placebo for 3 months (phase 1) followed by a 4-week wash-out period, and the crossover treatment for 3 months (phase 2). PDT, platelet aggregation, platelet P-selectin flow cytometry, monocyte tissue factor procoagulant activity (TF-PCA), and adhesion molecule density were assessed before and after each phase. PDT was evaluated by an ex vivo perfusion model using the Badimon chamber. Median PDT was significantly reduced by 35% in patients who received magnesium versus placebo (delta change from baseline -24 vs 26 mm2/mm; p = 0.02, respectively). There was no significant effect of magnesium treatment on platelet aggregation, P-selectin expression, monocyte TF-PCA, or adhesion molecules. Oral magnesium treatment inhibited PDT in patients with stable CAD. This effect appears to be independent of platelet aggregation or P-selectin expression, and is evident despite aspirin therapy. These findings suggest a potential mechanism whereby magnesium may beneficially alter outcomes in patients with CAD.

Aged↗
PubMed1999

Membrane type 1 matrix metalloproteinase expression in human atherosclerotic plaques: evidence for activation by proinflammatory mediators.

BACKGROUND: Matrix metalloproteinases (MMPs) are expressed in atherosclerotic plaques, where in their active form, they may contribute to vascular remodeling and plaque disruption. In this study, we tested the hypothesis that membrane type 1 MMP (MT1-MMP), a novel transmembrane MMP that activates pro-MMP-2 (gelatinase A), is expressed in human atherosclerotic plaques and that its expression is regulated by proinflammatory molecules. METHODS AND RESULTS: MT1-MMP expression was examined in normal and atherosclerotic human arteries by immunocytochemistry with specific antibodies. MT1-MMP expression in human saphenous vein-derived smooth muscle cells (SMCs) maintained in tissue culture was determined under basal conditions and in response to proinflammatory molecules (interleukin [IL]-1alpha, tumor necrosis factor [TNF]-alpha, and oxidized LDL [ox-LDL]) by use of Northern blot and ribonuclease protection assays for mRNA, Western blot and immunoprecipitation for protein, and gelatin zymography for catalytic activity. Medial SMCs of normal vessel wall expressed MT1-MMP. In atherosclerotic arteries, MT1-MMP expression was noted within the complex atheroma colocalizing with SMCs and macrophages (Mphi). Cultured SMCs constitutively expressed MT1-MMP mRNA and protein, which increased 2- to 4-fold over control in a time-dependent manner within 4 to 8 hours of exposure to IL-1alpha, TNF-alpha, and ox-LDL (thiobarbituric acid-reactive substances, 13.4 nmol/mg LDL protein), whereas native LDL had no effect. Flow cytometry revealed MT1-MMP expression by human monocyte-derived Mphi, which increased 3.8-fold over baseline within 6 hours after exposure to 10 ng/mL TNF-alpha. CONCLUSIONS: This study demonstrates that MT1-MMP, an activator of pro-MMP-2, is expressed by SMCs and Mphi in human atherosclerotic plaques. Furthermore, proinflammatory molecules upregulate MT1-MMP expression in vascular SMCs and Mphi. Thus, activation of SMCs and Mphi by proinflammatory molecules may influence extracellular matrix remodeling in atherosclerosis by regulating MT1-MMP expression.

Antibodies, Monoclonal↗
PubMed1999

Tenascin-C is expressed in macrophage-rich human coronary atherosclerotic plaque.

BACKGROUND: Tenascin is a large extracellular matrix glycoprotein generally found in adult tissues undergoing active remodeling such as healing wounds and tumors. To determine the potential role of tenascin-C (TN-C) in the pathophysiology of atherosclerosis, we investigated the pattern of expression of TN-C in human coronary atherosclerotic plaques. METHODS AND RESULTS: Immunohistochemical staining and in situ hybridization demonstrated minimal and random expression of TN-C in fibrotic but lipid-poor atherosclerotic plaques. In contrast, all plaques with an organized lipid core or ruptured intimal surface strongly expressed TN-C, which was preferentially concentrated around the lipid core, shoulder regions, and ruptured area of the plaques but not in the fibrous cap. TN-C was not detected in normal arterial tissue. To identify the cellular source of TN-C, the plaques were stained with smooth muscle cell- and macrophage-specific antibodies. TN-C expression correlated with the infiltration of macrophages. Northern blot and immunoprecipitation analysis showed that macrophages expressed 7. 0-kb TN-C mRNA and 220-kDa protein. Reverse transcription-polymerase chain reaction of total RNA derived from macrophages showed that they express the small isoform of TN-C. Zymogram analysis revealed that macrophages markedly increased MMP-9 expression. CONCLUSIONS: This study demonstrates that the level of TN-C expression correlates with the degree of inflammation present, not with plaque size. In addition, cultured macrophages have the capacity to express the TN-C gene. These findings suggest the significance of macrophages in the remodeling of atherosclerotic plaque matrix composition.

Adult↗
PubMed1999

Oxidized low-density lipoprotein regulates matrix metalloproteinase-9 and its tissue inhibitor in human monocyte-derived macrophages.

BACKGROUND: Macrophages in human atherosclerotic plaques produce a family of matrix metalloproteinases (MMPs), which may influence vascular remodeling and plaque disruption. Because oxidized LDL (ox-LDL) is implicated in many proatherogenic events, we hypothesized that ox-LDL would regulate expression of MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in monocyte-derived macrophages. MWRHOSA AND RESULTS: Mononuclear cells were isolated from normal human subjects with Ficoll-Paque density gradient centrifugation, and adherent cells were allowed to differentiate into macrophages during 7 days of culture in plastic dishes. On day 7, by use of serum-free medium, the macrophages were incubated with various concentrations of native LDL (n-LDL) and copper-oxidized LDL. Exposure to ox-LDL (10 to 50 microg/mL) increased MMP-9 mRNA expression as analyzed by Northern blot, protein expression as measured by ELISA and Western blot, and gelatinolytic activity as determined by zymography. The increase in MMP-9 expression was associated with increased nuclear binding of transcription factor NF-kappaB and AP-1 complex on electromobility shift assay. In contrast, ox-LDL (10 to 50 microg/mL) decreased TIMP-1 expression. Ox-LDL-induced increase in MMP-9 expression was abrogated by HDL (100 microg/mL). n-LDL had no significant effect on MMP-9 or TIMP-1 expression. CONCLUSIONS: These data demonstrate that unlike n-LDL, ox-LDL upregulates MMP-9 expression while reducing TIMP-1 expression in monocyte-derived macrophages. Furthermore, HDL abrogates ox-LDL-induced MMP-9 expression. Thus, ox-LDL may contribute to macrophage-mediated matrix breakdown in the atherosclerotic plaques, thereby predisposing them to plaque disruption and/or vascular remodeling.

Collagenases↗
PubMed1999

Non-radioactive hybridization in microwells using enzyme linked immune sorbent assay for detection of RT-PCR-amplified CK19- and CEA-mRNA.

PCR enzyme linked immune sorbent assay (ELISA) was developed for detection of RT-PCR-amplified cytokeratin 19 (CK19) mRNA and carcinoembryonic antigen (CEA) mRNA. The non-radioactive hybridization was performed in a streptavidin-coated microwell with digoxigenin-labeled PCR products and with biotin-labeled capture probe. PCR ELISA was proved to be expedient, simple, sensitive and safe for identification of CK19-, CEA-RT-PCR products. These results were proven by sequencing.

Bone Marrow Cells↗