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Biomedical subjects

S Sen

Publications and source records attributed to S Sen.

At least 73 records · Page 4Linked to original sources
PubMed1996

Migration of Leishmania donovani amastigotes in the cerebrospinal fluid.

A 10-year-old boy had been suffering from kala-azar (visceral leishmaniasis) for two and a half years. He failed to respond to all known anti-leishmanial treatment regimens. Even the drastic step of splenectomy failed to cure him. In November 1991, he presented with symptoms of meningitis. A diagnostic lumbar puncture revealed leishmanial amastigotes in his cerebrospinal fluid. The patient was finally cured with a course of amphotericin B, a drug known to cross the blood-brain barrier.

Amphotericin B↗
PubMed1996

Synthesis of some new 2-methyl-4-(substituted benzylidene)1-phenyl-1,2,4 triazolo (3,4,-b) 1,4,5 thiadiazole as potential AChE inhibitory agents.

4-(1-aminophenyl)-1,2,4-triazolo[3,4,-b]1,3,4-thiadiozole (2) was prepared by treatment of 4-(1-aminophenyl)-5-mercapto-4-amino-1,2,4-S-triazole with carbondisulfide and KOH in methanol. This on further reaction with different 2-methyl-4-(substituted benzylidene)-oxazolin-5-ones gave 2-methyl-4-(substituted benzylidene)-1-phenyl-1,2,4[triazolo[3,4,-b]1,3,4-thiadiozoles. The compounds were screened for AChE inhibitory activity.

Animals↗
PubMed1995

Formation of a free radical of the sulfenylimine type in the mouse ribonucleotide reductase reaction with 2'-azido-2'-deoxycytidine 5'-diphosphate.

Mouse and Escherichia coli ribonucleotide reductases (RR) both belong to the same class of RR, where the enzyme consists of two non-identical subunits, proteins R1 and R2. A transient free radical was observed by EPR spectroscopy in the mouse RR reaction with the suicidal inhibitor 2'-azido-2'-deoxycytidine 5'-diphosphate. The detailed hyperfine structure of the EPR spectrum of the transient radical is somewhat different for the mouse and previously studied E. coli enzymes. When the positive allosteric effector ATP was replaced by the negative effector dATP, no transient radical was observed, showing that 'normal' binding of the inhibitor to the substrate binding site is required. Using the mouse protein R2 mutants W103Y and D266A, where the mutations have been shown to specifically block long range electron transfer between the active site of the R1 protein to the iron/radical site in protein R2, no evidence of transient radical was found. Taken together, the data suggest that the radical is located at the active site in protein R1, and is probably of the sulfenylimine type.

Animals↗
PubMed1995

Comparison of mortality from acute myocardial infarction in patients receiving anistreplase with those not receiving thrombolysis.

Within 1 year, 434 patients were admitted to 14 hospitals with suspected acute myocardial infarction (AMI) < or = 4 hours after the onset of symptoms. Group A consisted of 171 patients (39%) treated with thrombolysis, and group B consisted of 263 patients (61%) with contraindications. Patients in group A more likely had a "definite AMI" (92%; group A1) than patients in group B (67%; group B1). Group B1 had 277 contraindications (1.6/per patient) with increased risk for life-threatening bleeding being the most frequently recorded at admission. The in-hospital mortality in group A1 was 7% (11 of 158) and in group B1, 27% (47 of 177) (p < 0.0001). Age and type of therapy (thrombolysis or no thrombolysis) were identified as independent predictors of increased mortality (p < 0.0001 and < 0.05, respectively). Thus, although most patients with an AMI are excluded from thrombolytic therapy because of contraindications, our data suggest that their in-hospital mortality is unexpectedly high. Further evaluation of this group of patients is warranted to define the impact of contraindications as an independent factor of mortality.

Aged↗
PubMed1995

p53 gene mutations with chromosome 17 abnormalities in chronic myelogenous leukemia blast crisis patients persist in long-term cell lines but may be acquired in acute myeloid leukemia cells in vitro.

Altered p53 tumor suppressor genes have been described in various human malignancies, including in chronic myelogenous leukemias (CML) and acute myelogenous leukemias (AML), as well as their derivative cell lines. It has been proposed that this gene mutation may be less frequent in myeloid leukemia patients than in myeloid leukemia cells lines and that the latter acquire these mutations during growth in vitro. We investigated this possibility by studying p53 gene alterations in matched samples of fresh leukemic cells and their respective derivative cell lines obtained from two CML blast crisis and one AML patient. No gross structural abnormalities were detected in the p53 gene in any of the samples analyzed. Discrete mutations in the gene in the two CML blast crisis samples and in all three derivative cell lines were, however, detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analyses and DNA sequencing. Cytogenetic analyses revealed either numerical or structural, as well as numerical, abnormalities of chromosome 17 in their karyotypes. Cells from the two CML blast crisis patients had two different mutations which were maintained as the sole mutations in the cell lines. The mutation detected in the AML cell line was, however, not detectable in the parental fresh leukemic cells. Our findings demonstrate that p53 mutations and chromosome 17 abnormalities occurring in CML blast crisis patients persist in long-term cell lines but that mutations not detectable in AML patients may indeed be acquired in cell lines established from them in vitro.

Adult↗
PubMed1995

More rapid, complete, and stable coronary thrombolysis with bolus administration of reteplase compared with alteplase infusion in acute myocardial infarction. RAPID Investigators.

BACKGROUND: Early restoration and maintenance of normal (TIMI 3) blood flow during acute myocardial infarction is critical for optimal preservation of left ventricular function and survival. Recombinant plasminogen activator (r-PA, reteplase) is a nonglycosylated deletion mutant of wild-type tissue-type plasminogen activator (TPA) that has been shown to achieve more rapid and complete thrombolysis compared with other plasminogen activators in animal models. METHODS AND RESULTS: The RAPID Trial was designed to test the hypothesis that bolus administration of one or more dosage regimens of r-PA was superior to standard-dose alteplase (TPA) in achieving infarct-related artery patency 90 minutes after initiation of treatment. Six hundred six patients with acute myocardial infarction were randomized to one of four treatment arms: (1) TPA 100 mg i.v. over 3 hours, (2) r-PA as a 15-MU single bolus, (3) r-PA as a 10-MU bolus followed by 5 MU 30 minutes later, or (4) r-PA as a 10-MU bolus followed by 10 MU 30 minutes later. Coronary arteriography was performed at 30, 60, and 90 minutes after initiation of treatment and at hospital discharge. The 10 + 10-MU r-PA group achieved better 90-minute and 5- to 14-day TIMI 3 flow (63% [CI, 55% to 71%] versus 49% [41% to 57%], P = .019, and 88% [82% to 94%] versus 71% [63% to 79%], P < .001, respectively) than the TPA group. The TIMI 3 flow in the 10 + 10-MU r-PA group at 60 minutes was equivalent to that in the TPA group at 90 minutes (51 versus 49%). Global ejection fraction and regional wall motion in the 10 + 10-MU r-PA group were superior to those of the TPA group at hospital discharge (53 +/- 1.3% versus 49 +/- 1.3%, P = .034; -2.19 +/- 0.12 versus -2.61 +/- 0.13 SD per chord, P = .02, respectively). The 15-MU and 10 + 5-MU r-PA patency and left ventricular function results were similar to those of the TPA and inferior to those of the 10 + 10-MU r-PA group. Bleeding complications were similar between the groups. CONCLUSIONS: r-PA given as a double bolus of 10 + 10 MU achieves more rapid, complete, and sustained thrombolysis of the infarct-related artery than standard-dose TPA, without an apparent increased risk of complications. This was associated with improved global and regional left ventricular function at hospital discharge.

Coronary Angiography↗
PubMed1995

Measurement of weekly prostate specific antigen levels in patients receiving pelvic radiotherapy for nonprostatic malignancies.

PURPOSE: To study the response of nonmalignant prostatic tissue to ionizing irradiation in terms of the resultant changes in serum prostate specific antigen (PSA) levels. METHODS AND MATERIALS: Weekly serum PSA values were determined during radiotherapy (RT) in nine patients ("treatment group") without clinical evidence of prostate cancer (PC), and who received pelvic RT for other indications. Slopes for the rate of change in PSA was determined using model: log PSA = beta 0 + beta 1*week + beta 2*week2 + error. These results are compared with 17 normal volunteers ("control group") who were not exposed to ionizing irradiation. An attempt is made to compare any similarities and differences in subsets of 64 T1-T4N0M0 PC patients who received pelvic RT. RESULTS: An elevation in the serum PSA levels were noted in eight of nine patients in the "treatment group" with a median time of 4.2 weeks to reach the maximum serum PSA values. After an initial increase, PSA values declined. In some patients, manifold increase in PSA was noted, for example, from 1.8 to 13.5 ng/ml and 3.3 to 9.8 ng/ml in two patients. The PSA increase ranged from 50-650%. The median slope was 0.601 week-1 (range 0.192-3.045 week-1). No such increases were seen in the "control group" (median slope = 0.03 week-1; range, 0.18-0.13 week-1). When differences between the mean increase/decrease for each week compared to pretreatment values were analyzed, the irradiated group had statistically significant elevations in the PSA for weeks 3 (p = 0.034), 4 (p = 0.035), and 5 (p = 0.024). A similar trend of increasing PSA levels during radiotherapy was noted in prostate cancer patients whose initial PSA values were < or = 20 ng/ml: whereas positive slopes (i.e., increasing PSA levels during radiotherapy course) was seen in 7.1% of those with > 20 ng/ml preradiotherapy PSA values, such trends were seen in 52.7% of those with < or = 20 ng/ml preradiotherapy PSA values. CONCLUSIONS: (a) Incidental exposure of noncancerous prostate to ionizing irradiation appears to lead to an initial elevation followed by a decline in serum PSA. (b) Similar elevations in serum PSA levels are seen in over 50% of prostate cancer patients with < or = 20 ng/ml pretreatment PSA. (c) Acinal cell death and sudden release of PSA into the circulation is the most likely explanation for our observations, although other mechanism cannot be excluded. (d) Our observations have to be considered in modeling PSA kinetics induced by RT and in correlating such kinetics to long-term outcomes. (e) Our findings in the control group indicate that there appears to be no significant variation in serum PSA over many weeks under physiological conditions in normal healthy ambulatory men.

Adult↗
PubMed1995

Myocardial fibrosis and stiffness with hypertrophy and heart failure in the spontaneously hypertensive rat.

BACKGROUND: Fibrosis is commonly found in association with cardiac hypertrophy and failure, but the relation of the connective tissue response to the development of impaired cardiac function remains unclear. We examined passive myocardial stiffness, active contractile function, and fibrosis in the spontaneously hypertensive rat (SHR), a model of chronic pressure overload in which impaired cardiac function follows a long period of stable hypertrophy. METHODS AND RESULTS: We studied the passive and active mechanical properties of left ventricular (LV) papillary muscles isolated from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at the ages of 12 months and 20 to 23 months. Seven of 15 SHR between 20 and 23 months of age had findings consistent with heart failure (SHR-F). In comparison to preparations from WKY rats and nonfailing SHR (SHR-NF), papillary muscles from the SHR-F group demonstrated increased passive stiffness (central segment exponential stiffness constant, kcs: SHR-F 95.6 +/- 19.8, SHR-NF 42.1 +/- 9.7, WKY rats 39.5 +/- 9.5 (mean +/- SD); SHR-F P < .01 versus SHR-NF, WKY rats). The increase in stiffness was associated with an increase in LV collagen concentration (SHR-F 8.71 +/- 3.14, SHR-NF 5.83 +/- 1.20, WKY rats 4.78 +/- 0.70 mg hydroxyproline/g dry LV wt; SHR-F P < .01 versus SHR-NF, WKY rats); an increase in interstitial fibrosis, as determined histologically (SHR-F 13.5 +/- 8.0%, SHR-NF 4.9 +/- 2.1%, WKY rats 3.6 +/- 0.8%; SHR-F P < .01 versus SHR-NF, WKY rats); and impaired tension development (SHR-F 3.18 +/- 1.27, SHR-NF 4.41 +/- 1.04, WKY rats 4.64 +/- 0.85 kdyne/mm2; SHR-F P < .05 versus SHR-NF; P < .01 versus WKY rats). CONCLUSIONS: The development of heart failure in the aging SHR is associated with marked myocardial fibrosis, increased passive stiffness, and impaired contractile function relative to age-matched nonfailing SHR and nonhypertensive control animals. These data suggest that fibrosis or events underlying the connective tissue response are important in the transition from compensated hypertrophy to failure in the SHR.

Aging↗
PubMed1995

Allopurinol reduces the severity of peritoneal adhesions in mice.

A study was designed to investigate the possibility of reducing peritoneal adhesion formation in mice by pretreatment with allopurinol. Allopurinol, at a dose of 35 mg/kg of body weight/d significantly reduced the severity of peritoneal adhesions (P < .001), and also the neutrophil response to ischemia (P < .05). Tissue myeloperoxidase activity at the site of ischemic injury was significantly lower in the allopurinol-treated mice at the end of 2 weeks (P < .001). However, xanthine oxidase was undetectable in both control and allopurinol-treated mice. These observations suggest that allopurinol reduces the severity of peritoneal adhesion formation in mice, possibly by reducing the neutrophil response to ischemia.

Allopurinol↗
PubMed1995

Antiulcer and gastric secretory activity of N-octanoyl gamma-aminobutyric acid.

A new gamma-aminobutyric acid derivative synthesised in this laboratory, N-octanoyl gamma-aminobutyric acid was found to possess antinociceptive activity but no anticonvulsant activity. The effect of the compound on gastric lesions produced by aspirin, ethanol and stress in rats, was studied and the compound was found to possess effective antiulcer action. Even though, N-octanoyl gamma-aminobutyric acid did not produce a significant change in the volume of gastric acid secretion, however, it decreased the acidity and peptic activity and significantly enhanced the gastric mucus secretion.

Animals↗
PubMed1995

The spontaneously hypertensive rat as a model of the transition from compensated left ventricular hypertrophy to failure.

Studies of hemodynamics and intrinsic left ventricular myocardial function are carried out to investigate the transition from stable hypertrophy to cardiac decompensation in the aging (18-24 months) spontaneously hypertensive rat (SHR). Echocardiographic data in awake animals demonstrate increased end-diastolic and end-systolic volumes and depressed ejection fractions in left ventricles from SHR with failure (SHR-F) as compared to age matched hypertensive (SHR-NF) and non-hypertensive control animals (WKY). Cardiac catheterization data in anesthetized animals demonstrate depression of both systolic pressure and +dP/dt, and elevated end-diastolic pressure in the SHR-F relative to the two control groups. Since loading conditions and altered demand states may contribute to altered ventricular function, studies of isolated perfused hearts were carried out which demonstrate impaired systolic stress development in the SHR-F group under conditions in which loading conditions are controlled; in addition, it is observed that increasing perfusion pressure by 30 mm Hg has little effect on function. Depression of systolic function and increases in passive stiffness of isolated muscle preparations from the SHR-F indicate impairment of systolic and diastolic function at the tissue level. While all of the preparations studied have potential shortcomings, an integration of findings from these complementary approaches supports the conclusion that heart failure develops in the aging SHR. Furthermore, these data suggest that impaired function is due to changes in the intrinsic properties of the myocardium and that the connective tissue response may play an important role. These studies, in conjunction with the findings of others who have studied the aging SHR, provide support for the use of the aging SHR as a model of the transition from compensated hypertrophy to failure.

Animals↗
PubMed1995

Vectorcardiographic monitoring to assess early vessel patency after reperfusion therapy for acute myocardial infarction.

Reperfusion therapy has lowered mortality in patients suffering from acute myocardial infarction. Failure to reperfuse is associated with an increased short- and long-term mortality. In a prospective study we used dynamic vectorcardiography to monitor 96 patients with acute myocardial infarction treated with reperfusion therapy to non-invasively assess coronary patency. The results from continuous monitoring were compared to those obtained from angiography. By using trend-analysis of QRS vector difference and ST vector magnitude, we were able to correctly identify 58 of the 70 patients (83%) with a reperfused infarct-related artery, and 19 of the 26 patients (73%) with a persistently occluded artery demonstrated at an early angiogram (diagnostic accuracy 80%). In patients with high-grade collateral flow to the infarct-related area, the results of the vectorcardiographic monitoring and of angiography showed the largest disagreement, whereas the accuracy of vectorcardiographic monitoring was high: 88% among patients without collaterals. The present results suggest that QRS complex and ST segment vectorcardiographic monitoring is a useful tool for assessing early coronary artery patency, and that dynamic vectorcardiography may help in identifying candidates for emergency coronary angiography.

Acute Disease↗