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Biomedical subjects

N Shah

Publications and source records attributed to N Shah.

At least 217 records · Page 12Linked to original sources
PubMed1991

Influence of tryptophan modification upon digestion of antithrombin III by elastase.

Chemical modification of tryptophan residues in antithrombin III by dimethyl (2-hydroxy-5-nitrobenzyl) sulfonium bromide (HNBSB) generates products with similar levels of modification (equivalent to 0.9 mole 2-hydroxy-5-nitrobenzyl [HNB] incorporated/mole of antithrombin III) but with high or low affinity for heparin-Sepharose. Upon digestion with pancreatic or neutrophil elastase the low affinity forms generate a product of molecular weight form (55 kDa) not seen in digests of native antithrombin III or modified forms with high affinity for heparin. When measured as loss of activity the observed rate of digestion of the latter in the absence of heparin was more rapid than that of native antithrombin III. The differences in digestion are considered to be related to conformation at differences between the various forms.

Antithrombin III↗
PubMed1991

Role of potentially charged transmembrane residues in targeting proteins for retention and degradation within the endoplasmic reticulum.

The selective breakdown of newly synthesized proteins retained within the endoplasmic reticulum (ER) is probably mediated by the specific recognition of structural features of protein substrates by components of a degradative system. Within the alpha chain of the multisubunit T-cell antigen receptor (TCR) complex, a transmembrane sequence containing two basic amino acid residues has been shown to act as a determinant for retention and rapid degradation in the ER. We now demonstrate that single basic or acidic amino acid residues can cause targeting for retention and degradation in the ER when placed within the transmembrane domain of an integral membrane protein normally destined for the cell surface. The effect of such potentially charged residues is dependent on their relative position within the transmembrane sequence and on the nature of the amino acid side chains. The phenotypic changes induced by potentially charged transmembrane residues occur without apparent alterations of the global folding or transmembrane topology of the mutant proteins. These observations test the hypothesis that potentially charged residues within transmembrane domains can provide the basis for a motif for ER degradation and explain the selective breakdown of some proteins retained within the ER.

Amino Acid Sequence↗
PubMed1991

Improved detection of hypotension by automated noninvasive blood pressure monitoring.

This study was undertaken to determine whether the use of automated noninvasive blood pressure monitoring altered the frequency of detection of intraoperative hypotension. We retrospectively reviewed 1,861 anesthetic records from a period in 1987, when blood pressure was obtained manually by auscultation. We compared the records from 1987 with 1,716 anesthetic records from 1989, when automated blood pressure monitors were used universally. The incidences of hypotension requiring vasopressor therapy were determined during the two periods and compared using Student's two-tailed t test. The data revealed that the incidence of detected hypotension increased from 2.4 to 5.2% with the use of automated blood pressure monitors (P less than 0.00002). We conclude that at our hospital the use of automated noninvasive blood pressure monitors increases the incidence of detection of intraoperative hypotension as compared with the use of manual blood pressure measurement.

Anesthesia↗
PubMed1991

Serum lipoproteins and apolipoproteins in young normocholesterolaemic, non-diabetic Indian men with myocardial infarction.

Serum total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein A-I and apolipoprotein B were evaluated as potential indicators of the risk of coronary artery disease in young (less than 46 years) normocholesterolaemic, non-diabetic men who had previously sustained a myocardial infarction (n = 50) and in healthy age and sex matched controls (n = 122) with a similar socioeconomic background. Significant differences were observed between patients and controls in the mean concentrations of serum total cholesterol, triglycerides, low density lipoprotein cholesterol, high density lipoprotein cholesterol and apolipoprotein B, as well as in the ratios of total cholesterol to high density lipoprotein cholesterol and apolipoprotein A-I to apolipoprotein B. No significant difference was demonstrated in the concentration of apolipoprotein A-I between the two groups. Stepwise discriminant analysis indicated that apolipoprotein B was the best discriminant between patients and controls. The percentage of exact classification was 74% in patients and 66% in controls. When the patients were compared to a subset of controls (n = 50) matched for age and total cholesterol, significant differences were demonstrated only in the mean concentrations of apolipoprotein B. Discriminant analysis confirmed that the best single discriminating variable was apolipoprotein B. The results therefore indicate that in young normocholesterolaemic, non-diabetic Indian men with myocardial infarction, apolipoprotein B is superior to other lipid parameters studied, as a marker for coronary artery disease.

Adult↗
PubMed1991

Delayed haemolytic transfusion reactions in patients with sickle cell disease.

We describe two cases which illustrate the difficult diagnostic and therapeutic problems posed by delayed haemolytic transfusion reactions in patients with sickle-cell disease. The cases emphasize the need for meticulous phenotypic and serological assessment of sickle-cell patients prior to transfusion therapy.

Adolescent↗
PubMed1991

Lactose absorption by postweaning rats from yogurt, quarg, and quarg whey.

Lactose-intolerant postweaning rats were fed experimental diets including yogurt, quargs prepared from yogurt culture and buttermilk culture, and two types of whey obtained from quarg processing. After feeding each diet for a period of 7 d, absence of blood glucose elevation and occurrence of diarrhea were used as indicators of lactose malabsorption. Blood glucose assays and absence of diarrhea indicated that yogurt and quargs prepared from yogurt and buttermilk culture were well tolerated by the rats. Wheys containing the same levels of viable organisms and lactose as the quargs caused severe symptoms of diarrhea and poor lactose absorption as indicated by no changes in blood glucose levels. Plate counts and enzyme assays of gastrointestinal contents confirmed presence of viable culture organisms and beta-galactosidase activity after feeding the two types of quarg. The availability of viable organisms, the exogenous lactase activity, and especially the slow gastric emptying may all have contributed to more efficient hydrolysis and digestion of lactose from quargs and yogurt than from the wheys.

Animals↗
PubMed1990

Evidence for the role of 34-kDa galactoside-binding lectin in transformation and metastasis.

The endogenous Mr 34,000 galactoside-binding lectin (L-34) is found at elevated levels in a wide variety of neoplastic cells and correlative evidence suggests that it is involved in tumor metastasis in vivo and in transformation in vitro. We demonstrate here that introduction of recombinant L-34 into tumorigenic, weakly metastatic UV-2237-cl-15 fibrosarcoma cells results in an increased incidence of experimental lung metastases in syngeneic and nude mice. Transfection of normal BALB/c-A31 cloned fibroblasts with functional L-34 results in acquisition of anchorage-independent growth and in morphological transformation in vitro but not in tumorigenicity in vivo. These results provide direct evidence that the cellular expression of L-34 is associated with some aspects of transformation and with metastasis, but not with tumorigenicity per se.

Animals↗
PubMed1990

Influence of chemical modification of tryptophan residues on the properties of human antithrombin III.

According to the reaction conditions selected, chemical modification of tryptophan residues in antithrombin III by dimethyl (2-hydroxy-5 nitrobenzyl) sulfonium bromide (HNBSB) generated products with similar levels of modification (equivalent to 0.9 mole 2-hydroxy-5-nitrobenzyl (HNB) incorporated/mole of antithrombin III) but with high or low affinity for heparin. These products were subjected to digestion by cyanogen bromide and shown to be modified equivalently in fragment II containing Trp 189 and Trp 225 and fragment III containing Trp 49. The molar level of incorporation of HNB into these fragments was similar in the high and low affinity forms. Both high and low affinity forms showed loss of heparin cofactor activity. A recovery of heparin cofactor activity towards coagulation factor Xa was observed upon prolonged storage of low affinity forms at -70 degrees C. It is considered that the loss of high affinity for heparin upon modification of antithrombin III arises from change or stabilization of conformation associated with tryptophan modification and is not a singular property of modification of Trp 49.

Antithrombin III↗
PubMed1990

Cerebrovasculr response to CO2 in edematous brain during either fentanyl or isoflurane anesthesia.

Cerebral blood flow response to changes in PaCO2 was studied in the edematous cerebral cortex of 19 patients with malignant supratentorial tumors using laser Doppler flowmetry technology. General anesthesia for craniotomy was induced with thiopental, 3-5 mg/kg i.v., and N2O, 60% in O2. In random sequence, 8 patients were assigned to receive fentanyl, 6 +/- 1.6 (SEM). mug/kg i.v.; the other 11 received isoflurane, 0.56% end-tidal + 0.07 (SEM). After a craniotomy bone flap was turned and the dura was opened, laser flowmetry probes were placed over surgically undisturbed cortex that was known to be edematous from preoperative CT and MRI scans. Flow index measurements were first made at hypocarbia (PaCO2 = 24.2 +/- 0.9 and 21.5 +/- 2.1 mm Hg for the fentanyl and isoflurane groups, respectively). Minute ventilation was then decreased and cortical flow index was remeasured with PaCO2 = 34.2 +/- 0.6 and 33.0 +/- 0.8 mm Hg for the fentanyl and isoflurane groups, respectively. Hypocarbia during fentanyl-supplemented N2O-O2 anesthesia resulted in a cortical flow index that was 70 +/- 8% of the flow index at near normocarbia (p <0.05). During isoflurane N2O-O2 anesthesia, however, there was a wide variety of responses to hypocarbia, including three patients whose flow indices increased markedly. The mean flow index during hypocarbia was significantly (p <0.05) lower during fentanyl-N2O anesthesia than it was during isoflurane-N2O anesthesia. There was no predictable relationship between the type of brain tumor and the CBF response to hypocapnia during isoflurane-N2O anesthesia. It is concluded that, in edematous brain, cerebral cortical blood flow response to hypocarbia is more likely to be preserved during fentanyl-supplemented N2O-O2 anesthesia than it is during isoflurane-supplemented N2O-O2 anesthesia. In neuropathologic states where hyperventilation is thought to be necessary to reduce cerebral blood flow and decrease brain bulk, isoflurane may be less satisfactory than fentanyl as a supplement to N2O-O2 anesthesia.

Journal Article↗
PubMed1990

Cerebrospinal fluid pressure in patients with brain tumors: impact of fentanyl versus alfentanil during nitrous oxide-oxygen anesthesia.

The effects on the cerebrospinal fluid pressure (CSFP) of alfentanil and fentanyl were compared during nitrous oxide-oxygen (N2O-O2) anesthesia in 24 patients who had brain tumors. Monitored variables included CSFP (lumbar subarachnoid catheter), heart rate from electrocardiographic lead II, mean radial arterial blood pressure, and arterial blood gas tensions. General anesthesia was induced with thiopental, 5 mg/kg IV in divided doses, and maintained with 70% N2O in O2; ventilation was held constant (PaCO2 = 37.4 +/- 1.6 mm Hg [mean +/- SEM]). After baseline data were recorded, 16 subjects were randomly assigned to receive either 5 micrograms/kg fentanyl as an intravenous bolus or 50 micrograms/kg alfentanil as an intravenous bolus, followed by an infusion of alfentanil at 1 micrograms.kg-1.min-1. Monitored variables were continuously recorded for 15 min after opioid injection. A third group of 8 patients was studied subsequently; they received only N2O-O2 during a 15-min observation period and served as controls. Blood pressure was held constant with an intravenous infusion of 0.1% phenylephrine, as needed; noxious stimulation was carefully avoided. Cerebrospinal fluid pressure remained unchanged both in patients who received N2O-O2 alone and in those who received fentanyl-N2O-O2. By contrast, those who received alfentanil-N2O-O2 had a gradual increase in CSFP, reaching 30% above baseline values after 10 min and stabilizing thereafter. Although the absolute increase in CSFP during normocarbic alfentanil-N2O anesthesia was relatively small (9.5 +/- 1.3 mm Hg to 13.0 +/- 1.3 mm Hg [mean +/- SE], P less than 0.05), the absence of a similar effect after fentanyl administration suggests that precautionary measures such as hyperventilation are advisable if alfentanil is used for potentiating normocarbic N2O-O2 anesthesia in neurosurgical patients with intracranial mass lesions.

Adult↗
PubMed1989

Effect of a heparan sulphate with high affinity for antithrombin III upon inactivation of thrombin and coagulation factor Xa.

The kinetics of inhibition of human alpha-thrombin and coagulation Factor Xa by antithrombin III were examined under pseudo-first-order reaction conditions as a function of the concentration of heparan sulphate with high affinity for antithrombin III. The maximum observed second-order rate constant was, for the antithrombin III-thrombin reaction, 1.2 x 10(9) M-1.min-1 compared with 2.4 x 10(9) M-1.min-1 in the presence of high-affinity heparin. However, the maximum rate was catalysed by much higher concentrations of heparan sulphate (1.3 microM) than of heparin (0.025 microM). Differences were also observed in the maximal acceleration of the antithrombin III-Factor Xa interaction: 1.2 x 10(9) M-1.min-1 at 0.2 microM-heparin sulphate compared with 2.2 x 10(9) M-1.min-1 at 0.04 microM-heparin. The differences in properties of heparan sulphate and heparin were analysed by using the random bi-reactant model of heparin action [Griffith (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 5460-5464]. It was observed that the apparent binding affinity for thrombin was higher for heparan sulphate (180 nM) than for heparin (14 nM). The rate constant for transformation of the antithrombin III-Factor Xa complex into irreversible product differed between heparan sulphate (96 min-1) and heparin (429 min-1). These properties of the high-affinity heparan sulphate may be of importance in consideration of a putative role in the control of intravascular haemostasis.

Antithrombin III↗
PubMed1989

Contamination of endoscopes used in AIDS patients.

Contamination of twenty endoscopes used in patients with AIDS was assessed. The suction-biopsy, air, and water channels and the insertion tube were sampled after use, after washing in detergent, and after disinfection for 2 min in 2% alkaline glutaraldehyde. The polymerase chain reaction with Southern blotting, cell cultures, and antigen immunoassay were used to detect human immunodeficiency virus (HIV). Samples were also examined for cytomegalovirus, adenoviruses, enteroviruses, herpes simplex virus, myxoviruses, hepatitis B surface antigen, fungi, and bacteria. Seven of twenty unwashed endoscopes were contaminated by HIV. Commensal bacteria were found in all endoscopes, Candida albicans in six, Staphylococcus aureus in five, and Pseudomonas aeruginosa in five. Washing alone removed all detectable organisms from 66 of 68 contaminated sites; Neisseria spp were recovered from two air channels after washing but not after disinfection. Washing achieved a mean reduction of 4.93 (95% confidence interval 3.69-6.17) colony forming units per ml.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Where antecubital catheters go: a study under fluoroscopic control.

Fifty attempted central venous cannulations via the antecubital route were studied with fluoroscopy to determine catheter tip location. Only "catheter through needle" devices were employed. Successful central placement occurred on the first attempt in 27 cases. The major impediment to central location of the catheter tip (ten cases) was the tendency of the catheter tip to lodge at the subclavian-internal jugular vein junction. The second most common cause of noncentral location was migration of the catheter tip into the internal jugular vein (nine cases). One catheter tip was located in the contralateral subclavian vein and one ended in the external jugular vein. All of these problems were avoided by two maneuvers: 1) turning the patient's head toward the side of cannulation and applying digital pressure to the ipsilateral supraclavicular fossa, and 2) withdrawing the catheter stylet and injecting 5-10 ml of physiologic saline solution while the catheter was advanced. The only cause of unsuccessful central placement in this study was inability to pass the catheter tip past the axillary venous plexus (two patients). It is concluded that the head-turn-supraclavicular fossa pressure maneuver in combination with the stylet withdrawal-saline injection maneuver can result in greater than a 90% rate of successful central venous catheter placement.

Axillary Vein↗