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Biomedical subjects

P Kulkarni

Publications and source records attributed to P Kulkarni.

52 records · Page 3Linked to original sources

Evidence for the presence and characterization of angiotensin II receptors in rat anterior pituitary membranes.

Previous work from this laboratory (1) indicates that angiotensin II (AII) can affect release of several anterior pituitary hormones, both in vivo and in vitro. To ascertain whether specific receptors mediate the effects of AII on the anterior pituitary, specific binding as well as the kinetics of [125I] AII binding to rat anterior pituitary membranes were analyzed. Binding of [125I] AII was rapid, reaching equilibrium within 4 min at 37 C. Specific binding was approximately 90%. Increasing concentrations of ligand resulted in saturation of binding, with equilibrium attained at [125I] AII = 2 nM. Scatchard analysis of the data indicated a single class of binding sites, with an equilibrium dissociation constant, Kd = 0.49 nM, and a maximum binding capacity of 40 fmol/mg protein. Specific binding was directly proportional to membrane protein concentration (range 20-240 micrograms protein). Binding was competitively inhibited on an equimolar basis by (Sar1, Ala8) AII (Saralasin), a specific AII receptor antagonist. The decapeptide Angiotensin I was about 10-20-fold less potent in inhibiting specific AII binding. These studies demonstrate and characterize specific receptor sites for AII in the anterior pituitary gland and offer additional evidence for a role of AII in the regulation of anterior pituitary hormone secretion.

Angiotensin II↗

Localization of anti-mitochondrial antibody in experimental canine myocardial infarcts.

Alterations in cell and subcellular membrane integrity occur during evolving ischemic myocardial injury. We tested the hypothesis that an antibody against human liver mitochondria [anti-mitochondrial antibody developing in a patient with primary biliary cirrhosis] could identify altered cell membrane integrity in experimental canine myocardial infarcts. The proximal left anterior descending coronary arteries of 12 dogs were ligated and 1 hr later 131I-labeled F(ab')2 fragments from either a control human IgG (6 dogs) or anti-mitochondrial IgG (6 dogs) were injected. The 131I-labeled F(ab')2 anti-mitochondrial fragments concentrated maximally in the central infarct subendocardium [infarct-to-normal ratio of 9.2 +/- 3.5 (mean +/- SD) vs. 4.6 +/- 3.3 for control F(ab')2 IgG, P < 0.05]. There was also 1 1/2- to 2-fold greater anti-mitochondrial antibody F(ab')2 accumulation in the central infarct epicardium and the peripheral infarct subendocardium and subepicardium. Thus, an anti-mitochondrial antibody obtained from a patient with primary biliary cirrhosis concentrates in irreversibly damaged myocardium after experimental canine myocardial infarction. Presumably this occurs because of altered cell membrane integrity, which allows exposure of mitochondria to the anti-mitochondrial antibody. The F(ab')2 fragments of anti-mitochondrial antibodies labeled with suitable radionuclides should allow noninvasive scintigraphic detection of experimental acute myocardial infarcts.

Animals↗

Prodrug approaches to enhancement of physicochemical properties of drugs IX: acetaminophen prodrug.

The synthesis, hydrolysis rate, and bioavailability of 1-(p-acetaminophenoxy)-1-ethoxyethane, an acetaminophen prodrug, are described. The prodrug is less soluble than acetaminophen and stable at neutral pH. However, in an acidic environment, the compound cleaves rapidly, generating acetaminophen. When both the prodrug and acetaminophen were administered to dogs in equivalent amounts, the blood acetaminophen levels were comparable.

Acetaminophen↗

Postneonatal infant mortality in infants to a neonatal intensive care unit.

The postneonatal infant mortality (PNIM) of 2,205 infants admitted to a neonatal intensive care unit from January 1971 to December 1974 was 44 in 1,000 infants who survived to age 28 days. This rate is approximately ten times that of the general population. Congenital malformations (59%), infections (12%), sudden infant death syndrome (10%), and asphyxial brain damage (10%) were the most common causes of death. One third (26) of the infants remained in the hospital whereas two thirds (52) had been dismissed prior to death. All who remained in the hospital plus 36 who had been dismissed died of severe illnesses that were incompatible with prolonged survival. The remaining PNIM was 10 in 1,000 neonatal survivors. This rate is still twice that of the general population. These deaths occurred in infants who were apparently well at the time of dismissal and subsequent examinations. Sudden infant death syndrome and infections constituted the largest portion of this mortality. Factors contributing to mortality in this group were poor socioeconomic status and low birth weight. Maternal age, race, marital status, and neonatal illnesses including apnea were not significantly related. Factors that appear to be important in the birth of high-risk infants continued to be operative in the postneonatal period, and contribute to a high mortality in apparently normal infants dismissed from the neonatal intensive care unit.

Abnormalities, Multiple↗

Confirmation of trisomy 22 by trypsin-giemsa staining.

A small-for-dates male infant with mental retardation, microcephaly, malformed ears, preauricular sinuses, epicanthal folds, micrognathia, congenital heart diseases, micropenis, and micropolygyria of the parietal and occipital lobes of the cerebral cortex was shown to have a 47,XY,+22 karyotype by trypsin-giemsa banding. Review of reported cases confirms that there may be distinctive trisomy 22 syndrome.

Azure Stains↗

Ewing's sarcoma with cutaneous metastasis--a rare entity: report of three cases.

Ewing's sarcoma (ES) is a small round cell tumor, usually arising from flat bones and diaphyseal region of long bones. It is commonly found in the first two decades of life. It is curable when diagnosed in the localized stage and requires multimodality treatment. ES is a chemosensitive tumor. It metastasizes commonly to lung, pleura and other bones. Less common sites of metastasis are lymph nodes, CNS and liver. Skin metastasis is extremely uncommon. It occurs in up to 9% of all patients with cancer. Growth pattern of cutaneous metastasis is unpredictable and may not reflect that of primary tumor. We hereby report three cases of Ewing's sarcoma that developed skin metastasis.

Adolescent↗

Biocompatible coatings with high albumin affinity.

A process was developed to coat complex medical devices with a thin, transparent, biocompatible film. The film is based on silicone rubber (SR) but has higher albumin affinity than SR. Two polymer forms have been developed: one substitutes hydroxyl groups (OH), the other, 16 carbon acyl groups (C16) in the siloxane side chains. Oxymercuration/demercuration or hydroboration reactions can be used. SEM reveals film surfaces are smooth, uniform, and featureless. ATR/FTIR spectra and advancing/receding water contact angle measurements confirm the presence of surface OH groups and suggest the presence of surface acyl groups. Albumin adsorption and retention are markedly enhanced for surface OH and C16 concentrations as low as 5% reaction yield. Kinetics, isotherm, and competitive albumin/fibrinogen adsorption studies suggest that surface hydroxylation, and perhaps C16 acylation as well, markedly improve the albumin affinity, but not the fibrinogen affinity, of this material. The SR film can be durably coated on several materials, making it possible to favorably treat many blood-contacting devices, using a simple immersion process.

Biocompatible Materials↗

Calcium 45 autoradiography and dual-isotope single-photon emission CT in a canine model of cerebral ischemia and middle cerebral artery occlusion.

PURPOSE: To determine whether transient ischemia can be separated from permanent ischemia via calcium 45 autoradiography and to assess the applicability of dual isotope single-photon emission CT (SPECT) in the evaluation of cerebral blood flow. METHODS: We examined calcium influx in 12 dogs (group A) by using whole-brain calcium 45 autoradiography: Animals received 250 microCi/kg 24 hours after 30-minute (n = 6) or permanent (n = 6) middle cerebral artery (MCA) occlusion. Forty-eight hours after MCA occlusion, 5-mm coronal brain sections were fixed for either autoradiography or pathologic examination. In a separate study, 9 mongrel dogs (group B) were given 250 microCi/kg calcium 45 and a mean dose of 700 microCi/kg technetium Tc 99m hexamethylpropyleneamine oxime intravenously. A silicone plug was then injected into the internal carotid artery and angiography was performed to verify MCA occlusion. A 10th (control) animal did not undergo occlusion. In an 11th animal, placement of the plug could not be achieved and a slurry of microfibrillar collagen was injected into the carotid artery. No angiography was performed in animals 10 and 11. After occlusion, each animal was injected with a mean dose of 126 microCi/kg simultaneous acquisition for technetium 99m and 123I-iodoamphetamine. RESULTS: In group A, all animals who had permanent MCA occlusion showed infarction and increased calcium 45 uptake in infarcted territories. None of the animals who had 30-minute occlusion had either increased calcium 45 uptake or infarction at 48 hours. In group B, 7 or 10 dogs had SPECT findings that were consistent with the calcium autoradiographic marker for ischemia. One animal died during the procedure and 1 dog served as a control. CONCLUSION: Calcium 45 autoradiography allowed distinction between areas of temporary and permanent occlusion. Iodoamphetamine imaging was not consistently sensitive to that level of ischemia. Timing of calcium influx may lead to insight that could impact timing of pharmacologic or endovascular intervention.

Amphetamines↗

Design of an oxygenator with enhanced gas transfer efficiency.

Membrane oxygenator designs were examined with particular attention to the influence of radial and axial flow around windings of microporous polypropylene hollow fibers. Oxygen transfer performance was calculated, employing the Mockros-Leonard modified heat transfer analysis and Curtis-Eberhart normalization methods. Flow through an Avecor Affinity oxygenator was imaged by gamma scintigraphy using a bolus injection of 99mTc-DTPA. Experimental mass transfer correlations were developed for this oxygenator using saline. The oxygen exchange of the Avecor Affinity was slightly less than that for the Medtronic Maxima or COBE Optima models, which are based on similar designs.

Biomedical Engineering↗