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Biomedical subjects

K Foster

Publications and source records attributed to K Foster.

At least 19 recordsLinked to original sources

Altered insulin receptor processing and membrane lipid composition in erythrocytes of cirrhotic patients.

Insulin binding and insulin receptor down-regulation characteristics were evaluated, as well as cholesterol and phospholipid levels in erythrocytes from 22 patients with liver cirrhosis. These parameters were correlated with clinical characteristics and with scores related to severity of the liver injury. Nine healthy subjects were studied as a control group. It was observed that insulin binding was generally greater in patients than in controls because of an increase in surface insulin receptor numbers, rather than from a change in receptor affinities. In cirrhotic patients, the erythrocyte insulin receptors did not undergo the normal down-regulation process but, in most cases, increased in response to insulin incubation. The alterations in insulin processing characteristics were more frequent in patients with alcoholic cirrhosis and more severe liver impairment and correlated with the changes in the lipid composition of erythrocyte membranes. In particular, an increase in the cholesterol to phospholipid molar ratio and a decrease in polyunsaturated fatty acid content of phospholipids in erythrocyte membranes of cirrhotic patients was associated with impairments in insulin receptor processing. Similar changes in insulin receptor processing were observed when the molar ratio of cholesterol to phospholipid in normal erythrocytes was modified in vitro by incubation with cholesterol-rich liposomes.

Adult

Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridization.

The stromelysins are members of a family of extracellular matrix metalloproteinases. These enzymes may erode the connective tissue in atherosclerotic plaques, leading to fissuring and acute thrombotic events. Cell-specific stromelysin expression in human atherosclerotic plaques was studied by in situ hybridization and immunocytochemistry. Sections were taken from nine coronary arteries: eight with well-established plaques and one normal. Unambiguous signals were seen in five plaques, two were inconclusive, and the remaining sample was negative, as was the normal coronary artery. Stromelysin mRNA transcripts were localized to isolated individual cells, some of which were smooth muscle, in the plaque cap, intima, and adventitia, but not the media. Expression was also seen in large clusters of macrophages that contained intracellular lipid deposits. The isolated expression of stromelysin by smooth muscle cells may reflect local connective tissue remodeling associated with growth and the formation of the plaque, whereas the more extensive expression associated with macrophages may be of greater pathological significance, contributing to the destabilization of the extracellular matrix and eventual plaque rupture.

Arteriosclerosis

Role of pertussis toxin-sensitive guanosine triphosphate-binding proteins in the response of erythroblasts to erythropoietin.

Human progenitor-derived erythroblasts have been recently shown to respond to erythropoietin (Epo) with an increase in intracellular free calcium concentration [Cac]. To explore the role of guanosine triphosphate (GTP)-binding proteins in mediating the rise in [Cac], single day 10 erythroid burst forming unit (BFU-E)-derived erythroblasts loaded with Fura-2 were pretreated with pertussis toxin (PT), stimulated with Epo, and [Cac] measured over 18 minutes with fluorescence microscopy coupled to digital video imaging. The [Cac] increase in day 10 erythroblasts stimulated with Epo was blocked by pretreatment with PT in a dose-dependent manner but not by heat-inactivated PT. These observations provided strong evidence that a PT-sensitive GTP-binding protein is involved. To further characterize the GTP-binding protein, day 10 erythroblast membrane preparations were solubilized, electrophoresed, and immunoblotted with antibodies specific for the known PT-sensitive G-protein subunits: the three subtypes of Gia (1,2, and 3) and Goa, Gia1 or Gia3 and Gia2 were identified but no Goa was found. To examine the influence of Epo on adenylate cyclase activity, day 10 erythroblasts were initially treated with Epo, isolated membrane preparations made, and cyclic adenosine monophosphate (cAMP) production by adenylate cyclase in membrane preparations in the presence of theophylline measured. Epo did not inhibit but significantly stimulated adenylate cyclase activity. However, the mechanism of increase of [Cac] appears to be independent of adenylate cyclase stimulation because treatment of erythroblasts with the cell-permeant dibutyryl cAMP failed to increase [Cac]. In summary, pertussis toxin blocks the increase in [Cac] in erythroblasts after Epo stimulation suggesting that this response is mediated through a pertussis toxin-sensitive GTP-binding protein. Candidate PT-sensitive GTP-binding proteins identified on day 10 erythroblasts were Gia 1, 2, or 3, but not Goa.

Adenylate Cyclase Toxin

Effect of psychological factors on risk behavior of human immunodeficiency virus (HIV) infection among intravenous drug users (IVDUs).

The effect of psychological factors on drug and sexual behaviors in relation to HIV infection was investigated among 262 IVDUs in methadone clinics in New York City. Among female IVDUs, the HIV positive subjects reported larger numbers of sex partners than those subjects who were HIV negative, and those who had larger numbers of sex partners were more likely to be depressed. The IVDUs who had larger numbers of needle-sharing partners at shooting galleries were more likely to be HIV positive. Intervention programs should focus on IVDUs who are sexually active females, sharing needles at galleries, still using heroin and cocaine, and who began using heroin at an early age.

Adolescent

Polymerase chain reaction and Q beta replicase amplification.

The polymerase chain reaction (PCR) and Q beta replicase are two methods in which nucleic acid polymerases are used for amplification. Although these approaches share many similar problems concerning target contamination and probe specificity, they differ dramatically in their mechanisms of action and modes of application. The PCR method amplifies target sequences between two priming oligonucleotides and in essence amplifies a portion of the analyte. Q beta replicase, on the other hand, amplifies a specific template molecule hybridized to target sequences and therefore amplifies a signal component of the system. For this reason, Q beta replicase amplification has applications in areas other than for the detection of nucleic acid sequences. The requirements for application and the advantages of both PCR and Q beta replicase amplification are reviewed.

DNA-Directed DNA Polymerase

Behavioral risk factors of human immunodeficiency virus infection among intravenous drug users and implications for preventive interventions.

Risk behaviors for HIV infection in relation to drug and sexual activities among 262 intravenous drug users (IVDUs) from methadone clinics in New York City were investigated using a structured questionnaire in 1986. The overall seroprevalence rate was 60.1 per cent. Intravenous heroin and cocaine users were found to be significantly more likely to be HIV positive than those who used heroin and cocaine intranasally. Among female IVDUs, excluding prostitutes (defined by self-report of sex for money or drugs), the HIV positive participants reported higher numbers of sex partners than those participants who were HIV negative. The female IVDUs who reported prostitution during the last 12 months were less likely to be HIV positive than those who did not. All males who reported passive anal and oral sex without using condoms during the last 12 months were found to be HIV positive. All female prostitutes who reported use of condoms during the last 12 months were found to be HIV negative. Interventions in methadone maintenance programs should focus on the IVDUs who are still using heroin, cocaine, and marijuana; sexually active females; and those IVDUs not using condoms (particularly among prostitutes).

Acquired Immunodeficiency Syndrome

Electrically produced artificial ventilation.

The induction of inspiration by delivering a burst of short-duration stimuli to body-surface electrodes is over a century old. The authors have used the term electroventilation to describe the technique. Inspiration can be produced with stimuli applied to electrodes placed bilaterally at the base of the neck, over the phrenic nerve motor points. Transchest electrodes placed anterior to the axillae can be used to stimulate the long thoracic and phrenic nerves. Paraxiphoid electrodes can be used to stimulate the phrenic nerves as they enter the diaphragm. With any of these electrode placements, inspired volumes in excess of spontaneous tidal volumes can be achieved in man, baboon, and dog. Of major importance is the need to use short-duration (less than 10-microseconds) pulses in the train of stimuli that produces contraction of the inspiratory muscles. The duration of inspiration is determined by the duration of the train, which is typically 0.5-1 s. The use of short-duration pulses minimizes the risk of producing cardiac arrhythmias and results in very little sensation at the skin.

Animals

A distinction in vitro between rat liver phosphatidate phosphatase and phospholipase C.

Hepatocellular membranes (1000 X g) containing membrane-associated, labeled phosphatidic acid were incubated (1-30 min) with 2 mM oleate or 5 mM bromobenzene in the presence or absence of various metals and NaF. Under the appropriate incubation conditions, membranes displayed rapid and significant oleate- and bromobenzene-dependent increases in the dephosphorylation of labeled phosphatidic acid. However, oleate and bromobenzene activated the dephosphorylation of phosphatidate by phosphatidate phosphatase and phospholipase C, respectively. This conclusion is supported by the observation that the phosphatase stimulated by oleate is: (1) Mg2+ -dependent; (2) inhibited by other metals, such as Ca2+; (3) inhibited by NaF; (4) specific for phosphatidic acid; and (5) associated with a rise in liver cell triacylglycerol production. Bromobenzene, however, activated a phospholipase C that is: (1) stimulated by various metals, such as Mg2+, Ca2+ and Ba2+; (2) insensitive to NaF; (3) associated with the degradation of various membrane phospholipids; (4), associated with liver cell injury; and (5) not associated with a rise in liver cell triacylglycerol formation. These results suggest that under appropriate conditions in vitro the dephosphorylation of phosphatidic acid can be used to assess changes in phosphatidate phosphatase and/or phospholipase C activity. The distinction between these enzymes is important, since phosphatidate phosphatase and phospholipase C regulate key steps in phospholipid biosynthesis and degradation, respectively.

Animals

A comparison of nalbuphine and meperidine in treatment of postoperative pain.

The analgesic efficacy and side effect profile of nalbuphine 20 mg IV and of nalbuphine 40 mg IV were compared to those of meperidine 75 mg IM in the immediate postoperative period. Pain intensity, pain relief, additional analgesic requirements and the overall acceptability of the treatment were recorded for 150 patients. No significant differences were found between the groups for any of the efficacy variables. Peak analgesic effects occurred at 15 minutes in both nalbuphine groups and at 30 minutes in the meperidine group. The mean time to additional analgesic medication was approximately 207 minutes in each group. The incidence of nausea and vomiting with meperidine was 22 per cent (95 per cent confidence interval 10 to 34 per cent) and with nalbuphine 20 mg the incidence was two per cent (95%CI -2 to 6 per cent). This difference was significant (p less than 0.01). The difference between nalbuphine 40 mg (10 per cent, 95%CI 1 to 19 per cent) and meperidine, was not considered statistically significant (p = 0.17). The analgesic efficacy of nalbuphine 20 mg was indistinguishable from that of nalbuphine 40 mg and from that of meperidine 75 mg. The significantly lower incidence of nausea and vomiting with nalbuphine is a major advantage for a recovery room analgesic.

Abdomen

Medical facilities used by heroin users.

There is little information about the extent of contact between heroin users and medical facilities. In this study of heroin users from general practice we found an increase in the attendance of patients after the onset of heroin use and that a high proportion of appointments were made at general practices compared with hospital departments.

Adolescent