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Biomedical subjects

S C Martin

Publications and source records attributed to S C Martin.

At least 55 records · Page 3Linked to original sources

ATP activates a Ca(2+)-dependent Cl- current in the rat thyroid cell line, FRTL-5.

The effect of external ATP on both the membrane potential and the transmembrane current of the thyroid cell line FRTL-5 has been investigated in the patch-clamp whole-cell recording configuration. In the resting situation the membrane potential is around -70 mV and the membrane acts like a K(+)-sensitive electrode. Application of ATP at concentrations higher than 1 microM elicited an increase in Cl- conductance, responsible for a membrane depolarization which could be blocked by preincubation with the P2-antagonist quinidine. Chelation of intracellular Ca2+ also blocked the ATP induced changes in membrane potential and Cl- current. Intracellular perfusion with inositol trisphosphate (IP3) (50 microM) also stimulated a Cl- current which mimicked the response induced by ATP. ATP is able to initiate a response in the absence of extracellular Ca2+, but also opens a Ca(2+)-influx pathway, as demonstrated by a secondary response upon Ca2+ readmission in the external medium, in the continued presence of ATP. ADP and ATP gamma S were able to mimic the ATP response, whereas AMP and adenosine were unable to elicit a Cl- current. The P2X receptor agonist alpha,beta-methyleneATP was without effect as was the P2Y receptor agonist 2-methylthio ATP. We conclude that ATP is able to elicit a large IP3-mediated Ca(2+)-dependent Cl- current and membrane depolarization via a novel P2-type purinergic receptor.

Adenosine Triphosphate↗

Use of sentinel lambs for early monitoring of the South Powys Hydatidosis Control Scheme: prevalence of Echinococcus granulosus and some other helminths.

Sentinel lambs were used to identify young Echinococcus granulosus infections in sheep, to provide an early indication of the progress of the South Powys Hydatidosis Control Scheme. Four sentinel lambs were purchased on each of 60 farms, from inside and outside the control area; they were examined when approximately six, 10 and 15 months of age. Gross examination, thin slicing of organs and histological examination of the lesions in the viscera revealed no E granulosus hydatid cysts in lambs born within the control area, whereas 25 per cent of the 15-month-old lambs from outside the area harboured E granulosus cysts (less than 1 to 2 mm in diameter). Lambs from E granulosus infected farms had significantly higher anti-E granulosus ELISA antibody titres than lambs from uninfected farms. It was concluded that within one year of beginning to treat dogs with praziquantel every six weeks the transmission of E granulosus to sheep had ceased. In contrast, this treatment did not prevent infections with Taenia hydatigena or T ovis; an examination of the 240 lambs revealed T hydatigena in 33.3 per cent of them, Tovis in 4.2 per cent, Dictyocaulus filaria in 12.1 per cent and Meullerius capillaris in 49.2 per cent.

Animals↗

The effects of in vitro phosphorylation and dephosphorylation on the thrombin-induced gelation and plasmin degradation of fibrinogen.

The alpha-chain of human fibrinogen was found to be phosphorylated in EDTA-anticoagulated whole blood when trace amounts of (gamma-32P)ATP and 7.5 mM Mg2+ ions were added. Fibrinogen was not phosphorylated if only the ATP was added. The thrombin-induced gelation of fibrinogen phosphorylated by protein kinase A, casein kinase I or II was studied spectrophotomerically. It was found that phosphorylation by protein kinase A caused the formation of thinner fibrin fibres, whereas phosphorylation by casein kinase II resulted in fibres slightly thicker than those of the control fibrinogen (equivalent to a 20% increase in the control fibrinogen concentration). Phosphorylation with casein kinase I did not significantly affect the fibrin fibre thickness. Dephosphorylation by alkaline phosphatase removed 50% of the 32P-labelled phosphate from protein kinase A-phosphorylated fibrinogen and over 90% from the casein kinase I or II-phosphorylated fibrinogens. This dephosphorylation resulted in a general increase in fibre thickness in the gelation assay in all samples, although the fibres of the phosphorylated fibrinogens remained substantially thinner than the dephosphorylated control fibrinogen. Plasmin digestion of the phosphorylated fibrinogens showed that they were more resistant to cleavage, being cleaved at only 30% to 70% of the rate of control fibrinogen and that this resistance was unaltered by dephosphorylation, in contrast to the thrombin gelation experiments.

Alkaline Phosphatase↗

Conformational changes in human fibrinogen after in vitro phosphorylation and their relation to fibrinogen behaviour.

The far-ultraviolet circular dichroism spectra of fibrinogens phosphorylated by protein kinase C or casein kinase II indicated a conformational change corresponding to an increase in ordered secondary structure. The spectra of protein kinase A- or casein kinase I-phosphorylated fibrinogens did not differ substantially from the control. Fluorescence studies indicated changes in the tertiary structure around tryptophan residues for protein kinase A- or C-phosphorylated fibrinogens, but failed to show any such change for fibrinogen phosphorylated by either of the casein kinases. This latter result was also confirmed by circular dichroism measurements in the near-ultraviolet region. The apparent increase in ordered structure was proposed as an explanation for the slower rate of plasmin degradation seen in fibrinogens after phosphorylation by protein kinase C [6], and casein kinase II, especially as both spectral changes and plasmin degradation rate were unaffected by alkaline phosphatase.

Casein Kinases↗

Plasmin digestion of human fibrinogen previously phosphorylated by protein kinase C or dephosphorylated by alkaline phosphatase in vitro.

Human fibrinogen, either untreated or previously phosphorylated by protein kinase C, was incubated with plasmin generated by streptokinase, urokinase or tissue plasminogen activator and the resulting fragments were separated by gel electrophoresis. Plasmin degradation resulted in the expected X, Y and D fragments, but the degradation rates differed. In vitro phosphorylation of fibrinogen was seen to inhibit the plasmin digestion. Treatment with alkaline phosphatase did not reverse the inhibition.

Alkaline Phosphatase↗

In vitro phosphorylation of human complement factor C3 by protein kinase A and protein kinase C. Effects on the classical and alternative pathways.

Complement factor C3, recently found to contain covalently bound phosphate, was phosphorylated in vitro by cyclic AMP-dependent protein kinase (protein kinase A) and Ca2(+)-activated, phospholipid-dependent protein kinase (protein kinase C). Both protein kinases phosphorylated the same serine residue(s) located in the C3a portion of the alpha-chain. In addition, protein kinase C phosphorylated the beta-chain to a lesser extent. Protein kinase A gave a maximal incorporation of 1 mol of phosphate/mol of C3 while that value with protein kinase C was 1.5 mol of phosphate/mol of C3. The velocity in pmol of [32P]phosphate/(min x unit kinase) was 20 times higher for protein kinase C than for protein kinase A although a 10 times lower ratio of protein kinase to C3 was used in the former case. The apparent Km for C3 was 2.6 microM when protein kinase C was used. The phosphorylated C3 was found to be more resistant to partial degradation by trypsin than unphosphorylated C3. It was also found that phosphorylation of C3 in the C3a portion of the alpha-chain inhibited both the classical and alternative complement activation pathways on an approximately stoichiometric basis.

Amino Acids↗

A survey of exposures, practices and recommendations of surgeons in the care of patients with human immunodeficiency virus.

Policy makers face a conflict between satisfying concerns of health care workers (HCW) about the occupational risk of human immunodeficiency virus (HIV) infection and ensuring adequate care for patients. This conflict is particularly severe in the field of surgery. We mailed a questionnaire on the surgical care of patients infected with HIV to 1,461 surgeons in New York City and Philadelphia, and 551 (37.7 per cent) responded. Although 1.9 per cent currently were testing all patients for HIV, 42.6 per cent of surgeons believed that all patients in their hospital should be tested. Of the surgeons who responded, 6.3 per cent refused to treat any patient infected with HIV. Less than 50 per cent recommended the use of barrier precautions on all patients in their hospital. Surgeons in New York City were significantly more likely than those in Philadelphia to favor separate facilities for HIV-infected patients. Surgeons considering themselves at higher occupational risk were more likely than those at lower risk to favor widespread testing, separate facilities and use of precautions. Surgeons reported a wide range of opinions. Their approach to the use of barrier precautions differs from the Centers for Disease Control recommendations. The patterns observed suggest that distinct policies may be appropriate for different hospitals.

Female↗

Vasopressin directly closes ATP-sensitive potassium channels evoking membrane depolarization and an increase in the free intracellular Ca2+ concentration in insulin-secreting cells.

The effects of arginine-vasopressin (AVP) (0.01-1 microM) on membrane potential, [Ca2+]i and ATP-sensitive potassium channels have been studied in the insulin-secreting cell line RINm5F. In whole cells, with an average spontaneous cellular transmembrane potential of -64 +/- 3 mV (n = 33) and an average basal [Ca2+]i of 102 +/- 6 nM (n = 40), AVP evoked: (i) membrane depolarization, (ii) voltage-dependent Ca2+ spike-potentials and (iii) a sharp rise in [Ca2+]i. Single-channel current events recorded from excised outside-out membrane patches show that AVP closes potassium channels that are also closed by tolbutamide (100 microM) and opened by diazoxide (100 microM). AVP acts on KATP channels specifically from the outside of the membrane and a soluble cytosolic messenger appears not to be involved, since there is no channel activation in cell-attached membrane patches when the peptide is added to the bath solution.

Adenosine Triphosphate↗

Phosphorylation of complement factor C3 in vivo.

Complement factor C3, the central protein of the complement system, was found to be phosphorylated both in EDTA- and heparin-anticoagulated whole blood and in coagulating blood. Complement S protein (vitronectin) was also found to be phosphorylated under these conditions. Further, purified C3 was found to be a phosphoprotein in vivo, containing 0.15 mol of alkali-labile phosphate/mol of protein. The ATP concentration in plasma was measured and found to be about 2 microM.

Adenosine Triphosphate↗

One hundred years of clinical preventive medicine in America.

The history of clinical preventive medicine has been shaped by the interactions of biomedical knowledge and sociopolitical forces. In the late nineteenth century, medical thinking shifted from the belief that diseases were caused by general bodily imbalances to the belief that diseases were caused by specific agents, and that they might be amenable to specific preventive and therapeutic approaches. During the twentieth century, preventive medicine moved from advocating a public health, community-based approach toward preventing specific diseases in individual patients. The establishment of preventive medicine as a discipline has been fostered both by recent concerns that medical care emphasizes cure, rather than care, and by efforts to reduce health care costs.

History of Medicine↗

Immunologic and hematologic responses in ponies with experimentally induced Strongylus vulgaris infection.

Immunologic and hematologic responses were examined in 4 ponies with experimentally induced Strongylus vulgaris infection and in 5 helminth-free ponies. Two ponies were inoculated with 200 larvae and 2 were inoculated with 700 larvae of S vulgaris and then were reinoculated with the same numbers of larvae 34 weeks later. Initial response of the ponies inoculated with S vulgaris was S vulgaris antigen-induced lymphocyte response that developed 1.5 to 3 weeks after inoculation and did not persist. Development of antigen-reactive lymphocytes was followed sequentially by a biphasic complement-fixing antibody response, then biphasic eosinophilia. Antibody titer to S vulgaris antigen was higher in ponies inoculated with 700 larvae, compared with that in ponies given 200 larvae of S vulgaris. Also, the second peak in antibody titer and in absolute number of eosinophils was observed earlier in ponies inoculated with 700 larvae, compared with ponies inoculated with 200 S vulgaris larvae, and subsided before or from about 24 weeks after inoculation. The prepatent period for S vulgaris infection was 24 to 25 weeks. After reinoculation with S vulgaris, a degree of increased lymphocyte responsiveness was apparent but, by 17 weeks after reinoculation, only the primary peak in the absolute number of eosinophils indicated an anamnestic response. Essentially, antibody was not detectable after reinoculation.

Animals↗

Taking care of patients--does it matter whether the physician is a woman?

Researchers have recently begun to compare male and female physicians' attitudes toward patients, medical knowledge, and practice styles. Although women start medical school with more "humanistic views," the conservative effect of medical socialization on both male and female students attenuates these differences. While some studies suggested that men are more scientifically knowledgeable, recent studies showed no significant differences in physicians' medical knowledge. Male and female physicians also had comparable diagnostic and therapeutic behavior. In the intimate world of physicians and patients, however, there were notable differences. Women physicians seemed better able to communicate sensitivity and caring to patients, which may account for the common perception that women are more caring and empathic physicians. Medical educators may wish to study more closely female physicians' communication styles to identify these behaviors and inculcate them into all physicians.

Attitude of Health Personnel↗

Pharmacy practice in the United States Army.

The current status of pharmaceutical services in the United States Army Medical Department is described. The mission of the Army Medical Department is to ensure the health of the soldier during times of peace and war. Of the 225 commissioned pharmacy officers currently on active duty, 156 are assigned to U.S. Army medical centers and community hospitals in the United States, and 29 are stationed at hospitals in Europe, Korea, Panama, and Japan. Army pharmacy officers are supported by 879 Army-trained pharmacy technicians and 319 civilian pharmacists employed by the Army. Army Medical Department hospital pharmacies provide inpatient and ambulatory-care services as well as specialized nuclear pharmacy, oncology, investigational drug, and materials development services. Pharmacy officers assigned to the Pharmacy Branch of the U.S. Army Academy of Health Sciences conduct 17-week technician training programs six times a year and provide other pharmacy courses and continuing education programs. The U.S. Army Allergen Extract Laboratory dispenses diagnostic and immunotherapy agents by mail in response to prescriptions submitted by military allergy clinics. Pharmacy officers may be deployed with field hospitals during times of combat or for extended training exercises in places such as Egypt, Grenada, and Honduras. Pharmacy officers may also be assigned to three- or four-year tours of duty in Army hospitals located in Europe. In the future, the emphasis of Army pharmacy practice will be on the expansion of clinical pharmaceutical services and the development of advanced interactive communication systems, quality assurance programs, and peer-review programs.

Allergens↗