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Biomedical subjects

C Lawrence

Publications and source records attributed to C Lawrence.

At least 37 records · Page 2Linked to original sources
PubMed2001

Coronary vasomotor and cardiac electrophysiologic effects of diadenosine polyphosphates and nonhydrolyzable analogs in the guinea pig.

Platelet activation in heart disease is important owing to the effects of platelet-derived compounds on myocardial perfusion and cardiac electrophysiology. Diadenosine polyphosphates are secreted from platelets and present in the myocardium, but their electrophysiologic and vasomotor effects are incompletely understood. We used isolated guinea-pig hearts to study the effects of diadenosine triphosphate (Ap3A), tetraphosphate (Ap4A), pentaphosphate (Ap5A), and hexaphosphate (Ap6A) (10 pM-0.1 mM), comparing their actions to those of adenosine, adenosine triphosphate, and non-hydrolyzable Ap4A and Ap5A analogs. Diadenosine polyphosphates (0.1 nM-0.1 microM) transiently reduced coronary perfusion pressure, which recovered during the continued presence of the compounds. At concentrations greater than 0.1 microM effects were maximal and sustained (perfusion pressure decreased from 36.5+/-3.4 to 18.6+/-2.5 mm Hg, p < 0.001, with 1 microM Ap4A). The changes in action potential duration and refractory period developed slowly but were maintained (0.1 nM-1 microM). With 1 nM Ap4A, action potential duration increased from 170.6+/-2.6 to 187.3+/-3.8 ms, p < 0.05, and refractory period increased from 138.5+/-1.6 to 147.9+/-2.0 ms, p < 0.05. Ap4A and its analog reduced QRS duration (from 24.7+/-1.1 to 13.9+/-1.6 ms with 1 microM Ap4A, p < 0.05). P2-purinergic (adenosine triphosphate) receptor antagonism (suramin) reduced perfusion pressure but was without electrophysiologic effect. Other changes in coronary perfusion pressure and electrophysiologic variables associated with Ap4A were not seen in the presence of suramin. P1-(adenosine) antagonism (8-[p-sulfophenyl]theophylline) attenuated the electrophysiologic effects only. Diadenosine polyphosphates have potent cardiac electrophysiologic and coronary vasomotor effects via purinergic receptors, suggesting an important role during platelet activation in acute coronary syndromes.

Action Potentials↗
PubMed2001

Ganglion of the distal interphalangeal joint (myxoid cyst): therapy by identification and repair of the leak of joint fluid.

BACKGROUND: Digital myxoid cysts are a relatively common pathology in the skin, representing a ganglion of the adjacent distal interphalangeal joint. Success of treatment is largely proportional to the destructiveness of the therapy and postoperative morbidity. We studied an effective, minimally traumatic surgical treatment in which tissue is not removed and morbidity is low. DESIGN: Open, nonrandomized trial of therapy. Methylene blue dye was injected into the distal interphalangeal joint. A skin flap was designed around the cyst and raised to identify the dye-filled communication between joint and cyst. The communication was sutured and the flap was replaced with no tissue excision. SETTING: Two university dermatology departments. PATIENTS: Fifty-four subjects with 47 cysts involving fingers or thumbs and 7 involving toes. Previous therapies in 37 patients had resulted in relapse. MAIN OUTCOME MEASURES: Clinical assessment at 2 and 8 months. RESULTS: We treated 34 women and 20 men (mean age, 60.4 years; range, 45-83 years). Communication between cyst and joint was identified by means of methylene blue injection in 48 patients (89%). At 8 months, 48 patients remained cured with no visible scarring. Of these, nail dystrophy associated with the cyst preoperatively (n = 35) resolved in all but 1 patient (97%). Six patients had relapses (5 within 4 months). Of these, 3 were on the toes. Cure rate on toes was 4 of 7 (57%) and on fingers, 44 of 47 (94%). In 2 patients, pain persisted for 4 months and then resolved. Limitation of joint mobility resolved after 2 months in 1 subject. CONCLUSIONS: Ligature of myxoid cyst origin at the joint capsule is an effective treatment and does not require excision. Myxoid cysts on toes are more likely to relapse than those on fingers.

Aged↗
PubMed2000

Effects of mild night chilling on respiration of expanding cotton leaves.

Utilizing expanding leaves of cotton (Gossypium hirsutum L. cv. Coker 312), the hypothesis that suboptimal night temperatures above those for putative phase transitions of mitochondrial lipids caused greater substrate control of night respiration and increased the control that respiration exerted on ATP-dependent metabolism was tested. Night respiratory CO(2) evolution rates for 5-7-day-old leaves growing at 30/19 degrees (day/night) nearly equaled those of leaves exposed to 28 degrees C nights, while leaves exposed to 15 degrees C nights had rates that were 42% of those at 28 degrees C. No restriction of respiration by carbohydrate supply was detected for leaves grown at either cool night temperature or when warm-grown plants were transferred to cool night conditions. Pyruvate utilization was more sensitive to mild chilling than glycolysis. Growth at 30/19 or 30/15 degrees C resulted in higher nocturnal ATP:ADP and energy charge for expanding leaves than growth at 30/28 degrees C, suggesting a lessening of respiratory control of ATP-dependent metabolism with long-term night chilling. However, cool night exposure resulted in reductions in total phosphorylated adenylates, and the low ATP content, most notably occurring during 15 degrees C nights, may have restricted some metabolic activity. The cause of these low ATP levels and their possible effects on cotton metabolism during chilling remain to be elucidated.

Journal Article↗
PubMed2000

Hemoglobin C in transgenic mice: effect of HbC expression from founders to full mouse globin knockouts.

When present in the homozygous form, hemoglobin C (HbC, CC disease) increases red cell density, a feature that is the major factor underlying the pathology in patients with SC disease (Fabry et al., JCI 70, 1315, 1982). The basis for the increased red cell density has not yet been fully defined. We have generated a HbC mouse in which the most successful founder expresses 56% human alpha and 34% human beta(C). We introduced knockouts (KO) of mouse alpha- and beta-globins in various combinations. In contrast to many KO mice, all partial KOs have normal MCH. Full KOs that express exclusively HbC and no mouse globins have minimally reduced MCH (13. 7 +/- 0.3 pg/cell vs 14.5 +/- 1.0 for C57BL/6) and a ratio of beta- to alpha-globin chains of 0.88 determined by chain synthesis; hence, these mice are not thalassemic. Mice with beta(C) > 30% have increased MCHC, dense reticulocytes, and increased K:Cl cotransport. Red cell morphology studied by SEM is strikingly similar to that of human CC cells with bizarre folded cells. We conclude that red cells of these mice have many properties that closely parallel the pathology of human disease in which HbC is the major determinant of pathogenesis. These studies also establish the existence of the interactions with other gene products that are necessary for pleiotropic effects (red cell dehydration, elevated K:Cl cotransport, morphological changes) that are also present in these transgenic mice, validating their usefulness in the analysis of pathophysiological events induced by HbC in red cells.

Alanine Transaminase↗
PubMed2000

Antibody to transforming growth factor-beta ameliorates tubular apoptosis in unilateral ureteral obstruction.

BACKGROUND: Unilateral ureteral obstruction (UUO) is characterized by progressive renal atrophy, renal interstitial fibrosis, an increase in renal transforming growth factor-beta (TGF-beta), and renal tubular apoptosis. The present study was undertaken to determine the effect of a monoclonal antibody to TGF-beta (1D11) in UUO. METHODS: Mechanical stretch was applied to tubular epithelial cells (NRK-52E) by a computer-assisted system. Three doses of 1D11 (either 0.5, 2, or 4 mg/rat) were administered to rats one day prior to UUO and every two days thereafter, and kidneys were harvested at day 13. Fibrosis was assessed by measuring tissue hydroxyproline and mRNA for collagen and fibronectin. Apoptosis was assessed with the terminal deoxy transferase uridine triphosphate nick end-labeling assay. TGF-beta levels were determined by bioassay. Western blot and immunostaining were used to identify proliferating cell nuclear antigen (PCNA), p53, bcl-2, and inducible nitric oxide synthase (iNOS). RESULTS: Stretch significantly induced apoptosis in NRK-52E cells, which was accompanied by an increased release of TGF-beta; 1D11 (10 microg/mL) totally inhibited stretch-induced apoptosis. Control obstructed kidney contained 20-fold higher TGF-beta as compared with its unobstructed kidney; 1D11 neutralized tissue TGF-beta of the obstructed kidney. Control obstructed kidney exhibited significantly more fibrosis and tubular apoptosis than its unobstructed counterpart, which was blunted by 1D11. In contrast, 1D11 significantly increased tubular proliferation. p53 immunostaining was localized to renal tubular nuclei of control obstructed kidney and was diminished by 1D11. In contrast, bcl-2 was up-regulated in the 1D11-treated obstructed kidney. Total NOS activity and iNOS activity of the obstructed kidney were increased by 1D11 treatment. CONCLUSION: The present study strongly suggests that an antibody to TGF-beta is a promising agent to prevent renal tubular fibrosis and apoptosis in UUO.

Animals↗
PubMed2000

Associations between primary appraisals and life-events while controlling for depression.

OBJECTIVES: The main objective of this paper was to explore the associations between life-events and primary appraisals (threat, challenge and loss) controlling for depression. It was predicted that specific associations between life-events and primary appraisals would remain once depression had been partialled. A subgoal of this paper was to develop a content analytic coding frame for student life-events. DESIGN: This study was a retrospective survey in which participants provided accounts of recent stressful encounters, and completed indices of primary appraisals and depression. METHOD: The participants were 979 undergraduates who provided descriptions of life-events. A subsample of 391 provided additional information on primary appraisals and depression. The primary outcomes were the partial correlations between life-events and primary appraisals. RESULTS: There were significant associations between life-events and primary appraisals above and beyond variance explained by depression. Results also indicated that the definition of loss appraisals could be extended to include events that were related to anticipated future loss, especially if the event was also perceived as threatening. Also certain self-defined negative life-events were appraised as positive. Life-events were shown to vary systematically as a function of external constraints (e.g. stage of the academic year). CONCLUSIONS: A variety of events were associated with loss appraisals and this may have implications for risk factors in depression.

Adaptation, Psychological↗
PubMed1999

Myocarditis and cardiomyopathy associated with clozapine.

BACKGROUND: Clozapine is effective for resistant schizophrenia. After two sudden deaths in physically well young men soon after starting clozapine, we investigated the cardiovascular complications for this drug. METHODS: From January, 1993, to March, 1999, 8000 patients started clozapine treatment in Australia, and were registered with a mandatory monitoring service. We identified cases of myocarditis and cardiomyopathy from voluntary reports to the Australian Adverse Drug Reaction Committee and sought details of the relevant diagnostic studies, necropsies that had been done in suspicious cases, or both. FINDINGS: 23 cases (20 men, three women, mean age 36 years [SD 9]) were identified: 15 of myocarditis and eight of cardiomyopathy associated with clozapine treatment. Six patients died. All cases of myocarditis (five deaths) occurred within 3 weeks of starting clozapine. Cardiomyopathy (one death) was diagnosed up to 36 months after clozapine was started. Necropsy results showed mainly eosinophilic infiltrates with myocytolysis, consistent with an acute drug reaction. INTERPRETATION: Clozapine therapy may be associated with potentially fatal myocarditis and cardiomyopathy in physically healthy young adults with schizophrenia.

Adolescent↗
PubMed1999

Is there a rationale for rationing chronic dialysis? A hospital based cohort study of factors affecting survival and morbidity.

OBJECTIVES: To determine factors influencing survival and need for hospitalisation in patients needing dialysis, and to define the potential basis for rationing access to renal replacement therapy. DESIGN: Hospital based cohort study of all patients starting dialysis over a 4 year recruitment period (follow up 15-63 months). Groups were defined on the basis of age, comorbidity, functional status, and whether dialysis initiation was planned or unplanned. SETTING: Renal unit in a district general hospital, which acts as the main renal referral centre for four other such hospitals and serves a population of about 1.15 million people. SUBJECTS: 292 patients, mean age 61.3 years (18-92 years, SD 15.8), of whom 193 (66%) were male, and 59 (20%) were patients with diabetes. Dialysis initiation was planned in 163 (56%) patients and unplanned in 129 (44%). MAIN OUTCOME MEASURES: Overall survival, 1 year survival, and hospitalisation rate. RESULTS: Factors affecting survival in the Cox's proportional hazard model were Karnofsky performance score at presentation (hazard ratio 0.979, 95% confidence interval 0.972 to 0. 986), comorbidity severity score (1.240, 1.131 to 1.340), age (1.036, 1.018 to 1.054), and myeloma (2.15, 1.140 to 4.042). The Karnofsky performance score used 3 months before presentation was significant (0.970, 0.956 to 0.981), as was unplanned presentation in this model (1.796, 1.233 to 2.617). Using these factors, a high risk group of 26 patients was defined, with 19.2% 1 year survival. Denying dialysis to this group would save 3.2% of the total cost of the chronic programme but would sacrifice five long term survivors. Less rigorous definition of the high risk group would save more money but lose more long term survivors. CONCLUSIONS: Severity of comorbid conditions and functional capacity are more important than age in predicting survival and morbidity of patients on dialysis. Late referral for dialysis affects survival adversely. Denial of dialysis to patients in an extremely high risk group, defined by a new stratification based on logistic regression, would be of debatable benefit.

Activities of Daily Living↗
PubMed1999

Plasmodium falciparum: enhanced gametocyte formation in vitro in reticulocyte-rich blood.

Concentrates of late stage parasites of the gametocyte-forming clone HB-3 were mixed with blood rich in reticulocytes from anemic patients, or with normal control blood, and kept under culture conditions for 4 days. Significantly more gametocytes were always formed in the reticulocyte-rich blood than in the control. This was true whether the anemic blood supported a larger asexual parasitemia than the control, or a lower one, or the same and without regard to the cause of the anemia. Gametocytes as a percentage of asexual forms were up to 10 times higher in reticulocyte-rich blood than in normal blood.

Anemia↗
PubMed1999

A Na+-activated K+ current (IK,Na) is present in guinea-pig but not rat ventricular myocytes.

The effects of removing extracellular Ca2+ and Mg2+ on the membrane potential, membrane current and intracellular Na+ activity (aiNa) were investigated in guinea-pig and rat ventricular myocytes. Membrane potential was recorded with a patch pipette and whole-cell membrane currents using a single-electrode voltage clamp. Both guinea-pig and rat cells depolarize when the bathing Ca2+ and Mg2+ are removed and the steady-state aiNa increases rapidly from a resting value of 6.4+/- 0.6 mM to 33+/-3.8 mM in guinea-pig (n=9) and from 8.9+/-0.8 mM to 29.3+/-3.0 mM (n=5) in rat ventricular myocytes. Guinea-pig myocytes partially repolarized when, in addition to removal of the bathing Ca2+ and Mg2+, K+ was also removed, however rat cells remained depolarized. A large diltiazem-sensitive inward current was recorded in guinea-pig and rat myocytes, voltage-clamped at -20 mV, when the bathing divalent cations were removed. When the bathing K+ was removed after Ca2+ and Mg2+ depletion, a large outward K+ current developed in guinea-pig, but not in rat myocytes. This current had a reversal potential of -80+/-0.7 mV and was not inhibited by high Mg2+ or glybenclamide indicating that it is not due to activation of non-selective cation or adenosine triphosphate (ATP)-sensitive K channels. The current was not activated when Li+ replaced the bathing Na+ and was blocked by R-56865, suggesting that it was due to the activation of KNa channels.

Animals↗