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Biomedical subjects

W Campbell

Publications and source records attributed to W Campbell.

At least 19 recordsLinked to original sources

Crystallization and preliminary crystallographic studies of the FAD domain of corn NADH: nitrate reductase.

Crystals of the flavin domain of corn nitrate reductase expressed in Escherichia coli have been obtained at room temperature, using sodium citrate as precipitant. The crystals diffract to at least 2.5 A resolution at a synchrotron radiation source. Precession photographs show that they belong to the rhombohedral space group R3 with unit cell dimensions a = b = 145.4 A, c = 47.5 A, alpha = beta = 90 degrees and gamma = 120 degrees. There is one subunit per asymmetric unit which gives a packing density of 3.2 A3/Da, indicating a high solvent content in these crystals.

Crystallization

The use of hepatobiliary scintigraphy in patients with acalculous biliary colic.

Twelve patients with biliary colic had no evidence of gallstones but underwent cholecystokinin-augmented hepatobiliary scintigraphy that revealed gallbladder ejection fractions of less than 35%. All 12 patients underwent cholecystectomy. Biliary colic was relieved in all patients at a mean postoperative follow-up of 2.5 years. The biliary colic in these patients was probably caused by abnormal gallbladder emptying, itself apparently produced by either cystic duct obstruction or abnormal motility. Biliary abnormality was seen at operation in most patients, and all patients had abnormalities of the gallbladder or cystic duct seen grossly or histologically. These abnormalities included cystic duct stenosis or adhesions, chronic inflammation, and cholesterolosis.

Adult

Antisense sequences of antigenic peptides are found in MHC class II molecules.

The sequence of the well known antigenic peptide OVA 323-339 as well as other peptides containing reiterative motifs of the core region essential for binding to Class II MHC molecules was compared for homology with the DNA derived antisense peptide sequences corresponding to the alpha chain of the mouse IAd molecule. Homology was obtained within the sequence found in the transmembrane region of the molecule. Increased binding of the peptides containing the reiterative motifs based on the OVA 323-339 sequence may be due to the increased number of contact sites on IAd molecules which were identified as being complementary in a sense-antisense manner.

Amino Acid Sequence

An arginine carboxypeptidase generated during coagulation is diminished or absent in patients with rheumatoid arthritis.

A novel arginine carboxypeptidase that is generated during blood coagulation is diminished in sera obtained from patients with rheumatoid arthritis. The enzyme, which is unrelated to carboxypeptidase N, is more effective than lysine in removing terminal arginine from small synthetic substrates and may function in vivo in the removal of terminal arginine from inflammatory peptides such as C3a and C5a. Either diminished levels of this enzyme or an inability to generate it may be an important consideration in the mechanisms involved in the local inflammation that is observed in patients with rheumatoid arthritis.

Arthritis, Rheumatoid

An arginine specific carboxypeptidase generated in blood during coagulation or inflammation which is unrelated to carboxypeptidase N or its subunits.

An unstable carboxypeptidase N or B like enzyme is generated as a result of coagulation. This enzyme is derived from some plasma component (s) and not from blood cells or platelets. Furthermore, the activity generated is specific for arginine substrates insofar as small synthetic substrates are concerned. The enzyme is unrelated to CPN or any of its subunits or subunit fragments. This transient carboxypeptidase may be involved in the processing and/or scheduling of different functions of bioactive peptides generated during inflammation.

Arginine

120 hours simultaneous infusion of cisplatin and fluorouracil in metastatic breast cancer.

Thirty-six patients with metastatic breast cancer, 23 with documented progression of the disease after first-line chemotherapy (CAF or CMF) and 13 without prior chemotherapy, were treated with a simultaneous 120-h infusion of cisplatin (CDDP) and 5-fluorouracil (5-FU). Objective response was demonstrated in 19 patients (52.7%), stable disease in 7 patients (19.4%) and progression of the disease in 10 patients (27.7%). Similar response rate was observed according to tumor site (soft tissues, 50%; bone, 52%; lung, 63%; liver, 55%; and pleura and peritoneum, 42%) and previous treatment (previous chemotherapy, 48%; previously untreated, 61%). Median duration of response was 8 months. Toxicity was characterized by stomatitis and myelodepression and required dose adjustments in 30% of patients. CDDP and 5-FU infusion deserve further investigation because it appeared to have substantial activity in this preliminary study in metastatic breast cancer.

Adult

A randomized clinical trial of haloperidol decanoate and fluphenazine decanoate in the outpatient treatment of schizophrenia.

We carried out an 8-month double-blind clinical trial comparing haloperidol decanoate with fluphenazine decanoate in the maintenance treatment of 72 schizophrenic outpatients. A parallel-groups design was used with stratification by sex and injection interval (2, 3, or 4 weeks). The initial injection interval was based on pretrial maintenance treatment with fluphenazine esters. The dosage equivalency of haloperidol decanoate (1.5 cc or 75 mg) to fluphenazine decanoate (1 cc or 25 mg) used was 3:1. This remained approximately the same throughout a 2-month titration period with a flexible dose regimen, and a further 6-month period with a fixed dose regimen. No statistically significant differences in therapeutic effect were found between the drugs. Both drugs had a similar profile for drug-induced parkinsonism, but there was a trend for differences in masking tardive dyskinesia. Haloperidol and prolactin plasma concentrations were well correlated with dosage, with the exception of haloperidol concentrations in patients receiving injections at 2-week intervals.

Adolescent

Constriction of the fetal ductus arteriosus after administration of indomethacin to the pregnant ewe.

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in the fetal pulmonary to systemic arterial mean blood pressure difference across the ductus arteriosus rising significantly, presumably secondary to constriction of the ductus arteriosus. The pressure difference was due to pulmonary arterial hypertension, and not due to a fall in systemic arterial mean blood pressure. Fetal arterial blood gas tensions and pH values were normal throughout. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of PGE1 into the fetal inferior vena cava. Indomethacin was present in fetal blood, and maternal plasma prostaglandin levels were suppressed. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus and fetal pulmonary arterial hypertension which, if severe, may cause rapid fetal death. It is possible that this mechanism may be one cause of persistent pulmonary hypertension or tricuspid insufficiency or both in the newborn infant.

Animals

Autonomic dysfunction in women with mitral valve prolapse syndrome.

Autonomic cardiovascular regulation was evaluated in 35 women, 19 with mitral valve prolapse and 16 healthy controls. Heart rate responses to the diving reflex and to phenylephrine infusion were diminished in patients. Noninvasive measures of cardiac output, heart rate, blood pressure, forearm flow and leg volume during lower body negative pressure (LBNP) showed that patients had less lower extremity pooling of blood and had lower forearm conductance. Blood pressures during LBNP rose or remained unchanged despite decreases in cardiac output of 20--25%. These data indicate that mitral valve prolapse patients have an increased venous and arterial vasoconstrictor activity. Cardiac output at rest and echocardiographic indices of contractility were normal. Patients with a history of significant ventricular arrhythmias had higher heart rates and lower forward stroke volumes than the other patients or controls. The combined data demonstrate autonomic dysfunction in women with the mitral valve prolapse syndrome and suggest decreased parasympathetic, increased alpha- and normal beta-adrenergic tone and responsiveness.

Adult

The pharmacokinetics of slow-release procainamide.

Procainamide was given to 20 patients with normal renal function as an i.v. bolus of 500 mg followed by 1.0 or 1.5 g eight-hourly by mouth in the form of a slow release preparation (Durules). 97.6 +/- 27.1 (SD)% of the oral procainamide was absorbed, the absorption half life being 1.54 h. The elimination half life following the oral formulation was 6.0 +/- 0.8 h, compared to a mean of 3.4 +/- 0.4 h following i.v. administration. Elimination half life following i.v. administration was slightly related to acetylator status, being 2.75 +/- 0.9 h in fast acetylators, and 4.4 +/- 2.4 h in slow acetylators. This dependence on acetylator status was not seen in half life following oral administration. Total body clearance, steady state plasma procainamide and N-acetylprocainamide were not significantly dependent on acetylator status, although a few patients who are slow acetylators had unexpectedly low clearance and high steady state procainamide concentrations when given the higher dose.

Biological Availability

Role of cardiac output in the pressor responses to graded muscle ischemia in man.

Ten men repeatedly performed leg exercise (100-150 W) for 7 min with 30-min recovery periods interspersed. Both legs were made ischemic by total occlusion (OCCL), first for 3 min immediately after exercise and second for 30 s before exercise ended and 3 min into recovery. In addition legs were occluded for 3 min at rest (seated). OCCL at rest increased mean arterial pressure (MAP) by 9 Torr but did not affect cardiac output (CO) or heart rate (HR). OCCL at the end of exercise significantly raised MAP and HR above control values during 3-min recovery but CO was unaffected. OCCL 30 s before the end of exercise further increased MAP and HR significantly during recovery; MAP, CO, and HR were significantly increased above control values (CO by 2.1 1-min-1) during the 3rd min of recovery. We conclude that a strong reflex from ischemic legs maintains normal or elevated CO during leg OCCL. Thus CO was too high relative to total vascular conductance so that MAP was elevated.

Blood Pressure