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Biomedical subjects

C Welch

Publications and source records attributed to C Welch.

At least 37 records · Page 2Linked to original sources

Evidence to suggest nitric oxide is an interstitial regulator of Leydig cell steroidogenesis.

Recent studies have suggested that nitric oxide (NO) may function as both an intracellular and intercellular signal that affects neural and immunological activity, vascular tone, platelet adhesion, and production of some hormones. Arginine analogs such as NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine methyl ester (L-NAME) act to inhibit the intracellular formation of NO and have been used to study the effects of decreased NO formation on physiological systems. A single in vivo study has suggested that a similar analog, NG-nitro-L-arginine, increases serum testosterone (T), but the organ site and mechanism of action were not investigated. The present study was performed to investigate the effects of NO synthase inhibitors on Leydig cell function. L-NMMA and L-NAME, but not the inactive enantiomer (D-NMMA), increased both basal and human chorionic gonadotropin (hCG)-stimulated T production while decreasing guanosine 3':5'-cyclic monophosphate (cGMP). There was no effect on either adenosine 3':5'-cyclic monophosphate (cAMP) accumulation or specific hCG binding. These results suggest that NO formation, which is inhibited by L-NMMA and L-NAME, is important in the regulation of Leydig cell T production by interstitial cells of the testis, and that changes in cGMP levels might be involved in this process.

Animals↗

New insights into atherosclerosis from studies with mouse models.

Atherosclerosis is a disease of the large arteries that is the cause of heart disease and stroke. It is a highly complex disorder with multiple genetic and environmental influences. The mouse model has proved very useful for studying atherosclerosis because genetic analysis and planned genetic modification are feasible in this organism. In this brief review, some recent findings are summarized and future prospects using mouse models to study atherosclerosis-related traits are discussed.

Animals↗

Identification of staphylococcal enterotoxin B sequences important for induction of lymphocyte proliferation by using synthetic peptide fragments of the toxin.

A series of 13 synthetic peptides, approximately 30 amino acids each, which spanned the entire sequence of staphylococcal enterotoxin B (SEB) were tested to evaluate their effects on T-cell proliferation in a culture system containing elutriated human peripheral blood lymphocytes incubated with a specific ratio of mononuclear cells. Four peptide regions were found to inhibit SEB-induced proliferation; they included sequences 1 to 30 (previously thought to be involved in major histocompatibility complex class II binding), 61 to 92 (sequences which relate to the T-cell receptor site), 93 to 112 (a linear sequence corresponding to the cysteine loop), and 130 to 160 (containing a highly conserved sequence, KKKVTAQEL). Antisera raised to this last peptide were capable of neutralizing SEB-induced proliferation. Antisera raised against the peptides which overlapped this sequence also were somewhat inhibitory. Neutralizing antisera were not produced from any other peptide sequence tested. To determine if any of these effects were nonspecific with regard to SEB-induced proliferation, the peptides were tested for inhibition of phorbol dibutyryl ester-induced proliferation, and only the sequence 93 to 112 (corresponding to the cysteinyl loop region) was consistently inhibitory (40%). Of the regions which displayed inhibition of SEB-induced proliferation, the peptide 130 to 160 inhibited binding of 125I-SEB to lymphocytes. These data suggest that the residues containing and surrounding the sequence KKKVTAQEL may be critical in the SEB-induced proliferation and may be useful for developing neutralizing antisera to SEB.

Amino Acid Sequence↗

Antiproliferative effect of the garlic compound S-allyl cysteine on human neuroblastoma cells in vitro.

A variety of compounds derived from garlic bulbs have been shown in animal systems to possess anticancer properties. However, little information is available regarding the effectiveness of garlic in the prevention or treatment of human cancers. In the current study, we have assessed the ability of S-allyl cysteine (SAC), a derivative of aged garlic extract, to affect the proliferation and differentiation of LA-N-5 human neuroblastoma cells in vitro. Time-and dose-dependent inhibition of cell grow was observed in cultures treated with SAC for at least 2 days, with a half-maximal response at approximately 600 micrograms/ml. SAC treatment was unable to induce differentiation in neuroblastoma cells as assessed by morphological, biochemical and molecular markers. In addition, SAC was unable to potentiate the effects of retinoic acid and 8-bromo-cyclic AMP, agents known to promote differentiation of LA-N-5 cells. Our results indicate that SAC can inhibit human neuroblastoma cell growth in vitro. However, the apparent inability of this compound to induce differentiation may limit its therapeutic potential.

Acetylcholinesterase↗

Electroconvulsive therapy treatment of depression in a patient with adult GM2 gangliosidosis.

Adult GM2 gangliosidosis is a rare disorder that often presents with both neurological and psychiatric syndromes. Effective treatment of the psychotic and affective symptoms associated with this disorder has been complicated by poor treatment response and the concern that many psychotropic agents may worsen the underlying gangliosidosis. We report the successful use of electroconvulsive therapy for treatment of severe depression in a young man with adult GM2 gangliosidosis.

Adult↗

Evidence for the involvement of a K+ channel in isosmotic cell shrinking in vestibular dark cells.

Cell volume changes were measured in dark cells. Isosmotic addition of 21.4 mM K+, Rb+, Cs+, or NH4+ to a control solution containing 3.6 mM K+ caused piretanide-sensitive cell swelling (initial rate for K+, 0.100 +/- 0.005 microns/s; n = 119), suggesting dependence on the Na(+)-Cl(-)-K+ cotransporter. Subsequent isosmotic removal of 21.4 mM K+ caused piretanide-insensitive cell shrinking (initial rate, -0.104 +/- 0.005 microns/s; n = 119), which was inhibited by barium, lidocaine, quinidine, quinine, verapamil, and 4-aminopyridine but not tetraethylammonium (TEA) or glibenclamide, suggesting the involvement of K+ channel(s). Barium, lidocaine, quinine, quinidine, and 4-aminopyridine caused cell swelling in control solution (initial rate for barium, 0.011 +/- 0.004 microns/s; n = 6), suggesting that the K+ channel is also involved in efflux under control conditions. Cell shrinking was slowed by 21.4 mM extracellular K+, Rb+, or Cs+ but unaffected by Na+, Li+, TEA+, or NH4+ (all in the presence of piretanide and compared with N-methyl-D-glucamine), supporting the notion that the efflux mechanism is permeable to and/or inhibited by K+, Rb+, and Cs+. Cell shrinking was slowed by the presumed replacement of intracellular K+ by Cs+ but not by Rb+. Circumstantial evidence suggests that this putative K+ channel is present in the basolateral membrane. The physiological relevance of such a K+ channel might encompass regulatory volume decrease during K+ secretion.

Animals↗

Development and evaluation of a kinetic diacetyl monoxime method for urine urea.

A kinetic assay for urine urea which employs the reaction with diacetylmonoxime at 37 degrees C and undiluted urine was developed. Reaction conditions were optimized using the Monarch centrifugal analyser to produce an assay with the linearity to 450 mmol/L urea, and CVs of 2.3% and 2.5% within-batch and 4.6% and 3.3% between-batch at urea concentrations of 75.9 and 162.7 mmol/L, respectively; recoveries of 98.5% to 99.5% were obtained with the addition of the equivalent of 95 and 190 mmol/L urea. Comparisons were made with one urine urea method employing diacetylmonoxime with dialysis and two enzymatic methods which all involve a sample pre-dilution stage. The urine samples used for the method comparisons did not contain preservatives. However, a range of urine preservatives and a selection of possible interfering metabolites were shown to have no significant effect on the recovery of urea in the assay.

Ammonia↗

An NADH-linked luciferase assay for glycogen: the preparation of glycogen-free, viable human eccrine sweat glands.

A glycogen assay based on bacterial NADH luciferase is described. It is free of tissue interference. The detection limit is 0.12 nmol glycogen, and the coefficient of variation is 5.5%. A method of depleting human eccrine sweat glands while retaining their viability is described. This depends on their incubation in 10(-5) M acetylcholine and 1 mM pyruvate. This method may be applicable to other tissues. The evidence for the viability of glycogen-depleted human eccrine sweat glands is reported and includes tissue contents of ATP and the rates of oxidation of glucose, pyruvate, beta-hydroxybutyrate, and palmitate.

Adenosine Triphosphate↗

Tarsorrhaphy for corneal disease in patients with rheumatoid arthritis.

We report two patients with keratoconjunctivitis sicca and rheumatoid arthritis whose corneal surfaces regained their integrity following tarsorrhaphy when conservative therapeutic measures were unsuccessful. We suggest that tarsorrhaphy be considered early in the course of the disease in such patients when other measures have failed to arrest progressive thinning of the cornea.

Aged↗

The effects of electroconvulsive therapy on serial electrocardiograms and serum cardiac enzyme values. A prospective study of depressed hospitalized inpatients.

Electroconvulsive therapy (ECT) is an effective, safe, and controversial treatment of severe depression. In order to further evaluate its safety, the effect of ECT on serial electrocardiograms and serum cardiac enzyme values was studied prospectively in 29 patients. Neither persistent electrocardiographic changes nor elevations in creatine phosphokinase or serum glutamic oxalaminase transaminase levels were observed following 85 treatments. Twenty-four percent of our patients had stable, preexisting cardiovascular disease, which included conduction system disease, recent myocardial infarction, and depressed ventricular function. Electroconvulsive therapy was well tolerated by all of these patients. The proposed mechanisms for transient or persistent electrocardiographic changes and cardiovascular complications of ECT are reviewed.

Adult↗

Obstructive and perforative colonic carcinoma: patterns of failure.

Carcinoma of the colon complicated by obstruction or perforation has been recognized as having a poorer prognosis than tumors without obstruction or perforation. To clarify the natural history, failure patterns, and implications for adjuvant treatment after resection with curative intent, a review of the recent Massachusetts General Hospital (MGH) experience was undertaken. From 1970 to 1977, 77 patients with obstructive colonic carcinoma and 34 patients with localized perforation at the tumor site were identified and compared with a control group of 400 patients without obstruction or perforation undergoing curative resection. All patients were observed for a minimum of five years or until the patient's death. The actuarial five-year survival and disease-free survival rates in patients with obstruction was 31% and 44%, respectively, in contrast to 59% and 75% in control patients. For patients with localized perforation, the five-year actuarial survival and disease-free survival rates were 44% and 35%, respectively. Of the 77 patients with obstructing tumors, 32 patients (42%) developed local failure--nine with local failure only and 23 patients with local failure and distant metastases. Thirty-four patients (44%) developed distant metastases. Fifteen (44%) patients of 34 with perforative colonic carcinoma had local failure. Distant metastases occurred in 15 patients (44%). The incidence of local failure and distant metastases in the control group was 14% and 21%, respectively. The rate of local failure and distant metastases increased with stage and was generally higher stage for stage than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Local failure following curative resection of colonic adenocarcinoma.

A retrospective review of the medical records of 533 patients undergoing resection with curative intent of large bowel above the peritoneal reflection was undertaken to identify subsets of patients at high risk for local failure. The overall local failure rate was 102/533 (19%) with 32/102 patients having local failure only and 70/102 patients having concurrent local failure and distant metastases. Pathological confirmation of local failure was obtained in 79% of the cases and by surgical exploration in 75%. Overall local failure rates increased with advancing stage of disease. Tumors staged B3, C2 and C3 all had local failure rates in excess of 30%, whereas for Stage A, B1, B2 and C1 lesions, the incidence of local failure was less than 4%. Stage B2 tumors arising in high and low sigmoid and splenic and hepatic flexure had a moderate incidence of local failure (21%) compared to low incidence (5%) at all other sites. The majority of local and regional failures 84/102 (82%) occurred in tumor bed and adjacent soft tissues whereas only 18/102 (18%) local failures occurred in regional nodal groups. The overall local failure rate increased from 27% with one lymph node involved to 50% with greater than 5 lymph nodes involved. Patients with Stage B3, C2 and C3 colon tumors at all sites and selected B2 tumors have a high rate of local failure after surgical resection. The value of postoperative radiotherapy should be formally studied in these patients.

Adenocarcinoma↗