Search PubMed⌕ Search

Biomedical subjects

T Cook

Publications and source records attributed to T Cook.

At least 109 records · Page 6Linked to original sources
PubMed1990

Restricted V-segment usage in T-cell receptors from cytotoxic T lymphocytes specific for a major epitope of lymphocytic choriomeningitis virus.

Cytotoxic T lymphocytes (CTL) play an important role in recovery from a number of viral infections. They are also implicated in virus-induced immunopathology as best demonstrated in lymphocytic choriomeningitis virus (LCMV) infection of adult immunocompetent mice. In the present study, the structure of the T-cell receptor (TCR) in LCMV-specific CTL in C57BL/6 (B6) mice was investigated. Spleen T cells obtained from LCMV-infected mice were cultured in vitro with virus-infected stimulator cells and then stained with anti-TCR V beta antibodies. A skewing of V beta usage was noticeable in T cells enriched for their reactivity to LCMV, suggesting that particular V segments are important for the recognition of LCMV T-cell epitopes in B6 mice. To gain more detailed information on the structure of the TCR specific for LCMV epitopes, we studied CTL clones. It has been shown that approximately 90% of LCMV-reactive CTL clones generated in H-2b mice are specific for a short peptide fragment of the LCMV glycoprotein, residues 278 to 286, recognized in the context of the class I major histocompatibility complex molecule, Db. Four CTL clones possessing the specificity were randomly selected from a collection of clones, and their TCR genes were isolated by cDNA cloning or by the anchored polymerase chain reaction. All four clones were found to use V alpha gene segments belonging to the V alpha 4 subfamily. By RNA blot analysis, two more clones with the same specificity were also shown to express the V alpha 4 mRNA. In contrast, three different V beta gene segments were used among the four clones examined. J beta 2.1 was used by three of the clones. Although amino acid sequences in the V(D)J junctional regions were dissimilar, aspartic acid was found in the V alpha J alpha and/or V beta D beta J beta junctions of all four of these clones, suggesting that this residue is involved in binding the LCMV fragment. Restricted usage of V alpha and possibly J beta segments in the CTL response to a major T-cell epitope of LCMV raises the possibility that immunopathology in LCMV infection can be treated with antibodies directed against such TCR segments. Thus, similar analysis of the TCR in other virus infections is warranted and may lead to therapeutic strategies for immunopathology due to virus infections.

Amino Acid Sequence↗
PubMed1989

Comparison of low-dose simvastatin and gemfibrozil in the treatment of elevated plasma cholesterol. A multicenter study. The Simvastatin Study Group.

A 12-week, randomized, double-blind, multicenter study was undertaken to compare the efficacy, tolerability, and safety of simvastatin and gemfibrozil in 290 patients with primary hypercholesterolemia. Patients in stratum I (initial low-density lipoprotein cholesterol level less than 195 mg/dl) received simvastatin 5 to 10 mg once every afternoon; patients in stratum II (initial low-density lipoprotein cholesterol level at least 195 mg/dl) received 10 to 20 mg once every afternoon. Gemfibrozil was given in a constant dosage of 600 mg twice daily in both strata. Simvastatin reduced low-density lipoprotein cholesterol levels by 26 and 34 percent in strata I and II, respectively. The corresponding reductions brought about by gemfibrozil were 18 and 17 percent. High-density lipoprotein cholesterol was increased by 7 and 9 percent by simvastatin and by 17 and 16 percent by gemfibrozil in strata I and II, respectively. Ratios of low-density to high-density lipoprotein cholesterol were reduced by approximately 25 percent by simvastatin 5 to 10 mg once every afternoon and gemfibrozil 600 mg twice daily, but were reduced by 37 percent by simvastatin 10 to 20 mg once every afternoon. Both drugs reduced plasma triglyceride levels, but gemfibrozil was much more effective. The short-term tolerability and safety of both drugs appeared to be good during the 12-week study. The results suggest that both drugs have useful but distinctly different lipid-modifying properties.

Anticholesteremic Agents↗
PubMed1989

Congenital mesoblastic nephroma, renin production, and hypertension.

Between 1964 and 1987, 12 patients with mesoblastic nephroma were treated. The BP was measured preoperatively in five patients, four of whom were hypertensive. Following nephrectomy, the BP returned to normal. Plasma renin levels were measured in one patient; they were markedly elevated pre-operatively, but returned to normal following tumour excision. Immunoreactive renin staining, using a polyclonal antibody to human renin, was performed in the 12 patients. Staining was positive in ten patients. The most intense staining was noted in the areas of cortex entrapped within the tumour, and in perivascular spaces not associated with entrapped cortex. These findings suggest that hypertension secondary to increased tumour associated renin production is a feature of congenital mesoblastic nephroma.

Child, Preschool↗
PubMed1989

Molecular analyses of a five-amino-acid cytotoxic T-lymphocyte (CTL) epitope: an immunodominant region which induces nonreciprocal CTL cross-reactivity.

The cytotoxic T-lymphocyte (CTL) response to lymphocytic choriomeningitis virus infection determines the outcome of infection. Here we show that this response in BALB/c mice (H-2d), when analyzed both at the primary CTL level and using CTL clones, is predominantly monospecific. The vast majority of CTL have a common specificity for a single epitope in the virus nucleoprotein, which can be minimally identified by amino acids GVYMG. This epitope is presented by the Ld class I glycoprotein. We used these data to design a subunit CTL vaccine, whose effectiveness is demonstrated in the accompanying report (L. S. Klavinskis, J. L. Whitton, and M. B. A. Oldstone, J. Virol. 63:4311-4316, 1989). Further analysis indicates that, while CTL clones share a common minimal epitope, they differ in their ability to recognize cells infected with a related but distinct strain of lymphocytic choriomeningitis virus. Studies on the molecular nature of CTL cross-reactivity indicate that CTL induced by similar sequences may cross-react in a unidirectional manner. These novel observations suggest that CTL vaccines, to achieve optimal effectiveness, should not simply include virus sequences which will yield a CTL response; the immunizing sequences should also be selected to ensure that the fine specificities of the induced CTL are such that they maximize the chance of recognizing serotypically diverse strains.

Amino Acid Sequence↗
PubMed1989

Genetic studies of low-abundance human plasma proteins. XII. A new variant of corticosteroid-binding globulin detected by isoelectric focusing/immunoblotting.

Thin-layer polyacrylamide gel isoelectric focusing over the pH range 3.5-5 followed by immunoblotting was used to investigate the occurrence and frequency of genetic variation in corticosteroid-binding globulin (CBG). Plasma samples from US Caucasians (n = 105) and US Blacks (n = 106) from Pittsburgh, Pa., Canadian Indians from Vancouver Island (n = 91) and Nigerian Blacks (n = 116) were analyzed. A complex isoprotein pattern was observed in all individuals tested. Reduction of this pattern to a single primary band following neuraminidase treatment indicates that the observed intraindividual variation is due to variation in the number of sialic acid residues associated with CBG. The CBG variant pattern consisted of a series of isoprotein bands having the same mobility as the common pattern, and a second series of bands at a more acidic isoelectric point. This pattern is consistent with heterozygosity for a rare CBG allele.

Blood Proteins↗
PubMed1989

Renin messenger RNA localization in congenital mesoblastic nephroma using in situ hybridization.

Renin messenger (m) RNA distribution was studied in congenital mesoblastic nephroma, a usually benign renal tumour of early infancy which may be associated with excess renin production and hypertension. Using in situ hybridization with synthetic radiolabelled oligonucleotide probes combined with immunohistochemical studies, renin expression was found in areas of tumours containing recognizable cortical structures including glomeruli and tubules. Renin mRNA was also detected in vessels and larger vascular spaces within the tumour not associated with cortical structures. Cells in the tumour vessel walls and sinusoids which expressed renin also stained positively for vascular smooth muscle-specific alpha actin.

Female↗
PubMed1988

Gummatous penile ulceration and generalised lymphadenopathy in homosexual man: case report.

A case of granulomatous penile ulceration associated with generalised lymphadenopathy in a homosexual man aged 43 is presented. His serum gave positive results to tests for syphilis, but was negative for antibody to human immunodeficiency virus (HIV). His condition responded briskly to treatment with procaine penicillin, and we conclude that the clinical features were attributable to infection with Treponema pallidum.

Adult↗
PubMed1987

Review of an extensive worldwide study of a new H2-receptor antagonist, famotidine, as compared to ranitidine in the treatment of acute duodenal ulcer.

The efficacy and safety of famotidine, a new potent H2-receptor antagonist, has been studied in 1,031 patients by 68 investigators in 19 countries in a worldwide dose-ranging multicenter comparative study. Three doses of famotidine (40 mg h.s., 20 mg b.i.d., 40 mg b.i.d.) were compared to ranitidine 150 mg b.i.d. There were no significant differences between the groups in baseline characteristics, including duodenal ulcer size. Efficacy parameters included daytime and nocturnal symptom relief and duodenal ulcer healing, documented by endoscopy, and defined as complete re-epithelialization of the ulcer crater. Significant reductions from baseline for day and night pain, beginning during the first 24 h period, were found in all four treatment groups (p less than 0.01). There was little difference among the four treatment groups with respect to the percentage of patients healed after 4 and 8 weeks of treatment. Healing rates for the three famotidine groups (40 mg h.s., 20 mg b.i.d., 40 mg b.i.d.) were 88, 92 and 92%, respectively, after 8 weeks of treatment as compared to 91% for the ranitidine group. The occurrence and type of adverse clinical experiences reported was similar for each of the four treatment groups. The most common adverse experiences were headache and diarrhea. The results of this study demonstrate that an h.s. dose of famotidine is equivalent to both b.i.d. famotidine and b.i.d. ranitidine in duodenal ulcer healing and pain relief. In view of possible increased patient compliance with a simplified dosage regimen, famotidine 40 mg h.s. is recommended in the acute treatment of duodenal ulcer.

Acute Disease↗
PubMed1987

Failure of angiotensin converting enzyme inhibition to affect the course of chronic puromycin aminonucleoside nephropathy.

The effects of the angiotensin converting enzyme (ACE) inhibitor enalapril on the proteinuria and degree of focal glomerular sclerosis hyalinosis (FSH) in chronic puromycin aminonucleoside nephropathy (PAN) were examined. Chronic PAN was induced in male Sprague-Dawley rats by seven subcutaneous injections of puromycin aminonucleoside (20 mg/kg) over 10 weeks (Groups I and II). Group II rats also received enalapril 10 mg/kg/day in the drinking water throughout the study (12 weeks). Group III rats served as age-matched controls. Proteinuria was similar in Groups I and II (35.5 +/- 9.7 versus 29.1 +/- 4.1 mg protein/mg creatinine, mean +/- SEM, P greater than 0.05). Serum creatinine remained unchanged in Group I, but rose from 0.7 +/- 0.04 to 1.2 +/- 0.1 mg/dl (mean +/- SEM, P less than 0.05) in Group II. FSH was 13.8% in Group I, 12.9% in Group II (P greater than 0.05), and 0.6% in Group III. There was no significant difference in glomerular lipid content and in immunofluorescence for rat albumin, fibrinogen, IgM, IgG, and C3 between Groups I and II. ACE activity was inhibited by 94% in serum, 83% in lungs, and 92% in kidneys; and blood pressure response to. Angiotensin I challenge was decreased by 50% in rats similarly treated with enalapril versus controls. In summary, proteinuria and glomerular sclerosis in this model are not affected by ACE inhibition.

Angiotensin I↗
PubMed1987

Intramuscular imipenem/cilastatin in the treatment of mild and moderate infections.

Imipenem/cilastatin is the combination of a broad spectrum beta-lactam antibiotic with dehydropeptidase I--an inhibitor of the metabolism of imipenem. Clinical trials have shown that imipenem/cilastatin given intravenously is effective in the treatment of mild, moderate or severe infections. A new milled form of imipenem has been developed for intramuscular use as a suspension with cilastatin, which provides a longer effective half-life of three to four hours with lower peak concentrations of imipenem. A multicenter clinical trial was instituted in the treatment of mild and moderate infections with 500 mg b.i.d. and 500 mg t.i.d. or 750 mg b.i.d., respectively. All 500 mg doses were suspended in saline while the 750 mg doses were in 1% lidocaine. A total of 346 (126 on 500 mg b.i.d., 70 on 500 mg t.i.d. and 128 on 750 mg b.i.d.) were entered. Another 22 patients received a combination of the two regimens. Of the total 346 patients entered, 286 were considered evaluable for efficacy. Skin and soft tissue infections were the most common followed by intra-abdominal, respiratory and urinary tract infections. Overall favorable outcomes were demonstrated in 98.7% with a range of 92 to 100%. All patients were included in the safety analysis. Clinical adverse experiences (AEs) were reported in 3.2% of patients with two AEs considered drug related. Both were pain at the injection site with 500 mg doses. No injection site pain was reported as AEs with the 750 mg doses. Laboratory AEs were reported in 17% and considered drug related in 7% (primarily liver enzymes changes).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1986

Canine chronic renal disease: prevalence and types of glomerulonephritis in the dog.

In a prospective survey, one hundred and eleven dogs with canine chronic renal disease, presenting to 24 veterinary practices in East Anglia and the West Midlands (geographical area 8,600 square miles) were identified. More than 20 different breeds were represented. In 76 cases, clinical details, blood and urine biochemistry, serology and kidney tissue for light and electron microscopy, and immunohistochemistry were obtained. Forty (52%) had glomerular (GN) and 36 (48%) non-glomerular (NGN) disease. Types of GN identified were (W.H.O. classification, number of cases in brackets): focal glomerulonephritis (gn) (5), diffuse mesangial proliferative gn (8), diffuse endocapillary proliferative gn (2), mesangiocapillary gn type I (8), diffuse crescentic gn (1), diffuse sclerosing gn (7), amyloid (6), unclassifiable gn (3). Eight dogs with GN and 13 with NGN had extra-renal lesions. In only one GN case (bacterial endocarditis) was the etiology clear. Proteinuria, but not age, breed, sex, serum creatinine or hematuria, discriminated between GN and NGN groups. This prospective survey identifies GN, with morphological types as found in humans, as a common cause of canine chronic renal disease.

Amyloidosis↗
PubMed1986

Imipenem/cilastatin: a multicentre international study of its clinical efficacy, safety and potential as empirical therapy.

Five hundred and sixty-nine patients were treated with imipenem/cilastatin in this multicentre, international noncomparative study of hospitalized patients with moderate to severe infections; 97.5% of 815 pathogens isolated were susceptible to imipenem, which reconfirms imipenem's broad in-vitro spectrum. Clinical efficacy could be assessed in 389 patients, the majority (72%) of whom received a daily dose of 1.5 g or less. Infections in the various body sites with the exception of the central nervous system were treated. A favourable clinical outcome was seen in 93% of the infections. Fifty-five of the 389 patients had been unsuccessfully treated with one or more antibiotics before being switched to imipenem/cilastatin. In these patients the daily dose was evenly distributed between 1.5 g/day (47%) or 2.0 g/day (40%); the rest of the patients received greater than 2 g/day. Intra-abdominal and respiratory tract infections were the most common, the majority (56%) of which were rated severe. Overall clinical efficacy (cured or improved) in these 55 patients was 82%. With the demonstrated clinical efficacy, particularly in the treatment of proven infections which have failed on other regimens, imipenem/cilastatin could have a distinct advantage as an initial choice for empirical therapy.

Adult↗
PubMed1986

Norfloxacin versus co-trimoxazole in the treatment of recurring urinary tract infections in men.

Norfloxacin is a lipid-soluble weak organic acid bound to plasma proteins to a low extent. Norfloxacin has a pKa1 from 6.2 to 6.4 and a pKa2 from 8.7 to 8.9. Mean concentrations of norfloxacin in prostatic tissue have been reported as 1.7 mg/kg. Recurrent urinary tract infection (UTI) in men is frequently associated with prostatic infection, and chronic prostatitis is both difficult to diagnose and to treat. One hundred and twenty-nine patients were entered into a randomized, open controlled, comparative multiclinic study of the efficacy and safety of norfloxacin vs. co-trimoxazole in male patients with recurrent UTI. Norfloxacin 400 mg and co-trimoxazole 160/800 mg were given twice daily for 4 to 6 weeks. One hundred and nine patients were considered evaluable for efficacy. Norfloxacin effected bacteriologic eradication in 56 of 60 (93%) patients; co-trimoxazole effected eradication in 39 of 49 (67%) patients. This difference in bacteriologic outcome had statistical significance (p less than 0.05). A subset of these patients had prostatic fluid cultures pre- and post-therapy. The eradication rate was 23 of 25 (92%) for norfloxacin and 10 of 15 (67%) for co-trimoxazole. Bacteria isolated were (norfloxacin/co-trimoxazole): E. coli 27/25; K-E-S 14/13; Proteus spp. 7/5; Ps. aeruginosa 2/0; other gram-negative bacilli 4/3; gram-positive cocci 7/3. Four patients, one on norfloxacin and three on co-trimoxazole had drug-related clinical and/or laboratory adverse experiences. None was serious. Norfloxacin appears to be an effective drug for the treatment of recurrent UTI in men.

Anti-Infective Agents, Urinary↗
PubMed1985

Genes encoding the T-cell antigen receptor.

The search for the elusive and controversial T-cell antigen receptor is over. It is now clear that gene complexes for both alpha and beta chains are distinct from those for immunoglobulin genes. They are, however, related to Ig genes as well as to other class I and class II major histocompatibility complex (MHC) gene products. Therefore, they belong to the immunoglobulin super gene family.

DNA, Circular↗