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Biomedical subjects

N Thomas

Publications and source records attributed to N Thomas.

At least 163 records · Page 9Linked to original sources

[Can piperacillin modify the experimental nephrotoxicity of gentamicin?].

A synergistic effect of antibacterial activity has been demonstrated with piperacillin combined with an aminoglycoside. Four groups of 30 female Wistar rats were injected daily for 14 days with either gentamicin 50 mg/kg, or piperacillin 1,000 mg/kg, or both drugs combined; the control group received sodium chloride in solution. In all groups, creatinine clearance, lysosomal structural latency and renal cortex enzyme activities (alanine-aminopeptidase, N-acetyl beta D-glucosaminidase, sphingomyelinase, cathepsin B) were measured on days 2, 4, 7, 10 and 14 of treatment. Renal cortex concentrations of gentamicin were measured in the group that received gentamicin alone and in the group treated with both piperacillin and gentamicin. The renal functional changes usually induced by aminoglycosides were observed. Piperacillin administered alone reduced creatinine clearance and alanine-aminopeptidase activity. The piperacillin-gentamicin combination proved unable to prevent the fall in creatinine clearance; it also reduced the alanine-aminopeptidase, sphingomyelinase and cathepsin B activities, but the reduction was less pronounced than that induced by gentamicin alone.

Animals↗

Treatment of acute myocardial infarction with anisoylated plasminogen streptokinase activator complex.

A controlled trial in 149 patients admitted to a district hospital with probable myocardial infarction tested the effect of 30 units of anisoylated plasminogen streptokinase activator complex (APSAC) on indices of infarct size. Patients were grouped prospectively according to whether they entered the trial within two and a half hours (early entry) or between two and a half and four hours (late entry) after onset of the symptoms. Sixty seven of 73 patients in the control group showed increased plasma activity of myocardial creatine kinase isoenzyme that was diagnostic of infarction compared with only 60 of 76 who received APSAC. The difference was significant overall but occurred predominantly in the early entry group. The patients who received APSAC had more early ventricular arrhythmias, compatible with reperfusion, and showed greater preservation of R waves during admission to hospital. Unwanted effects were generally minor and more common in the actively managed group than the control group (26% v 3%). After nine to 12 months of follow up 12 patients in the control group had died compared with seven in the actively managed group. The ease of administration and the apparent efficacy of APSAC suggest that it is suitable for use in a district hospital for patients with suspected acute myocardial infarction.

Anistreplase↗

The use of flanking markers in prediction for Duchenne muscular dystrophy.

Seventy three sisters of boys with Duchenne muscular dystrophy and their families were studied using up to seven deoxyribonucleic acid (DNA) probes linked to the gene on the short arm of the X chromosome. Fifty three (73%) were informative for flanking markers, a further 18 (24%) being informative for a single marker only. Predictions based on pedigree structure and creatine kinase information from the individuals and their female relatives gave more than half (55%) of the sisters a risk for being a carrier of below 10% or above 90%. The addition of information derived from the inheritance of flanking DNA markers, where they exist, improves the situation so that many more sisters (77%) can be allocated into either high or low risk categories.

Adolescent↗

Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur.

A retrospective multi-institutional study of 227 patients with osteosarcoma of the distal end of the femur was done to compare rates of local recurrence, metastasis, and survival. Three cohorts of patients who had had either a limb-sparing procedure, an above-the-knee amputation, or disarticulation of the hip were compared. The results revealed prevalences of eight of seventy-three, nine of 115, and zero of thirty-nine as to local recurrence; forty-three of seventy-three, sixty-five of 115, and twenty-one of thirty-nine as to metastasis; and thirty-three of seventy-three, forty-eight of 115, and eighteen of thirty-nine as to death. Of the seventeen patients who had a local recurrence, sixteen died. In the limb-salvage group, eighteen patients required amputation, because of local recurrence in eight and other local complications in ten. The Kaplan-Meier estimates of the percentage of patients who survived and the percentage of patients without recurrent disease showed no difference among the three surgical groups (Mantel-Cox test statistic: p = 0.8) after a median length of follow-up of five and one-half years. Various covariant adjusted estimates yielded similar results. For the entire group of patients, the rate of continuously disease-free survival was 42 per cent, and the over-all rate of survival was 55 per cent at five years. It appears that, compared with above-the-knee amputation or disarticulation of the hip, the use of a limb-salvage procedure for osteosarcoma of the distal end of the femur did not shorten the disease-free interval or compromise long-term survival.

Adolescent↗

Desmopressin and bleeding time in patients with cirrhosis.

Desmopressin acetate 0.3 microgram/kg was given intravenously to nine patients with chronic liver disease and to a further six such patients in a double blind controlled study versus placebo. Desmopressin acetate significantly shortened the bleeding time compared with basal values in both groups and compared with placebo. There was also a significant decrease in partial thromboplastin time (but not prothrombin time) and significant increases in factor VIII and its components, von Willebrand factor and ristocetin cofactor activity, but not in factors VII, IX, X, XI, or XII. Increased fibrinolysis could be blocked by concomitant administration of tranexamic acid. No important side effects were seen. The multimer pattern of von Willebrand factor was studied for the first time in chronic liver disease. It was normal, but after administration of desmopressin acetate the percentage of multimers of higher molecular weight increased significantly. This may be an important mechanism in the shortening of the bleeding time in cirrhosis, as has been shown in uraemia and other conditions after administration of desmopressin acetate. Desmopressin acetate may be useful in correcting defects in primary haemostasis in chronic liver disease.

Bleeding Time↗

Exsanguination due to gastric ulceration in a foal.

An Arabian foal with a congenital heart disease died due to hemorrhage secondary to a large gastric ulcer. Previously, death of foals with gastric ulcers has been due to diffuse peritonitis resulting from gastric ulcer perforation. The foal in this case report died due to hemorrhage secondary to a large gastric ulcer.

Animals↗

In vitro differentiation of Trypanosoma cruzi under chemically defined conditions.

Metacyclic trypomastigotes of Trypanosoma cruzi have been obtained in chemically defined axenic culture. The differentiating medium, composed of artificial triatomine urine supplemented with proline, allows high yields of metacyclic trypomastigotes after 72-h incubation of T. cruzi cells at 27 degrees C. Morphological differentiation of the parasites is gradual under these chemically defined conditions and is preceded by the expression of stage-specific polypeptides. The yield of in vitro-induced metacyclic trypomastigotes depends upon the age of the epimastigote culture, the size of the inoculum and the depth of the medium. Metacyclic trypomastigotes differentiated in vitro from the Dm 28c clone of T. cruzi are both resistant to complement lysis and to macrophage digestion. They are able to infect mice with an efficiency similar to that obtained for natural metacyclic trypomastigotes obtained from triatomine excreta.

Amino Acids↗

Reverse transport of the deceased neonate--an aid to mourning.

Parents whose infant has died mourn in a fashion similar to others who experience a significant loss. Seeing and touching the dead infant often facilitate the parents' mourning process. If an infant is transported to another facility for care, and dies while the mother remains hospitalized, the mother may never see her infant again. We have found, in selected cases, that returning the dead infant to its mother at the referring hospital can greatly facilitate parental grieving. Parents who have participated in this aspect of grieving later describe it as a very positive factor in their mourning process.

Attitude to Death↗

An antipeptide antibody that specifically inhibits insulin receptor autophosphorylation and protein kinase activity.

Two site-specific antibodies that immunoprecipitate the human insulin receptor have been prepared by immunizing rabbits with chemically synthesized peptides derived from the cDNA-predicted amino acid sequence of the beta subunit of the proreceptor. Antibodies to the carboxyl terminus (AbP5) and to a domain around tyrosine-960 (AbP4) specifically recognize the beta subunit of the receptor on immunoblots. Both antibodies immunoprecipitated 125I-labeled insulin-receptor complexes and the autophosphorylated receptor. Although neither antibody inhibited insulin binding to the receptor, both insulin-dependent autophosphorylation and exogenous substrate phosphorylation were inhibited by AbP4. Inhibition by AbP4 was dependent upon the phosphorylation state of the receptor; it was not detected when the receptor was autophosphorylated prior to addition of AbP4. AbP4 did not inhibit activity of the related epidermal growth factor (EGF)-receptor tyrosine protein kinase nor did it inhibit the activity of cAMP-dependent kinase or protein kinase C. The observation that an antibody directed to residues 952-967 of the proreceptor neutralizes the protein kinase activity of the beta subunit suggests that this region may play a critical role in the function of the hormone-dependent, protein tyrosine-specific kinase activity of the insulin receptor.

Amino Acid Sequence↗

Preferential solubilization of Triton X-100 resistant nuclear glucocorticoid receptors by deoxyribonuclease I.

Nuclei, prepared by hypo-osmotic lysis from rat thymocytes that had been incubated at 37 degrees C with 20 nM [1,2,4-3H] triamcinolone acetonide, contained 2600-2800 stably and specifically bound steroid molecules per nucleus, 70-80% of which were retained after treatment with Triton X-100. DNAase I was more effective than DNAase II in solubilizing detergent-resistant glucocorticoid-receptor complexes from nuclei at both 0 degrees C and 37 degrees C; at 0 degrees C, DNAase I digestion released 50-55% of the bound steroid with only 10% digestion of DNA. These results imply that the glucocorticoid-receptor complex is preferentially associated with transcriptionally active chromatin.

Animals↗

Studies of the mechanism of glucocorticoid-induced pyknosis in isolated rat thymocytes.

The lethal action of glucocorticoids on rat thymocytes in vitro is associated with the progressive accumulation of cells that display a discrete reduction in size. Techniques for the separation and quantitation of these structurally transformed cells have now been used to investigate the relationship between cell size changes and the effects of dexamethasone treatment on chromatin condensation and DNA fragmentation. The steroid-induced reduction in thymocyte size was invariably and exclusively associated with morphologically evident chromatin condensation and with fragmentation of DNA into units that were acid-precipitable but failed to sediment on low-speed centrifugation. The generation of cells of reduced size in response to dexamethasone was inhibited by actinomycin D, cordycepin and cycloheximide; the kinetics of inhibition indicate that glucocorticoid-induced cell death depends on the synthesis, processing and translation of mRNA coding for a protein or proteins whose subsequent lethal effect is expressed in a stochastic manner.

Animals↗

Growth and histology of four canine mammary tumour lines established in nude mice.

A colony of nude (BALB/c/Nu/Nu) mice has been established and used to produce and study transplantable tumour lines derived from spontaneously occurring canine mammary neoplasms. Four primary tumours of differing morphological types were studied. Two were adenocarcinomas (MS306 and PD6014) with varying degrees of differentiation, the third (F5010) was a complex adenocarcinoma composed of both stromal and epithelial elements and the fourth (V5500) was a fibrosarcoma. Tumour fragments were implanted into the subcutaneous tissue of 4- to 6-week-old mice and resulted in tumour growth in each case. There was a latent period of 1 month for tumours PD6014, F5010 and V5500 and of 3 months for tumour MS306 before tumour growth ensured. After serial transplantation this period decreased to 1-2 weeks for the first 3 tumours and to 6 weeks for the last. After the initial lag period, tumour volume increased logarithmically in all cases with doubling times of 6-20 days. Each tumour line has been passaged through 3 serial transplantations with 3 of the tumours retaining their original histological appearance whilst the fourth became slightly more dedifferentiated.

Adenocarcinoma↗

Initial characterisation of oestrogen receptors in canine mammary tumour lines maintained in nude mice.

Proteins binding oestradiol with high affinity and low capacity have been characterised and quantitated in 4 newly established canine mammary tumour lines, MS306, V5500, F5010 and PD6014, maintained in nude mice. These receptor proteins, specific for oestrogens, were found in all the tumour lines, both in initial implants and all subsequent passages. Receptors had equilibrium dissociation constants for oestradiol in the range of 33-210 pM, and sedimentation coefficients of 4 S and 8 S.

Animals↗

Modification of the catalytic subunit of bovine heart cAMP-dependent protein kinase with affinity labels related to peptide substrates.

The modification and concomitant inactivation of the catalytic subunit of bovine heart cAMP-dependent protein kinase with affinity analogs of peptide substrates potentially capable of undergoing disulfide interchange with enzyme-bound sulfhydryl groups have been used to probe the active site associated with peptide binding. The regeneration of catalytic activity on treatment of the modified enzymes with dithiothreitol and the observation that prior reaction with 5,5'-dithiobis-(2-nitrobenzoic acid) blocks the modification of the kinase by these reagents are consistent with the proposal that only thiol residues are reacting. The affinity analog Leu-Arg-Arg-Ala-Cys(3-nitro-2-pyridinesulfenyl)-Leu-Gly, 1, and the closely related peptide AcLeu-Arg-Arg-Ala-Cys(3-nitro-2-pyridinesulfenyl)-Leu-Gly-OEt, 3, react with a single sulfhydryl as shown by the stoichiometry of the release of the 3-nitro-2-pyridinesulfenyl group and the amount of label incorporated in the enzyme when the radioactively labeled peptide analog of 3 (peptide 4) is employed as the modifying agent. The kinetics of the reaction of 1 with 4.3 microM catalytic subunit was monophasic (employing substrate in excess conditions), yielding an apparent value of KI of approximately 40 microM and a k2 value of approximately 0.25 s-1. The low value of the observed KI, together with the observation that protein kinase substrates inhibit the modification reactions, suggest strongly that the cysteine residue undergoing reaction is in the vicinity of the active site. By trypsin-catalyzed degradation and identification of the peptide segment modified by covalent attachment of the peptide portion of the radioactive analog 4, the single cysteine modified was identified as cysteine-198.

Affinity Labels↗

Studies on a stable, mild diabetes induced by streptozotocin in rats.

A stable, mild diabetes in rats maintained on a normal laboratory diet was induced by a single i.p. injection of streptozotocin. Irreversible damage of the pancreatic islet B cells was complete by 3 days after treatment and plasma immunoreactive insulin was undetectable throughout the remaining 12-week period of investigation. The diabetes was characterized by hyperglycaemia of over 30 mM and a constant elevation of plasma alanine and branch-chain amino acids throughout the 12 weeks. In contrast to severe diabetes, plasma free fatty acids rose only gradually from normal values to reach 1.5 mM by week 12, ketone bodies were only slightly elevated (0.7 mM maximum) and liver glycogen was maintained throughout at around 30% of the normal, fed value. Starvation for up to 40 h caused only slight changes (in contrast with non-diabetic animals) and in particular no changes in free fatty acid or ketone bodies were found. These metabolic results are discussed in relation to the mechanisms thought to control those processes.

Amino Acids↗