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Biomedical subjects

M Thomas

Publications and source records attributed to M Thomas.

At least 19 recordsLinked to original sources

Structure and expression of a gene from Arabidopsis thaliana encoding a protein related to SNF1 protein kinase.

The AKin10 gene from Arabidopsis thaliana encoding a putative Ser/Thr protein kinase (PK) has been isolated and characterized. The AKin10-encoding gene is located on a genomic 5.4-kb BamHI fragment and contains ten introns, one being located in the 5' untranslated region. The deduced amino acid sequence of AKin10 is 65% identical over the catalytic domain to the yeast PK (SNF1). SNF1 is essential for the derepression of many glucose-repressible genes, including Suc2 which encodes invertase. Southern blot hybridization experiments suggested the presence of one copy of the gene per haploid genome of A. thaliana. Northern hybridization experiments indicated that this gene is expressed in roots, shoots and leaves. AKin10 may play an important role in a signal transduction cascade regulating gene expression and carbohydrate metabolism in higher plants.

Amino Acid Sequence

Use of zinc acetate to treat copper toxicosis in dogs.

Zinc acetate was used for the treatment and prophylaxis of hepatic copper toxicosis in 3 Bedlington Terriers and 3 West Highland White Terriers. Two dogs of each breed were treated for 2 years, and 1 of each breed for 1 year. A dosage of 200 mg of elemental zinc per day was required to achieve therapeutic objectives related to copper, which included a doubling of plasma zinc concentration to 200 micrograms/dl and a suppression of oral 64 copper absorption. The dosage was later reduced to 50 to 100 mg/day to avoid an excessive increase in plasma zinc concentration. The preliminary clinical results were good. Three dogs had mild to moderate active liver disease and high liver copper concentrations at the time of initiation of zinc administration. Biopsy of the liver 2 years later revealed a reduction in hepatitis and copper concentrations. One other dog without active hepatitis also had a reduction in hepatic copper concentrations over a 2-year period. All 6 dogs have done well clinically. On the basis of these findings, we believe zinc acetate to be an effective and nontoxic treatment for copper toxicosis in dogs.

Absorption

C-erbB-2 oncoprotein expression versus internal mammary lymph node metastases as additional prognostic factors in patients with axillary lymph node-positive breast cancer.

The relationship was assessed between c-erbB-2 oncoprotein expression and other prognostic factors in breast cancer, such as axillary and internal mammary node metastases. The value of these indicators was analyzed in estimating prognosis, especially in patients with axillary node-positive breast cancer. These results showed that c-erbB-2 is significantly related to clinical stage and axillary node metastases. A univariate study revealed that disease-free and overall survival were correlated significantly with clinical stage, tumor size, axillary and internal mammary node metastases, and 21N status. Among the patients with axillary node involvement, however, 21N status did not appear to be a significant additional prognostic factor. Internal mammary node metastases were significant. In a multivariate study, only axillary and internal mammary node metastases were significant prognostic factors for either the entire group of patients or those with positive axillary nodes. Therefore, axillary node dissection and biopsy of the internal mammary nodes may provide important prognostic information for patients with breast cancer.

Adult

[Embolizing aortic valve endocarditis in the differential diagnosis of thrombotic thrombocytopenic purpura].

A 50-year-old man complained of lumbar pains, lack of energy, dysarthria and ataxic gait. Investigation revealed progressive anaemia (haemoglobin initially 10.5 g/dl, later 6.8 g/dl) and thrombocytopenia (initially 67,000/microliters, later 25,000/microliters). In addition he had unexplained pyrexia of up to 39.8 degrees C. Lactate dehydrogenase was 780 U/l and fragmented red cells were noted in the blood film. Because of suspicion of thrombotic thrombocytopenic purpura, treatment with fresh plasma by infusion was immediately initiated. On the third day of treatment he developed left ventricular failure; auscultation revealed a blowing early diastolic murmur over Erb's point together with a spindle-shaped early diastolic murmur over the right second intercostal space. Computed tomography of the skull showed recent haemorrhage into the left half of the cerebellum and an older right posterior infarct. The abdominal ultrasound scan suggested a haemorrhagic spleen infarct. In view of these findings the diagnosis was revised to embolizing aortic endocarditis with aortic reflux (confirmed by colour Doppler echo-cardiography). Aortic valve replacement was performed immediately, and the patient was treated with gentamycin 80 mg/d and teicoplanin 400 mg/d for four weeks. Postoperatively he was given 12 units of platelet concentrate and the platelet count remained stable thereafter (greater than 100,000/microliters). Splenectomy became necessary because the splenic haematoma increased in size during oral anticoagulant therapy. After a 6 week hospital stay the patient was discharged in good condition.

Anti-Bacterial Agents

Variation in the P2-S2 stereochemical selectivity towards the enantiomeric N-acetylphenylalanylglycine 4-nitroanilides among the cysteine proteinases papain, ficin and actinidin.

1. Values of the kinetic specificity constant, kcat./Km, for the hydrolysis of N-acetyl-L-phenylalanylglycine 4-nitroanilide (I) and of its D-enantiomer (II) catalysed by ficin (EC 3.4.22.3) and by actinidin (EC 3.4.22.14) at pH 6.0, I 0.1 mol/l, 8.3% (v/v) NN-dimethylformamide and 25 degrees C were determined by using initial-rate data with [S] much less than Km and weighted nonlinear regression analysis as: for ficin, (kcat./Km)L = 271 +/- 6 M-1.s-1, (kcat./Km)D = 2.9 +/- 0.1 M-1.s-1, and for actinidin (kcat./Km)L = 13.3 +/- 0.7 M-1.s-1, (kcat/Km)D = 0.34 +/- 0.01 M-1.s-1.2. These data and analogous values for the corresponding reactions catalysed by papain (EC 3.4.22.2), (kcat./Km)L = 2064 +/- 31 M-1.s-1, (kcat./Km)D = 5.5 +/- 0.1 M-1.s-1, demonstrate marked variation in stereochemical selectivity for substrates (I) and (II) among the three cysteine proteinases with the following values for the index of stereochemical selectivity Iss = (kcat./Km)L/(kcat./Km)D: for papain, 375; for ficin 93; for actinidin 39. 3. Model building suggests ways in which, for the papain-catalysed reactions, binding interactions involving the extended acyl groups of the substrates may need to change as the reaction proceeds from adsorptive complex (ES) to tetrahedral intermediate (THI) before its rate-determining, general acid-catalysed collapse to acylenzyme intermediate. In particular, satisfactory alignment in the catalytic site at the THI stage of the acylation process appears to demand rotation of the substrate moiety about its long axis. 4. The different consequences of this rotation for the L- and D-enantiomers suggest that for closely related systems the greater the extent of this rotational adjustment the greater would be the value of Iss.5. For the actinidin-substrate combinations, model building suggests that even at the ES complex stage of catalysis it is not possible to approach optimized P2-S2 contacts and the three hydrogen-bonding interactions deduced for papain-ligand complexes in the absence of significant movement of protein conformation. Possible binding modes in which some of the interactions deduced for papain are relaxed are discussed. Consideration of postulated binding modes in the various transition states is shown to account for the order of reactivity reflected in values kcat./Km for the four reactions involving papain (Pap) and actinidin (Act) with the L- and D-enantiomeric substrates: Pap-L much greater than Act-L greater than Pap-D much greater than Act-D.(ABSTRACT TRUNCATED AT 400 WORDS)

Anilides

Papillary thyroid cancer and its surgical management.

The surgical management in papillary thyroid cancer has been highly controversial. In the Department of Surgery (II), Kanazawa University Hospital, the surgical management especially for cervical lymph node metastases has changed since 1973 from a conservative approach to an aggressive one. In order to determine whether an aggressive approach is warranted, a retrospective multivariate analysis was carried out on 106 cases of papillary thyroid cancer. The patients have been followed for 10-28 years. Multivariate analysis was conducted following Cox's model. By this analysis, aggressive management appeared to have no impact on survival or relapse-free survival. However, age, sex, tumor size, and cervical lymphadenopathy were confirmed to be important prognostic factors in survival and/or relapse-free survival.

Adult

Oncological aspect of immediate breast reconstruction in mastectomy patients.

In this study, we compared the relapse-free and overall survival of 83 patients who underwent mastectomy with immediate reconstruction (MIBR) using a musculocutaneous flap with or without silicone implant with those of 153 patients with breast cancer who underwent mastectomy without immediate reconstruction. In univariate analysis, the overall and/or relapse-free survival of reconstructed patients with four or more positive axillary lymph nodes or those with menopausal status were significantly inferior compared with those of nonreconstructed patients. In multivariate analysis, however, the immediate breast reconstruction did not appear to have a significant adverse influence on all patients, and on the subgroups stratified by menopausal status or axillary lymph node metastases. Therefore, it was concluded that MIBR using a musculocutaneous flap did not compromise the survival of patients with breast cancer.

Adult

The influence of obesity on left ventricular filling and systolic function.

Little information on the possible influence of obesity on diastolic function is available. Thus we studied 24 asymptomatic obese volunteers (greater than 120% ideal body weight; mean 153 +/- 30%), aged 34 +/- 11 years. Each obese subject was matched for age, height, and sex, with a healthy normal-weight control subject. Isovolumic relaxation time (IVRT) and diastolic filling indexes were determined by pulsed Doppler echocardiography. The IVRT was significantly prolonged in the obese group (84 +/- 17 msec) as compared with the control group (57 +/- 13 msec; p less than 0.0002). Multiple regression analysis showed that percentage of ideal body weight was the most important predictor of peak early filling velocity (r = 0.59, p less than 0.005) and mean deceleration rate of early filling (r = 0.61, p less than 0.005) in the obese group. However, age as compared with percentage of ideal body weight was a more important determinant of the relative distribution of early and atrial filling, such as peak early-to-atrial filling velocity ratio (r = -0.75, p less than 0.0001). Ejection fraction, heart rate, and blood pressure did not differ between the obese and control groups. In conclusion, obesity is associated with preclinical abnormalities of IVRT, which may reflect impaired relaxation. The IVRT may be useful in the early detection of left ventricular dysfunction in obesity. Last, studies comparing Doppler indexes of diastolic filling among groups must control for potential differences in percentage of ideal body weight.

Adolescent

Gender influences the in vitro renin release responses to dopamine and adrenergic receptor blockade in the summer-active ground squirrel Spermophilus lateralis.

1. 10(-4) M Dopamine stimulated and 10(-7) M inhibited in vitro resting renin release (RR) only in the female animals. 2. Alpha- or beta-adrenergic blockade prevented the stimulation but not the inhibition of RR by dopamine in the female animals. 3. Membrane receptor mechanisms mediating these changes do not involve alterations in tissue cyclic AMP content. 4. The sensitivity of the juxtaglomerular cells to dopamine challenge is gender dependent during summer activity.

Adrenergic Antagonists

Wide resection with latissimus dorsi muscle transposition in breast conserving surgery.

In this study we evaluated whether the immediate transposition of the latissimus dorsi muscle (LDM) improves breast appearance and patient satisfaction after quadrantectomy. Twenty-three patients (transposed group) had the transposition of LDM immediately after quadrantectomy, but eight patients (non-transposed group) had quadrantectomy alone. For evaluation, breast size was classified as small (A or B cup) and large (C or D cup). Consequently, the cosmetic result was evaluated as excellent in 73% of the patients with transposed small breasts, but in only 25% of the patients with non-transposed small breasts and by none of the patients with transposed large breasts. On the other hand, all patients with transposed small breasts reported that they are satisfied with their operation, as opposed to 88% of the patients with transposed large breasts and 63% of the patients with transposed large breasts and 63% of the patients with non-transposed small breasts. It was concluded therefore, that the transposition of LDM is useful in correcting post-quadrantectomy breast deformity, especially in patients with small breasts.

Adult

[The pulmonary first pass effect of noradrenaline following intravenous and endobronchial administration for resuscitation].

In a porcine CPR-model, we investigated the pharmacokinetics and pharmacodynamics of norepinephrine (NE) after intravenous (10 g/kg, n = 10, group A) and endobronchial (e.b., 100 micrograms/kg, n = 10, group B) administration. After 3 min of cardiac arrest induced by electroshock, restitution of spontaneous circulation (ROSC) was achieved in 8 animals in group A after 3.3 +/- 1.6 min, and in group B in 6 animals after 2.5 +/- 0.6 min. Haemodynamics during CPR were not significantly different, but during the first hour after ROSC e.b. NE showed a depot effect. Maximum venous (642 +/- 182 ng/ml after 3.5 +/- 0.3 min) and arterial (147 +/- 21 ng/ml after 4.2 +/- 0.4 min) NE concentrations in group A were significantly higher compared with values in group B (77 +/- 18 ng/ml after 5.5 +/- 0.5 min venous, 46 +/- 11 ng/ml after 6.0 +/- 0.7 min arterial). The area under the curve (AUC) in group A was calculated to be 55 +/- 12 ng/ml min (venous) and 35 +/- 7 ng/ml min (arterial) representing a pulmonary first-pass effect of 40%. In group B, the dose-adjusted AUC (39 +/- 13 ng/ml min venous, 30 +/- 10 ng/ml min arterial) represented a pulmonary first-pass effect of only 25%. Despite this lower pulmonary first pass, however, it is concluded that after e.b. administration of NE absorption is too much delayed and peak concentrations are too low. Therefore, NE should not be given via this route during CPR.

Animals

The novel 21-aminosteroid U74006F attenuates cerebral edema and improves survival after brain injury in the rat.

The present study evaluated the effect of the nonglucocorticoid 21-aminosteroid U74006F, an inhibitor of iron-dependent lipid peroxidation, on the development of regional cerebral edema after lateral fluid-percussion (FP) brain injury. Male Sprague-Dawley rats (n = 40) were anesthetized and subjected to FP brain injury of moderate severity centered over the left parietal cortex (2.5-2.6 atms). Fifteen minutes after brain injury, animals randomly received an i.v. bolus of either U74006F (3 mg/kg, n = 21) followed by a second bolus (3 mg/kg) at 3 hr or buffered sodium citrate vehicle (equal volume, n = 15). An additional group of 12 surgically prepared but uninjured animals served as preinjury controls. At 48 hr after injury, animals were sacrificed and brain tissue assayed for water content and regional cation concentrations. With the use of specific gravimetric techniques, no significant differences were observed in posttraumatic cerebral edema between drug- and control-treated animals. However, using wet weight/dry weight methodology, we found that administration of U74006F significantly reduced water content in the right hippocampus (contralateral to the site of injury) compared to saline-treated animals (p less than 0.05). U74006F also significantly prevented the postinjury increase in sodium concentrations in the ipsilateral hippocampus (p less than 0.05) and thalamus (p less than 0.03). Regional concentrations of potassium were unaltered after drug treatment. Administration of U74006F significantly reduced postinjury mortality, from 28% in control animals to zero in treated animals (p = 0.01). These results suggest that lipid peroxidation may be involved in the pathophysiological sequelae of brain injury and that 21-aminosteroids may be beneficial in the treatment of brain injury.

Animals

Purification and characterisation of elastase from Staphylococcus epidermidis.

An elastase of Staphylococcus epidermidis was purified by ion exchange chromatography on CM-Sepharose and characterised. Its M(r) is c. 21 kDa, its optimal temperature for activity is 42 degrees C and the pH optimum is 6.8. The enzyme is activated by cysteine and other SH-donators and inhibited by L-trans-epoxy-succinylleucylamido-(4-guanidino)butane (E64), an inhibitor of cysteine proteases, but not by 3,4-dichloroisocoumarin (3,4-DCI), an inhibitor of serine proteases. This finding suggests that the elastase of S. epidermidis is a cysteine protease. Because S. epidermidis elastase degrades human sIgA, IgM, serum albumin, fibrinogen, and fibronectin, this enzyme may be regarded as a virulence factor.

Chromatography, Ion Exchange

Is acupuncture an alternative in idiopathic pain disorder?

This study investigated the pain-relieving effect of an intensive type of periosteal acupuncture stimulation in patients with idiopathic pain disorder. Twelve patients, 2 males and 10 females, with a mean age of 54, were included in the study. The average duration of their pain was 12.6 years. Each treatment consisted of brief but painful manual stimulation of 3 to 4 periosteal sites. Over a 3-8-month period each patient had between 4-11 treatments, an average of 7. Analgesic drugs that patients were on prior to the study were continued but no other physical or psychological treatment for their pain was applied. Ten patients had either no responses to treatment or only transient responses which were not maintained until the following treatment. Two patients benefitted from treatment, having long periods of substantial pain reduction. All responses were assessed on pain scales maintained daily before and during the entire period of treatments. For the majority (83%) of patients in this study, with an idiopathic pain disorder, periosteal acupuncture stimulation was not a treatment alternative.

Acupuncture Therapy

Development of prolonged focal cerebral edema and regional cation changes following experimental brain injury in the rat.

The present study examined the formation of regional cerebral edema in adult rats subjected to lateral (parasagittal) experimental fluid-percussion brain injury. Animals receiving fluid-percussion brain injury of moderate severity over the left parietal cortex were assayed for brain water content at 6 h, 24 h, and 2, 3, 5, and 7 days post injury. Regional sodium and potassium concentrations were measured in a separate group of animals at 10 min, 1 h, 6 h, and 24 h following fluid-percussion injury. Injured parietal cortex demonstrated significant edema, beginning at 6 h post injury (p less than 0.05) and persisting up to 5 days post injury. In the hippocampus ipsilateral to the site of cortical injury, significant edema occurred as early as 1 h post injury (p less than 0.05), with resolution of water accumulation beginning at 3 days. Sodium concentrations significantly increased in both injured cortex (1 h post injury, p less than 0.05) and injured hippocampus (10 min post injury, p less than 0.05). Potassium concentrations fell significantly 1 h post injury within the injured cortex (p less than 0.05), whereas significant decreases were not observed until 24 h post injury within the injured hippocampus. Cation alterations persisted throughout the 24-h post injury period. These results demonstrate that regional brain edema and cation deregulation occur in rats subjected to lateral fluid-percussion brain injury and that these changes may persist for a prolonged period after brain injury.

Animals

Measurement of vascular access recirculation without contralateral venous puncture.

The rate of recirculation is an important variable in calculating the correct dose of dialysis delivered to a patient. Traditionally it is calculated using blood results obtained from the arterial and venous lines and from venous puncture of the opposite arm. To avoid this venipuncture, cessation of the blood pump for 1 or 2 min was attempted to mimic the systemic circulation. This technique underestimated recirculation but was statistically correlated with the result obtained by the classical method, thus it is possible to derive a formula to obtain the recirculation value without contralateral venipuncture.

Adult

Effects of switching from a high-fat diet to a low-fat diet on tumor proliferation and cell kinetics of 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats.

We investigated the stimulatory effect of a high-fat diet on tumorigenesis, tumor proliferation and cell kinetics of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in Sprague-Dawley rats, and sought to determine whether switching the animals from a high-fat diet to a low-fat diet would suppress tumor proliferation and cell kinetics. The high-fat diet significantly stimulated tumorigenesis, tumor proliferation and cell kinetics. After the animals were switched from the high-fat diet to the low-fat diet, however, tumor growth decreased, the BrdUrd labeling indices of tumors significantly decreased, and the potential doubling times of tumors significantly increased. Therefore, switching from a high-fat diet to a low-fat diet may improve the prognosis of breast cancer.

9,10-Dimethyl-1,2-benzanthracene