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Biomedical subjects

M L Thomas

Publications and source records attributed to M L Thomas.

At least 19 recordsLinked to original sources
PubMed1992

Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences.

Protein tyrosine phosphatases (PTPases) are a family of enzymes important in cellular regulation. Characterization of two cDNAs encoding intracellular PTPases expressed primarily in hematopoietic tissues and cell lines has revealed proteins that are potential regulators of signal transduction. One of these, SHP (Src homology region 2 [SH2]-domain phosphatase), possesses two tandem SH2 domains at the amino terminus of the molecule. SH2 domains have previously been described in proteins implicated in signal transduction, and SHP may be one of a family of nonreceptor PTPases that can act as direct antagonists to the nonreceptor protein tyrosine kinases. The SH2 domains of SHP preferentially bind a 15,000-Mr protein expressed by LSTRA cells. LSTRA cells were shown to express SHP protein by immunoprecipitation, thus demonstrating a potential physiological interaction. The other PTPase, PEP (proline-, glutamic acid-, serine-, and threonine-rich [PEST]-domain phosphatase), is distinguished by virtue of a large carboxy-terminal domain of approximately 500 amino acids that is rich in PEST residues. PEST sequences are found in proteins that are rapidly degraded. Both proteins have been expressed by in vitro transcription and translation and in bacterial expression systems, and both have been demonstrated to have PTPase activity. These two additional members of the PTPase family accentuate the variety of PTPase structures and indicate the potential diversity of function for intracellular tyrosine phosphatases.

Amino Acid Sequence↗
PubMed1992

Regulation of duodenal insulin-like growth factor I and active calcium transport by ovariectomy in female rats.

There is a significant body of data that supports the concept that reproductive hormones in females have effects on duodenal calcium transport that are not mediated via altered circulating concentrations of 1,25-dihydroxyvitamin D (1,25(OH)2D). Previously, we have shown parallel alterations in duodenal Ca transport and longitudinal bone growth rate in sexually maturing female rats in response to ovariectomy and estradiol (E) treatment of ovariectomized (OVX) rats (OVX+E) without any change in circulating levels of 1,25(OH)2D or parathyroid hormone. Results are presented here from experiments designed to: (i) further explore the relationship between 1,25(OH)2D and ovarian status in the regulation of duodenal calcium transport, and (ii) determine whether OVX and E replacement alter circulating and duodenal levels of insulin-like growth factor I (IGF-I) that might be related to effects on Ca transport. Growth hormone, which has been shown to affect intestinal Ca absorption and vitamin D metabolism, is thought to act indirectly by stimulating IGF-I. Six-week-old female rats were OVX, given estradiol implants (OVX+E), and fed a diet containing either 0.5% or 0.1% Ca for 3 weeks. In both diet groups, the OVX animals exhibited a higher level of Ca transport, as measured by the everted gut sac method, than either the intact controls or the OVX+E group; there was no difference in calcium transport between the different diet groups. Although there was no difference in circulating levels of 1,25(OH)2D among the intact, OVX, and OVX+E groups fed either diet, animals fed the 0.1% Ca diet had higher circulating levels of 1,25(OH)2D than those fed the 0.5% Ca diet. There was no difference in duodenal levels of calbindin9K among intact, OVX, and OVX+E animals in either diet group, although the animals fed the 0.1% Ca diet had higher levels of calbindin9K than the animals fed the 0.5% Ca diet. In animals fed the 0.5% Ca diet, OVX resulted in elevated serum and duodenal levels of IGF-1, as compared with intact and OVX+E animals on the same diet. In animals fed the 0.1% Ca diet, there was no elevation of IGF-I in the OVX group relative to intact and OVX+E animals. These results lend additional support to the concept that alterations in duodenal active calcium transport that occur with alterations in ovarian hormones are not mediated by changes in serum levels of 1,25(OH)2D, but may be related to some factor related to growth, possibly IGF-I.

Animals↗
PubMed1992

Testosterone alters duodenal calcium transport and longitudinal bone growth rate in parallel in the male rat.

Duodenal active calcium transport and longitudinal bone growth rate have been shown previously to be regulated in parallel by alteration of gonadal hormone status in sexually maturing female rats. The present study was designed to extend these observations to the sexually maturing male rat. Male rats were orchidectomized (ORX) and given Silastic implants containing either testosterone or estradiol at 6 weeks of age. At 9 weeks of age, duodenal active calcium transport was measured by the everted gut sac method and longitudinal bone growth rate was determined by tetracycline labeling. Decreases in body weight, longitudinal bone growth rate, duodenal calcium transport, and serum Ca and P were exhibited by ORX animals as compared with age-matched control animals. Testosterone administration to ORX animals resulted in an increase in body weight, longitudinal bone growth rate, duodenal calcium transport, and serum Ca and P as compared with ORX animals to a level not significantly different from that of age-matched control animals. Estradiol administration to ORX animals resulted in an additional decrease in body weight, although no significant effect on duodenal calcium transport, serum Ca, or P was noted as compared with ORX animals. There were no statistically significant alterations in the circulating levels of 1,25-dihydroxyvitamin D, parathyroid hormone, or osteocalcin in response to any of the experimental manipulations of gonadal status. These results indicate that, as in the female, gonadal hormone status affects intestinal calcium transport in sexually maturing male rats in parallel with changes in bone growth rate by mechanisms that are independent of circulating levels of 1,25-dihydroxyvitamin D.

Animals↗
PubMed1992

The development and testing of a nursing model of morbidity in patients with cancer.

Although oncology nurses are concerned about patient morbidity associated with cancer and its treatment, a comprehensive morbidity model from the perspective of nursing has yet to be developed. The purpose of this study was to begin to develop a morbidity model relevant to patients with cancer receiving treatment in the ambulatory care setting. The model was empirically tested with a sample of 100 patients with cancer beginning chemotherapy. Three domains emerged from the model: physiologic/pathophysiologic, functional, and psychological. Indices of morbidity within each domain were tested to establish beginning reliability and validity of the model. The results that were obtained indicate significant correlations among many of the indices within each domain (e.g., performance status, mood disturbance, patients' ratings of their current health); other indices did not contribute significantly to the model (e.g., type of cancer, history of recurrent disease, and patients' assessments of their health prior to developing cancer). Although further testing and refinement of the model is indicated, these preliminary findings reflect the model's potential for significant clinical relevance. By using this model, nurses could more readily profile patients at risk for increased morbidity and target their interventions accordingly.

Activities of Daily Living↗
PubMed1979

The value of large volume selective arteriophlebography of the renal veins in the pre-operative assessment of renal carcinoma.

The accuracy of large volume selective arteriophlebography in demonstrating the main renal veins in 28 patients with renal carcinoma is presented. The diagnosis was shown to be correct at operation in 96% of examinations. It is suggested that the technique is valuable and safe and should form part of the routine pre-operative assessment of patients with renal carcinoma.

Adult↗
PubMed1979

Pharmacokinetic properties of netilmicin in newborn infants.

Netilmicin and gentamicin susceptibilities of 258 gram-negative organisms and 25 strains of Staphylococcus aureus were nearly identical. The pharmacokinetic properties of netilmicin were evaluated in 101 newborn infants and related to birth weight, gestational age, chronological age, and route of administration. Mean peak serum concentrations of 5.6 to 6.9 and 7.8 to 8.4 mug/ml were observed 30 min after 3- and 4-mg/kg doses, respectively, were given intramuscularly. The peak concentrations were directly related to gestational age. The average serum half-life values varied from 3.4 to 4.7 h and in general were inversely related to birth weight, gestational age, and postnatal age. The pharmacokinetics of netilmicin in 10 infants were similar after intramuscular and intravenous administration. A comparative study of netilmicin and gentamicin in seven neonates revealed greater variability in serum concentrations of gentamicin and a shorter half-life for netilmicin. There was evidence of accumulation of netilmicin in 12 low-birth weight, premature infants who received 4-mg/kg doses for an average of 6.4 days. Serum and urine levels of netilmicin were measured up to 11 days after discontinuation of the drug. These data are well characterized by a two-compartment model. Additional studies of efficacy and long-term toxicity of netilmicin in neonates are necessary.

Bacteria↗
PubMed1979

Comparative pharmacokinetics of amoxicillin and ampicillin in infants and children.

The pharmacokinetics of amoxicillin and ampicillin were studied in 24 infants and children. Mean peak serum concentrations of 5.4 micrograms/ml in fasting and 3.2 micrograms/ml in nonfasting patients were observed after 15 mg/kg amoxicillin doses. Area under the curve values and serum half-life values were similar in fasting and nonfasting patients. The pharmacokinetics of amoxicillin (15 mg/kg) were compared to those of ampicillin (25 mg/kg). Peak serum concentrations, area under the curve values and half-life times were comparable for the two drugs. Amoxicillin (25 mg/kg) and ampicillin (25 mg/kg) were compared in cross-over fashion in 11 children. Serum concentrations of amoxicillin were consistently larger than those of ampicillin; the differences were of borderline significance at one and two hours and statistically significant at four and six hours after the dosage. The bioavailability of amoxicillin was twice that of ampicillin. Amoxicillin was detected in approximately half of the saliva samples studied. Although the salivary concentrations in many children exceeded the inhibitory level for most pneumococci and group A streptococci and for many non-beta lactamase-producing Haemophilus influenzae type b strains, the clinical relevance of these observations is unknown.

Amoxicillin↗
PubMed1978

Complications of ascending phlebography of the leg.

Forty patients were studied prospectively for complications of ascending phlebography. The commonest immediate complication was pain at the site of injection and the commonest delayed complication pain in the foot or calf. Out of 30 patients with pain in the foot and calf, 15 had venous thrombosis. Review of 200 case notes disclosed only one recorded complication--namely, necrosis of the dorsal skin of the foot. Complications of the procedure reported by referring clinicians over 10 years comprised four cases of necrosis of the dorsum of the foot and two of gangrene of the foot, in one of which the gangrene spread to the leg. Major complications of ascending phlebography are rare, though when they occur may cause serious morbidity. If a scrupulous technique is used contrast phlebography remains the most accurate method of diagnosing venous disease of the leg.

Foot Dermatoses↗
PubMed1978

Clinical pharmacology of cefadroxil in infants and children.

The pharmacokinetics of cefadroxil suspension were studied in 30 children, 13 months to 12 years of age (mean age, 5.7 years). Average peak concentrations in serum of 11 to 14 mug/ml and of 7 to 10 mug/ml after 15- and 10-mg/kg doses, respectively, were not substantially affected by the feeding status. The serum half-life values were 1.3 to 1.5 h. Cefadroxil was detected in saliva of all children 2 h after 15-mg/kg doses: the levels ranged from 0.17 to 2.6 mug/ml (mean, 0.46 mug/ml). The average concentrations in urine were 1,700 and 2,620 mug/ml at 0 to 2 and 2 to 4 h, respectively, after 15-mg/kg doses. In a randomized controlled study of 50 children with impetigo, cefadroxil was as effective as penicillin G in curing existing lesions and in preventing development of new lesions. Cefadroxil may be useful for therapy of mucocutaneous and urinary tract infections in infants and children.

Biological Availability↗
PubMed1978

Coronary artery ectasia--a variant of occlusive coronary arteriosclerosis.

In a study of 1000 consecutive coronary arteriograms, 12 patients (all men) had coronary artery ectasia. Ectasia was found most frequently in the circumflex or right coronary artery. Only 1 patient had ectasia in the left anterior descending coronary artery. In 11 patients, ectasia of one artery was associated with severe stenosis or occlusion of other vessels, typical of arteriosclerosis. Histology from an ectatic segment in one of this group showed changes of severe arteriosclerosis with extensive intimal fibrosis and destruction of the media. One patient had a mixed collagen vascular disease. Measurement of coronary sinus flow in 2 patients with coronary artery ectasia showed flows in the range of patients with non-ectatic coronary artery disease. At cardiac surgery flows down the graft to ectatic arteries were in the same range as in grafts to non-ectatic vessels. Patients with coronary artery ectasia should be anticoagulated.

Adult↗