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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

The distribution of atherosclerosis in the lower limbs.

Sixty-seven consecutive aortograms in non-diabetic patients were studied to establish the distribution of atherosclerosis in the arteries of 134 lower limbs. Prolonged filming and multiple exposures of the feet showed ankle vessels in 131 of the limbs (98%) and a pedal arch or collaterals in 126 (93%). In 51% of the limbs at least one of the calf arteries was occluded and only 24% had two patent arteries at ankle level. The pedal arch was complete in only 16%. The patency rate of the pedal arch was similar in all three symptom groups (p greater than 0.05). Two separate analyses were performed. The first was based on symptoms. Critical ischaemia was present in 18 limbs (13%), claudication in 69 limbs (52%) and 47 limbs were symptomless (35%). The second analysis was based on the sites of major occlusion. Occlusions were already present in 81% of the symptomless limbs, predominantly in the distal vessels. In limbs with claudication or critical ischaemia there were more occlusions above the knee (77 and 89%, respectively) than in limbs without symptoms (36%) (chi 2 = 27.60, p less than 0.001). Occlusion of the popliteal artery was significantly more frequent in the patients with symptoms of critical ischaemia (50%) than in either of the other two groups (chi 2 = 15.61, p less than 0.001). Atherosclerosis appears to develop in the small vessels of the calf and foot at an early stage. The extent of this involvement may influence the progression of symptoms and the outcome of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Outpatient chemotherapy: patients' and family members' concerns and coping strategies.

Since the majority of cancer chemotherapy is given on an outpatient basis, it is important for nurses in the community to understand the concerns that patients and family members experience during the treatment and how they manage these concerns. The 64 adult patients were diagnosed with selected solid tumors or lymphoma and were initiating a course of chemotherapy. Sixty-nine family members participated as well. Each participant kept a log in which to record concerns and strategies taken to manage them. Patients reported fewer concerns than their families, but both had similar concerns and rated them as high in intensity. Patients performed more strategies than family members, but both rated the effectiveness of their strategies as moderately high and cited themselves as the sources of the strategies.

Adaptation, Psychological↗
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↗
PubMed1991

Protein tyrosine phosphatase domains from the protochordate Styela plicata.

Protein tyrosine phosphorylation is an important regulatory mechanism in cell physiology. While the protein tyrosine kinase (PTKase) family has been extensively studied, only six protein tyrosine phosphatases (PTPases) have been described. By Southern blot analysis, genomic DNA from several different phyla were found to cross-hybridize with a cDNA probe encoding the human leukocyte-common antigen (LCA; CD45) PTPase domains. To pursue this observation further, total mRNA from the protochordate Styela plicata was used as a template to copy and amplify, using polymerase chain reaction (PCR) technology, PTPase domains. Twenty-seven distinct sequences were identified that contain hallmark residues of PTPases; two of these are similar to described mammalian PTPases. Southern blot analysis indicates that at least one other Styela sequence is highly conserved in a variety of phyla. Seven of the Styela domains have significant similarity to each other, indicating a subfamily of PTPases. However, most of the sequences are disparate. A comparison of the 27 Styela sequences with the ten known PTPase domain sequences reveals that only three residues are absolutely conserved and identifies regions that are highly divergent. The data indicate that the PTPase family will be equally as large and diverse as the PTKases. The extent and diversity of the PTPase family suggests that these enzymes are, in their own right, important regulators of cell behavior.

Amino Acid Sequence↗
PubMed1991

Calcium metabolism and bone mineralization in female rats fed diets marginally sufficient in calcium: effects of increased dietary calcium intake.

Experiments were carried out to determine the ability of female rats with poorly mineralized skeletons to increase bone mineralization in response to increased dietary Ca consumption. We specifically addressed this question with regard to two different periods of the life cycle: the period of sexual maturation (6-9 weeks of age), and in animals that had attained adult rates of skeletal mineralization (100 days of age). We found that at both stages, increased dietary Ca consumption resulted in increased trabecular bone volume and total bone Ca. In the younger animals, it was found that dietary history influenced the disposition of bone mineral. Animals that were initially Ca-deprived exhibited increased trabecular bone and decreased cortical thickness compared to animals continuously fed 0.5% Ca. Ovariectomy of mature animals reduced but did not eliminate the response to increased Ca intake.

Aging↗
PubMed1991

Characterization and expression of the human leukocyte-common antigen (CD45) gene contained in yeast artificial chromosomes.

The leukocyte-common antigen (CD45) is a transmembrane protein tyrosine phosphatase expressed uniquely by cells of hematopoietic origin. There are multiple isoforms of CD45 that are generated by the variable use of three exons (exons 4-6). The use of the variable exons results in changes near the amino-terminus of the mature glycoprotein. The gene is located on chromosome 1 for both human and mouse in a region that is homologous between these two species. This conserved linkage group contains a number of genes of immunological interest, such as the genes for complement regulatory proteins and the FCG2 receptor. Yeast artificial chromosomes provide a vector system in which large fragments of foreign DNA can be isolated and are suited to long-range physical mapping. To this end, three yeast artificial chromosomes containing the human CD45 gene have been isolated and characterized. They overlap to span 475 kb, establishing the largest physical map for DNA within the conserved linkage group. The CD45 gene is entirely encoded within one yeast artificial chromosome clone as determined by mapping with cDNA probes. A mouse B cell line transfected with this YAC clone expressed the low-molecular-weight isoform of the protein into the cell surface. The size of the human CD45 gene was determined to be approximately 120 +/- 10 kb.

Animals↗
PubMed1991

The distribution of recurrent varicose veins: a phlebographic study.

One hundred consecutive legs in 74 patients presenting with recurrent varicose veins were investigated by varicography. Forty recurrences occurred at the groin, 80 in the thigh and 97 in the calf. Within each group different anatomical variations were encountered, and we describe the frequency of these and of certain commonly observed combinations. We also suggest possible causes, and discuss how the results of varicography may assist in surgical management.

Adult↗
PubMed1991

Novel plasmid combinations in Haemophilus ducreyi isolates from Thailand.

Thirty isolates of Haemophilus ducreyi collected in Thailand in 1984 were characterized by plasmid content. Three novel plasmids with estimated molecular masses of 1.8, 2.6, and 2.8 MDa were observed in 29 isolates, in addition to the 3.2-, 5.7-, and 7.0-MDa beta-lactamase and 4.4-MDa sulfonamide resistance plasmids. At least three of the seven plasmids were observed in each of the 29 isolates. The number and diversity of plasmids observed in these isolates of H. ducreyi distinguish them from strains previously described.

Chancroid↗
PubMed1991

CD8+ T-cell clones deficient in the expression of the CD45 protein tyrosine phosphatase have impaired responses to T-cell receptor stimuli.

CD45 is a high-molecular-weight transmembrane protein tyrosine phosphatase expressed only by nucleated cells of hematopoietic origin. To examine function, mouse CD8+ cytolytic T-cell clones were derived that had a specific defect in the expression of CD45. Northern (RNA) blot analysis indicates that the CD45 deficiency is due to either a transcriptional defect or mRNA instability. The CD45-deficient cells were greatly diminished in their ability to respond to antigen. All functional parameters of T-cell receptor signalling analyzed (cytolysis of targets, proliferation, and cytokine production) were markedly diminished. A CD45+ revertant was isolated, and the ability to respond to antigen was restored. These results support a central and immediate role for this transmembrane protein tyrosine phosphatase in T-cell receptor signalling.

Animals↗
PubMed1991

Calcium uptake by duodenal epithelial cells is increased during lactation.

It is known that duodenal absorption of calcium is increased during lactation, and, more specifically, it has been shown that duodenal active transport of calcium is increased. The energy-requiring step for this active transport process is thought to occur at the basolateral membrane of the duodenal epithelial cells, where calcium is pumped from the cell into the extracellular fluid. The present experiments were carried out to determine whether calcium uptake into duodenal epithelial cells is also altered during lactation. Uptake of 45Ca into isolated duodenal epithelial cells from lactating animals showed markedly enhanced calcium uptake when compared with cells from control animals. Uptake was calcium concentration dependent for both groups. Since duodenal epithelial cells are known to contain increased calbindin9k, a calcium-binding protein, during lactation, calcium uptake was also measured in cells that were preincubated in medium containing calcium. In these experiments, the total 45Ca uptake was reduced, but the difference between lactating and control remained. These experiments show that the uptake of calcium into duodenal epithelial cells is among the components of the transcellular calcium transport process which is enhanced during lactation.

Animals↗
PubMed1990

Tyrosine phosphatase CD45 is essential for coupling T-cell antigen receptor to the phosphatidyl inositol pathway.

Stimulation of T lymphocytes through their antigen receptor (T-cell receptor; TCR) results in the activation of a tyrosine kinase and the generation of phosphatidyl inositol (PtdIns)-derived second messengers. Several reports have indicated that CD45, a haematopoietic cell-specific surface glycoprotein with tyrosine phosphatase activity in its cytoplasmic domain, is important in lymphocyte activation. To examine the possibility that CD45 might influence proximal signal transduction events through the TCR, we have isolated a variant of the human T-cell leukaemic line, HPB-ALL, which fails to express this phosphatase. Unlike cells expressing CD45, stimulation of the TCR in the CD45-negative cell does not result in PtdIns-derived second messengers. Reconstitution of CD45 expression restored early signalling events through the TCR. To localize the site of CD45 action, the human muscarinic type 1 receptor, which also activates the PtdIns second messenger pathway, was transfected into the CD45-negative cell. Although stimulation of the TCR failed to generate PtdIns-derived second messengers, there was normal activity of the PtdIns pathway when human muscarinic receptor type 1 was stimulated, despite the absence of CD45. These data indicate that CD45 influences a cellular component that is essential for effective coupling of the TCR to the PtdIns second messenger pathway.

Antigens, CD↗
PubMed1990

The incidence of popliteal aneurysms in patients with arteriomegaly.

Sixty-five patients with arteriomegaly were investigated by arteriography or digital subtraction angiography, and ultrasound or computed tomography to exclude popliteal aneurysms. In 36 (55%) patients popliteal aneurysms were demonstrated. In view of this high incidence and the known serious complications of popliteal aneurysms, we suggest that all patients with angiographic evidence of arteriomegaly should be further investigated by ultrasound or computed tomography.

Adult↗
PubMed1990

Identification of an additional member of the protein-tyrosine-phosphatase family: evidence for alternative splicing in the tyrosine phosphatase domain.

Protein-tyrosine-phosphatases (protein-tyrosine-phosphate phosphohydrolase, EC 3.13.48) have been implicated in the regulation of cell growth; however, to date few tyrosine phosphatases have been characterized. To identify additional family members, the cDNA for the human tyrosine phosphatase leukocyte common antigen (LCA; CD45) was used to screen, under low stringency, a mouse pre-B-cell cDNA library. Two cDNA clones were isolated and sequence analysis predicts a protein sequence of 793 amino acids. We have named the molecule LRP (LCA-related phosphatase). RNA transfer analysis indicates that the cDNAs were derived from a 3.2-kilobase mRNA. The LRP mRNA is transcribed in a wide variety of tissues. The predicted protein structure can be divided into the following structural features: a short 19-amino acid leader sequence, an exterior domain of 123 amino acids that is predicted to be highly glycosylated, a 24-amino acid membrane-spanning region, and a 627-amino acid cytoplasmic region. The cytoplasmic region contains two approximately 260-amino acid domains, each with homology to the tyrosine phosphatase family. One of the cDNA clones differed in that it had a 108-base-pair insertion that, while preserving the reading frame, would disrupt the first protein-tyrosine-phosphatase domain. Analysis of genomic DNA indicates that the insertion is due to an alternatively spliced exon. LRP appears to be evolutionarily conserved as a putative homologue has been identified in the invertebrate Styela plicata.

Amino Acid Sequence↗