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Biomedical subjects

M L Thomas

Publications and source records attributed to M L Thomas.

At least 109 records · Page 6Linked to original sources
PubMed1993

Bone disease in burn patients.

Burn patients are at risk for bone disease due to aluminum (Al) exposure from use of antacids and albumin, partial immobilization, and increased production of endogenous glucocorticoids. Moreover, severely burned children are growth impaired up to 3 years after the burn. To determine the extent of bone disease, we studied nine men and three women, ages 18-41 years, with greater than 50% body surface area burn. Seven patients underwent iliac crest bone biopsy following double tetracycline labeling, one additional patient expired after a single label, and three others had postmortem specimens obtained for quantitative Al only. Serial serum and urine samples were obtained weekly until biopsy or death. All biopsied patients had reduced bone formation and osteoid area, surface, and width, with mineral apposition rate, osteoblast surface, and osteoclast number with normal eroded surfaces compared to age- and sex-matched normal ambulatory volunteers. Burn patients also had reduced bone formation, mineral apposition rate, osteoid area, and surface compared to age-matched volunteers at short-term bed rest. Serum levels of osteocalcin were low. Most patients had mild hypercalcemia but only a third had hypercalciuria. All patients had elevated Al in blood or urine; urine Al correlated inversely with serum osteocalcin. In 60% significant bone Al was detectable by stain or quantitation. Our data are compatible with burn patients having markedly reduced bone turnover. Al loading, partial immobilization, endogenous corticosteroids, and cytokine production may be among the etiologic factors.

Adolescent↗
PubMed1993

Leukocyte common antigen-related phosphatase (LRP) gene structure: conservation of the genomic organization of transmembrane protein tyrosine phosphatases.

The leukocyte common antigen-related protein tyrosine phosphatase (LRP) is a widely expressed transmembrane glycoprotein thought to be involved in cell growth and differentiation. Similar to most other transmembrane protein tyrosine phosphatases, LRP contains two tandem cytoplasmic phosphatase domains. To understand further the regulation and evolution of LRP, we have isolated and characterized mouse lambda genomic clones. Thirteen genomic clones could be divided into two non-overlapping clusters. The first cluster contained the transcription initiation site and the exon encoding most of the 5' untranslated region. The second cluster contained the remaining exons encoding the protein and the 3' untranslated region. The gene consists of 22 exons spanning over 75 kb. The distance between exon 1 and exon 2 is at least 25 kb. Characterization of the 5' ends of LRP mRNA by S1 nuclease protection identifies putative initiation start sites within a G/C-rich region. The upstream region does not contain a TATA box. Comparison of the LRP gene structure to the mammalian protein tyrosine phosphatase gene, CD45, shows striking similarities in size and genomic organization.

Amino Acid Sequence↗
PubMed1993

The leukocyte common antigen, CD45 and other protein tyrosine phosphatases in hematopoietic cells.

Numerous protein tyrosine phosphatases have been characterized that are expressed by hematopoietic-derived cells. CD45, a transmembrane protein tyrosine phosphatase expressed by all nucleated cells of hematopoietic origin, has been a prototype for studying the function of these enzymes. In T lymphocytes, CD45 serves to dephosphorylate and activate members of the Src-tyrosine kinase family. Without CD45 function, T cells cannot respond to antigen. Therefore, CD45 functions positively to regulate lymphocyte activation. The characteristics of other protein tyrosine phosphatases found in hematopoietic-derived cells suggests that they are also essential in regulating cell differentiation and activation.

Animals↗
PubMed1993

Predictors of concerns and coping strategies of cancer chemotherapy outpatients.

The purpose of this study was to determine predictor variables of the number of concerns and coping strategies of cancer patients during a 6-month period of chemotherapy. The adult patients (N = 64) were diagnosed with selected types of cancer. Patients kept logs in which they recorded concerns and strategies for managing those concerns. Three significant predictors of patients who experienced greater numbers of concerns were identified. Patients with less vigor-activity, less of an internal locus of control, and who perceived the goal of their chemotherapy treatment to be curative reported greater concerns. These factors explained 55% of the total variance in the number of concerns. No significant predictors of coping strategies were obtained.

Adaptation, Psychological↗
PubMed1993

Effects of catecholamine depletion on alertness and mood in rested and sleep deprived normal volunteers.

Alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, was used to evaluate the physiologic role of central nervous system catecholamines in modulating alertness and mood. Forty healthy males were randomized to one of four conditions: AMPT in a rested condition; AMPT plus 40.5 hours of total sleep deprivation; placebo plus sleep deprivation; or placebo in a rested condition. Repeated measures of alertness and mood revealed that treatment with AMPT or sleep deprivation increased sleepiness, and combined treatment produced greater sleepiness than either treatment alone. In contrast, although combined treatment with AMPT and sleep deprivation led to large increases in negative mood, neither treatment alone produced consistent mood changes. These findings are consistent with the view that sleep deprivation is associated with decreased functional catecholamine neurotransmission. Furthermore, mood effects following sleep deprivation plus AMPT suggest that catecholamines may be involved in mood changes during sleep deprivation.

Adult↗
PubMed1993

The presence of functional estrogen receptors in intestinal epithelial cells.

Reproductive and maturational nutritive needs are examples of situations in which alterations in circulating concentrations of estrogens are associated with changes in intestinal epithelial function. However, it is not clear that any of these effects is due to direct interaction of estrogen with intestinal epithelial estrogen receptors (ER). The experiments reported here were designed to determine whether the small intestinal epithelium contains functional ER and might, therefore, be an estrogen-responsive tissue. IEC-6 cells, a non-transformed line of cells isolated from rat small intestinal crypts, were used for many of the experiments, because they provide a pure preparation of crypt epithelial cells. IEC-6 cells were found to exhibit specific saturable binding of estradiol with a Kd of 5 x 10(-10) M and approximately 100 binding sites/cell. Reverse transcriptase-polymerase chain reaction demonstrated that IEC-6 cells as well as epithelial cells from each segment of the rat intestine (duodenum, jejunum, ileum, and colon) contained ER mRNA of the sequence determined from rat uterus. Estradiol was shown to stimulate IEC-6 cell c-fos mRNA content rapidly and transiently in a manner analogous to that which has been previously demonstrated for other estrogen-responsive tissues. These data demonstrate that intestinal epithelial cells contain ER capable of regulating gene transcription and provide the basis for future studies designed to elucidate the role of estrogens in the regulation of intestinal epithelial function and pathophysiology.

Animals↗
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↗