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Biomedical subjects

D Watkins

Publications and source records attributed to D Watkins.

At least 37 records · Page 2Linked to original sources

Self-concepts of mountain children of Nepal.

The authors explored the basis of the self-concepts of young children from impoverished villages high in the mountains of Nepal by having them respond to the How I See Myself questionnaire (A. Juhasz, 1985). The participants were 101 children, 7 to 14 years old, from the Sherpa and Tamang ethnic groups. The results provide evidence for questioning the appropriateness of the content of Western self-esteem instruments for such children. The authors argue that items about satisfying basic physical needs may be most appropriate for assessing the self-esteem of such children.

Adolescent↗

Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria.

Methionine synthase catalyzes the remethylation of homocysteine to methionine via a reaction in which methylcobalamin serves as an intermediate methyl carrier. Over time, the cob(I)alamin cofactor of methionine synthase becomes oxidized to cob(II)alamin rendering the enzyme inactive. Regeneration of functional enzyme requires reductive methylation via a reaction in which S-adenosylmethionine is utilized as a methyl donor. Patients of the cblE complementation group of disorders of folate/cobalamin metabolism who are defective in reductive activation of methionine synthase exhibit megaloblastic anemia, developmental delay, hyperhomocysteinemia, and hypomethioninemia. Using consensus sequences to predicted binding sites for FMN, FAD, and NADPH, we have cloned a cDNA corresponding to the "methionine synthase reductase" reducing system required for maintenance of the methionine synthase in a functional state. The gene MTRR has been localized to chromosome 5p15.2-15.3. A predominant mRNA of 3.6 kb is detected by Northern blot analysis. The deduced protein is a novel member of the FNR family of electron transferases, containing 698 amino acids with a predicted molecular mass of 77,700. It shares 38% identity with human cytochrome P450 reductase and 43% with the C. elegans putative methionine synthase reductase. The authenticity of the cDNA sequence was confirmed by identification of mutations in cblE patients, including a 4-bp frameshift in two affected siblings and a 3-bp deletion in a third patient. The cloning of the cDNA will permit the diagnostic characterization of cblE patients and investigation of the potential role of polymorphisms of this enzyme as a risk factor in hyperhomocysteinemia-linked vascular disease.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

The relationship between duration of physical therapy services in the acute care setting and change in functional status in patients with lower-extremity orthopedic problems.

BACKGROUND AND PURPOSE: This study examined the relationship between the duration of physical therapy and functional status at discharge. SUBJECTS: The subjects were 173 inpatients, with a mean age of 67.9 years (SD = 20.5, range = 18-101), referred to physical therapy with lower-extremity orthopedic problems. METHODS: For this retrospective cohort study, medical and physical therapy quality assurance records were used. Functional status, at initiation of and discharge from physical therapy, was measured using the Acute Care Index of Function (ACIF). The ACIF scores, which ranged from 0 to 100, were obtained from quality assurance records. The duration of physical therapy was the number of minutes of physical therapy billed to each patient, as determined from billing records. RESULTS: Subjects received an average of 238.5 minutes of physical therapy (SD = 153.6, range = 15-1,110). Function improved an average of 15.4 points (SD = 17.0, range = -27.4 to 64.9), and the duration of physical therapy was an important predictor of functional status at discharge after controlling for age, length of hospitalization, number of diagnoses, and initial functional status. CONCLUSION AND DISCUSSION: This study provides evidence that the amount of physical therapy that patients with some types of orthopedic problems receive is directly related to the functional improvement that occurs during hospitalization in an acute care setting.

Exercise Therapy↗

Cobalamin metabolism in methionine-dependent human tumour and leukemia cell lines.

OBJECTIVE: To identify the defect in cobalamin metabolism in the human melanoma cell line MeWoLC1, and to determine how frequent this defect is in other methionine-dependent tumour cell lines. DESIGN: Biochemical and somatic cell genetics study. INTERVENTIONS: Aspects of cobalamin metabolism were measured in a panel of 14 human tumour cell lines that were unable to proliferate normally in medium in which methionine had been replaced by its metabolic precursor homocysteine (methionine-dependent cell lines). RESULTS: The human melanoma cell line MeWoLC1 was unique among these cell lines, in that it was characterized by decreased uptake of cobalamin, decreased synthesis of coenzyme derivatives, and decreased functional activity of the cobalamin-dependent enzymes methionine synthase and methylmalonylCoA mutase. This phenotype was identical to that observed in fibroblasts from patients with the cblC and cblD inborn errors of cobalamin metabolism. The defect in cobalamin metabolism in MeWoLC1 was complemented in somatic cell complementation analysis by cblA, cblB, cblD, cblE and cblG fibroblasts, but not by cblC fibroblasts, strongly suggesting that the defect in this cell line affects the cblC locus. Similar changes in cellular cobalamin metabolism were not seen in any other methionine-dependent cell line in the panel, suggesting that there may be multiple causes of methionine dependence, and that inactivation of the cblC locus may not be a common cause of this phenotype in transformed cells. CONCLUSIONS: The defect underlying methionine dependence in MeWoLC1 appears to involve the locus that is affected in patients with the cblC inborn error of metabolism. This defect does not seem to be common among other methionine-dependent cell lines.

Carbon Radioisotopes↗

Polymorphism of the HLA-DRB1 locus in Colombian, Ecuadorian, and Chilean Amerinds.

We have characterized the DRB1 genotypes in a sample of 64 South American Indians drawn from populations in Chile, Colombia, and Ecuador. No novel DRB1 alleles were found in the total of 17 different alleles characterized, indicating that rapid allelic generation does not occur at the DRB1 loci, in contrast to HLA-B. Comparison between Chilean and Colombian/Ecuadorian samples revealed no major differences in their allelic frequencies. In the combined Amerind sample the HLA-DRB1*0407 and HLA-DRB1*1402 alleles occurred in the highest frequencies (38% and 22%, respectively). Genetic distance measurement showed the HLA-DRB1 frequencies reported here to agree with findings in other Amerind groups. The high frequencies of both HLA-DRB1*0407 and HLA-DRB1*1602 alleles, in conjunction with their absence in Siberian samples, suggest that migratory groups other than Siberians may have been involved in the peopling of the Americas.

Alleles↗

FN18-CRM9 immunotoxin promotes tolerance in primate renal allografts.

BACKGROUND: Transplant tolerance, rather than immunity, may be favored in the setting of a lower mature lymphoid mass in the recipient induced by anti-T cell agents. A novel immunosuppressive agent, FN18-CRM9, known to specifically kill T cells with great potency, was evaluated in a transplant model. METHODS: In order to ablate recipient T cells, the immunotoxin FN18-CRM9 was administered to rhesus monkey recipients of MHC-mismatched renal allografts. Donor lymphocytes were injected intrathymically into some animals. RESULTS: All monkeys with T-cell depletion by immunotoxin had prolonged allograft survival, and tolerance confirmed by skin grafting has been confirmed in five of six long-surviving recipients. CONCLUSIONS: In this clinically relevant model, profound but transient T-cell depletion by a single agent substantially promotes tolerance.

Animals↗

Assessing the learning processes of black South African students.

Data based on responses of 126 male and 201 female 14- and 15-year-old Black South African secondary school students showed the Learning Process Questionnaire (LPQ; Biggs, 1987) to be fairly reliable and factorially valid. Comparison with the LPQ means for like-aged students from Australia and Hong Kong called into question the common assertion that Black South African students are more prone to use superficial learning processes than are Western students. In particular, the South African responses to the LPQ indicated that they were less shallow and more oriented toward achievement in their approach to learning than the Australian students were.

Achievement↗

Age and gender differences in the self-esteem of Chinese children.

A Chinese version of the Self-Description Questionnaire 1 (SDQ-1; Marsh, 1988) was used to investigate age and gender differences in a sample of 303 male and 296 female 10-year-old children and 116 male and 116 female 13-year-old children attending typical Beijing public schools. Significant Age x Gender interaction effects were found on all 8 SDQ-1 scales. Main effects for age were found on the Physical Abilities, Reading, and School subscales and for gender on the same three subscales plus Peer Relations. Further analysis indicated that the older girls tended to report significantly lower self-esteem than both the younger girls and older boys in the areas of physical abilities, reading, mathematics, and general self-concept. The boys reported more positive self-perceptions on most nonacademic self-scales, but both the older boys and older girls reported less favorable self-esteem than their younger peers on the scales for reading and school in general.

Adolescent↗

Culture and spontaneous self-concept among Filipino college students.

Responses of 157 Filipino college students to the Twenty Statements Test (TST) were analyzed for content and compared with earlier responses to the TST by U.S. and Hong Kong Chinese college students. Despite the supposedly collectivist nature of the Filipino culture, far fewer Filipino students than U.S. and Hong Kong Chinese students described themselves in terms of social roles. Contrary to theoretical claims, the Filipinos made greater use of the global identity category than did either the U.S. or Hong Kong Chinese students. Evidence also supported the cross-cultural validity of 4 of the Big Five (McCrae & Costa, 1988) personality traits. However, there are questions about the relevance of Openness to Experience to any of these three cultures. Moreover, the finding that the Filipino respondents reported a higher percentage of positive self-descriptions than did either the U.S. or Chinese respondents indicated that such differences cannot be explained in terms of the individualism-collectivism dimension.

Adolescent↗

Loss of heterozygosity on chromosome 22 in human gliomas does not inactivate the neurofibromatosis type 2 gene.

The molecular genetic alterations that underlie development of gliomas, the most common neoplasm of the human central nervous system, include activation of cellular proto-oncogenes as well as inactivation of tumor suppressor genes. Although research has identified some affected loci, others clearly remain to be identified. We have investigated loss of heterozygosity on chromosome 22 in a panel of sporadic gliomas, and have assessed the possibility that inactivation of the neurofibromatosis type 2 (NF2) tumor suppressor gene on 22q plays a role in development of sporadic gliomas in humans. Loss of heterozygosity for loci on chromosome 22 loci was observed in 15 of 47 informative blood-tumor pairs, although no common area of loss of heterozygosity shared by all of these tumors could be identified. The most frequently affected segment, distal to the NF2 locus and bounded proximally by D22S15 and distally by a gene for myoglobin, was shared by as many as 11 tumors. Loss of heterozygosity at the NF2 locus was observed in 10 tumors. No rearrangements of the NF2 gene could be detected by Southern analysis of restriction endonuclease-digested genomic DNA, and no abnormally migrating bands were detected on single strand conformation analysis of individual exons of the NF2 gene. Thus, although frequent loss of heterozygosity on chromosome 22 suggests that inactivation of a tumor suppressor gene on this chromosome plays a role in development of gliomas, there is no evidence that inactivation of the NF2 gene is implicated in this process, confirming the results of other studies of the NF2 gene in human gliomas. The identity of the putative tumor suppressor gene on 22q involved in development of gliomas remains unknown.

Brain Neoplasms↗

Registration and immobilization in robot-assisted surgery.

Robotic systems for computer-assisted surgery involve both tools and techniques that are new to the surgical arena. Registration and immobilization in particular are key problems. Registration is the spatial alignment of the coordinate frames of the robot, an anatomic object (e.g., a bone), and the preoperative plan (a computer model). Immobilization is necessary to maintain that alignment. We discuss various approaches to registration and immobilization and solutions appropriate for an orthopedic surgical system.

Ankle Joint↗

Visualization of beta-adrenoceptor binding sites on human inferior vagal ganglia and their axonal transport along the rat vagus nerve.

DESIGN: Because of uncertainties regarding the complete antihypertensive mechanism of action of beta-adrenoceptor antagonists, the present study determined whether vagal afferent neurons of humans and rats possess beta-adrenoceptors. Such a location would provide an appropriate target for beta-blockers to modulate neurotransmission of barosensitive neurons, thereby affecting blood pressure. Therefore, in vitro receptor autoradiography of high-affinity beta-adrenoceptor binding sites was performed on slices of human and rat inferior vagal (nodose) ganglia with [125I]-pindolol. METHODS: Slide-mounted sections of human and rat inferior vagal ganglia were incubated with [125I]-pindolol in the absence or presence of propranolol (10 mumol/l) to define non-specific binding, atenolol (10 mumol/l) to inhibit binding to beta 1-adrenoceptors, or ICI 118551 (3 nmol/l) to inhibit binding to beta 2-adrenoceptors. Unilateral vagal ligation was also performed in the rat to study whether beta-adrenoceptors are subject to axonal transport along the vagus nerve. RESULTS: [125I]-pindolol bound with > 90% specific binding to sections both of human and of rat inferior vagal ganglia. Specific binding occurred over both neuronal perikarya and nerve fibres. In both species the beta 2-adrenoceptor subtype appeared to predominate, as defined by the differential ability of ICI 118551 (beta 2) and atenolol (beta 1) to inhibit the binding of [125I]-pindolol. Furthermore, unilateral vagal ligation in the rat caused an accumulation of specific binding adjacent to the ligature sites. CONCLUSIONS: We conclude that human and rat vagal afferent (and efferent) neurons possess beta-adrenoceptors that potentially could explain the mechanism of action of beta-adrenoceptor antagonists in the therapy of hypertension.

Animals↗

Linkage analysis of the nail-patella syndrome.

Nail-patella syndrome (NPS) is an autosomal dominant disorder characterized by dysplasia of nails and patella, decreased mobility of the elbow, iliac horns, and, in some cases, nephropathy. The disorder has been mapped to the long arm of chromosome 9, but the precise localization and identity of the NPS gene are unknown. Linkage analysis in three NPS families, using highly informative dinucleotide repeat polymorphisms on 9q33-q34, confirmed linkage of NPS to this chromosome. Recombinations were detected, by two-point linkage analysis, between NPS and the centromeric markers D9S60 and the gelsolin gene and the telomeric markers D9S64 and D9S66, in one of the families. Haplotype analysis suggested an additional recombination between NPS and the argininosuccinate synthetase (ASS) gene. These results localize the NPS gene to an interval on 9q34.1, distal to D9S60 and proximal to ASS, comprising a genetic distance of approximately 9 cM. This represents a significant refinement in the localization of the NPS gene.

Chromosome Mapping↗

Analysis of oncogene expression in primary human gliomas: evidence for increased expression of the ros oncogene.

Expression of a panel of oncogenes and potential oncogenes was studied in normal human brain and in 17 human gliomas, including three low- and 14 high-malignancy-grade tumors. PolyA RNA was isolated from glioma biopsies and used as template for reverse transcriptase-catalyzed synthesis of radioactively labeled cDNA. Labeled cDNA was then hybridized to filters to which probes for various oncogenes had been attached. Increased signal intensity, as compared with that of normal brain, was observed for the ros oncogene in six of 17 gliomas, including gliomas of both low and high malignancy grades. Increased ros expression was verified by Northern blot analysis in one tumor. These results suggest that increased ros expression may play a role in tumorigenesis in a significant proportion of gliomas. Increased expression of other genes, including the erbA2, mel, and ets oncogenes was observed in a smaller proportion of the gliomas tested, suggesting a possible role for these oncogenes in individual tumors but no generalized role in development or progression of human gliomas.

Adult↗

A method for calculating the spinal-cord depth from an oblique simulator radiograph.

An equation for calculating the spinal-cord depth from a simulator radiograph taken at an oblique angle has been derived. This equation is very useful when the cord cannot easily be identified on a horizontal lateral radiograph as in the case of the lower neck and upper thorax. To use this equation one needs to know the following parameters: the source-Axis-Distance, vertical source-skin-distance, the gantry angle at which the film was taken, and the target-film-distance.

Humans↗

Genetics, prognosis and therapy of central nervous system tumors.

Tumors of the central nervous system (CNS) are common causes of morbidity and mortality. These tumors can occur sporadically or in individuals with genetic disorders predisposing to cancer development. Such syndromes include neurofibromatosis type 2, neurofibromatosis type 1, Li-Fraumeni syndrome, as well as von Hippel-Lindau disease, tuberous sclerosis, and Turcot syndrome. There may also be familial syndromes resulting in glioma or meningioma alone, but these are not well understood. Development of sporadic gliomas is accompanied by a number of molecular genetic alterations, including activation of dominant oncogenes and inactivation of tumor suppressor genes. Some of these alterations may be associated with progression of gliomas to their most malignant form, glioblastoma multiforme. However, at this time molecular genetic analysis of gliomas does not provide better prognosis than histopathological staging. Recently, experimental treatments of gliomas in rodents, using gene therapy, have been reported. Results of these studies have been promising, and these techniques may represent a future direction for therapy in humans.

Central Nervous System Neoplasms↗