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Biomedical subjects

D Watkins

Publications and source records attributed to D Watkins.

At least 19 recordsLinked to original sources
PubMed2000

Viremia control following antiretroviral treatment and therapeutic immunization during primary SIV251 infection of macaques.

Prolonged antiretroviral therapy (ART) is not likely to eradicate human immunodeficiency virus type I (HIV-I) infection. Here we explore the effect of therapeutic immunization in the context of ART during primary infection using the simian immunodeficiency virus (SIV251) macaque model. Vaccination of rhesus macaques with the highly attenuated poxvirus-based NYVAC-SIV vaccine expressing structural genes elicited vigorous virus-specific CD4 + and CD8+ T cell responses in macaques that responded effectively to ART. Following discontinuation of a six-month ART regimen, viral rebound occurred in most animals, but was transient in six of eight vaccinated animals. Viral rebound was also transient in four of seven mock-vaccinated control animals. These data establish the importance of antiretroviral treatment during primary infection and demonstrate that virus-specific immune responses in the infected host can be expanded by therapeutic immunization.

Animals↗
PubMed2000

T-cell epitopes in variable segments of Chlamydia trachomatis major outer membrane protein elicit serovar-specific immune responses in infected humans.

We previously identified 18 stimulatory Chlamydia trachomatis major outer membrane protein (MOMP) peptides containing at least 23 epitopes presented with various HLA class II allotypes. Only one peptide contained an epitope localized in a variable segment (VS2). Continued studies reported here identified a total of five VS peptides containing T-cell epitopes that are distributed among MOMPs VS1, VS2, and VS4. Only MOMP-primed T-cell cultures from subjects infected with serovar E responded to the serovar E VS peptides, while the response of such cultures to constant-segment peptides was independent of the infecting serovar. Furthermore, MOMP-primed T cells proliferated in response only to the VS peptides encoded in serovar E but not to the corresponding peptides derived from serovar F, I, or J, confirming that these responses were serovar specific.

Amino Acid Sequence↗
PubMed2000

Complementation studies in the cblA class of inborn error of cobalamin metabolism: evidence for interallelic complementation and for a new complementation class (cblH).

AIM: To investigate genetic heterogeneity within the cblA class of inborn error of cobalamin metabolism. CONTEXT: The cblA disorder is characterised by vitamin B12 (cobalamin) responsive methylmalonic aciduria and deficient synthesis of adenosylcobalamin, required for activity of the mitochondrial enzyme methylmalonyl CoA mutase. The cblA gene has not been identified or cloned. We have previously described a patient with the clinical and biochemical phenotype of the cblA disorder whose fibroblasts complemented cells from patients with all known types of inborn error of adenosylcobalamin synthesis, including cblA. METHODS: We have performed somatic cell complementation analysis of the cblA variant fibroblast line with a panel of 28 cblA lines. We have also performed detailed complementation analysis on a panel of 10 cblA fibroblast lines, not including the cblA variant line. RESULTS: The cblA variant line complemented all 28 cell lines of the panel. There was evidence for interallelic complementation among the 10 cblA lines used for detailed complementation analysis; no cell line in this panel complemented all other members. CONCLUSIONS: These results strongly suggest that the cblA variant represents a novel complementation class, which we have designated cblH and which represents a mutation at a distinct gene. They also suggest that the cblA gene encodes a protein that functions as a multimer, allowing for extensive interallelic complementation.

Alleles↗
PubMed2000

The role of repetition in the processes of memorising and understanding: a comparison of the views of German and Chinese secondary school students in Hong Kong.

BACKGROUND: Previous research has found that students and teachers in countries of the Far East often see memorization and understanding as working together to produce higher quality outcomes. In contrast, in the West it is more common to associate memorizing with 'surface' and understanding with 'deep' approaches to learning. AIM: The main purpose of this study was to explore and describe the experiences of the role of repetition in the processes of memorizing and understanding among students with Western (German) and Asian (Chinese) backgrounds. In particular, we were interested in finding indications of possible cultural differences in the experiences of the two ethnic groups. SAMPLE: The participants were 48 Chinese (HKC) and 18 German senior secondary school students in Hong Kong. METHOD: The study used a qualitative research approach. Data were gathered by semi-structured in-depth interviews. Interview transcripts were analysed in order to uncover, categorize and describe the variation of experiences and conceptions of the role of repetition. The two ethnic groups were then compared as to how many interviews were found in each category. RESULTS: A similar proportion of both groups remembered being encouraged to recite by their parents, but the HKC students more often said they were made to recite by their primary teachers. While the HKC students focused on the value of the content of these early memories, the German students focused on the value of the activity itself. Moreover, while the German students tended to downplay the role of repetition in the process of understanding, the HKC students sometimes emphasized repetition combined with 'attentive effort'. By such effort they tried to discover new meanings in the materials studied, in order to deepen their understanding. CONCLUSION: While the findings of this study cannot be considered definitive, it is suggested that the emphasis on attentive effort among HKC students is consistent with a traditional, Confucian perspective on learning. The results also indicate that 'the intention to both memorize and understand', found in previous investigations of the study approaches of HKC students, may arise out of being simultaneously aware of two possibilities inherent in repetition: creating a deep impression on the mind and discovering new meaning. Finally, it is argued that the differences between the two ethnic groups are consistent with earlier research findings that Chinese, unlike Western, students tend to consider effort attributions more salient than ability attributions.

Adolescent↗
PubMed1999

Induction of HLA class I-restricted CD8+ CTLs specific for the major outer membrane protein of Chlamydia trachomatis in human genital tract infections.

HLA class I-restricted CD8+ CTLs specific for the major outer membrane protein (MOMP) of Chlamydia trachomatis are present in the peripheral blood of humans who acquired genital tract infections with the organism. Three HLA-A2-restricted epitopes and two HLA-B51-restricted epitopes were identified in serovar E-MOMP. One of the five epitopes spans a variable segment of MOMP and is likely a serovar E-specific epitope. The other four epitopes are localized in constant segments and are C. trachomatis species specific. CTL populations specific for one or more of the four constant segment epitopes were isolated from all 10 infected subjects tested, regardless of infecting serovars, but from only one of seven uninfected subjects tested. The CTLs failed to recognize corresponding peptides derived from Chlamydia pneumoniae MOMP, further suggesting that they indeed resulted from genital tract infections with C. trachomatis. Significantly, ME180 human cervical epithelial cells productively infected with C. trachomatis were killed by the MOMP peptide-specific CTLs. Further investigations of the ability of such CTLs to lyse normal infected epithelial cells and their presence at inflamed sites in the genital tract will help understand the protective or pathological role of CTLs in chlamydial infections. The MOMP CTL epitopes may be explored as potential components of a subunit vaccine against sexually transmitted diseases caused by C. trachomatis. Moreover, the knowledge provided here will facilitate studies of HLA class I pathways of chlamydial Ag processing and presentation in physiologically relevant human APCs.

Bacterial Outer Membrane Proteins↗
PubMed1999

Adherence of enamel matrix derivatives on root-end filling materials.

It was recently shown that application of enamel matrix derivatives (EMDs) on denuded root dentin promotes periodontal regeneration. EMD is shown to adhere to the etched dentin, but its adherence to root-end filling materials is not known. The purpose of this study was to evaluate the adherence of a commercially available EMD product to root-end filling materials. Dentin sections were embedded in blocks made of acrylic resin. Cavities were prepared in similar acrylic resin blocks and were filled with amalgam, IRM, or composite resin. EMD was labeled with radioactive iodine and applied to the surfaces of the dentin sections, freshly made fillings, or acrylic resin controls. The specimens were rinsed, and the amount of radioactive iodine was determined in a gamma counter. Substantial amounts of EMD adhered to dentin sections. EMD adherence to amalgam and IRM was significantly less than to dentin or composite resin.

Cementogenesis↗
PubMed1999

Identification of DRB alleles in rhesus monkeys using polymerase chain reaction-sequence-specific primers (PCR-SSP) amplification.

Major histocompatibility complex (MHC) class In molecules play a vital role in the regulation of T-cell functions in the mammalian immune system. Two key features characterize the polymorphism of MHC haplotypes in humans and non-human primates: the existence of a large number of alleles, and the high degree of genetic diversity between those alleles. Rhesus monkeys and Chimpanzees have been extensively used as relevant models for human diseases and transplantation We have investigated DRB genes in 19 macaques, members of 3 families, using polymerase chain reaction with sequence-specific primers (PCR-SSP) and denaturing gradient gel electrophoresis (DGGE). After amplification PCR products were purified and subjected direct sequencing. Seven animals (Madison #1) were typed by DDGE also. We report that the DRB haplotypes defined by PCR-SSP exhibit a high degree of concordance with the data obtained by DGGE and direct sequening. Our data show prominent variability in the number of DRB1 alleles ranging from 1-4 per genotype within these families. This analysis demonstrated that most of the amplicons were identical to Mamu-DRB alleles that our PCR primers were to amplify. However, 98-99% similarity was noticed in the case of Mamu-DRB1*0303, Mamu-DRB6*0103 and Mamu-DRB*W201 alleles. The observed mismatches were located in non-polymorphic regions. Thus, family studies in rhesus macaques performed by molecular methods confirmed the multiplicity of Mamu-DRB1 alleles per haplotype and the existence of allelic associations published earlier. In addition, we propose 3 more DRB allele associations (haplotypes): Mamu-DRB1*04-DRB5*03; Mamu-DRB1*04-*DRB*W5; Mamu-DRB1*04*W2. The proposed medium-resolution PCR-SSP technique appears to be a highly reproducible and discriminatory typing method for detecting polymorphisms of DRB genes in rhesus monkeys.

Alleles↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗