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Biomedical subjects

C A Howard

Publications and source records attributed to C A Howard.

At least 19 recordsLinked to original sources
PubMed2001

The ethical dimensions of cultural competence in border health care settings.

Through thematic stories of patient and provider interactions on the U.S.-Mexico border, this article challenges the commonly understood definition of culture. It explores areas of concern related to cultural competency and medical ethics. Stories outline issues related to communication and comprehension, use of interpreters, gender and sexual orientation, traditional health care practices, socioeconomic status, age, health care settings, and involvement of community representatives. Policy recommendations address language, continuity of care, and health care professions education.

Communication↗
PubMed1997

Industrial Genotoxicology Group collaborative trial to investigate cell cycle parameters in human lymphocyte cytogenetics studies.

Human lymphocyte cultures have been used for many years for assessing the in vitro clastogenic potential of test substances. In these assays the harvest time should be based on the cell cycle time in order to ensure that cells are sampled at an appropriate time for the detection of clastogenic effects. The sources of variation in the cell cycle time in routine cytogenetic assays have not been well studied. Consequently 13 laboratories, all members of the Industrial Genotoxicology Group, participated in a collaborative study to measure the variation in cell cycle time in cultured human peripheral blood lymphocytes under various conditions. The study was performed in two phases, spaced 6 months apart. The average generation time (AGT) was measured by the incorporation of bromodeoxyuridine. Very similar AGTs were found in the presence and absence of S9 mix. The mean AGT (mean of four donors) in each laboratory varied from 11.2 to 17.1 h, indicating there is significant variability in cell cycle times of human peripheral blood lymphocytes between laboratories. There was greater variation between laboratories than within laboratories. A comparison of AGT values at 72 h performed in experiments at least 6 months apart indicated good reproducibility in most laboratories. The study indicates that a 24 h post-treatment harvest may result in the analysis of very few first division cells unless very significant cell cycle delay is induced by the test substance. It was also found that a post-harvest time equivalent to 1.5 cell cycles will result in an approximately equal mixture of first and second division cells and therefore should by suitable for assessing both the induction of chromosome aberrations and polyploidy.

Animals↗
PubMed1996

A simple splenic reticuloendothelial function test: counting erythrocytes with argyrophilic inclusions.

The presently accepted methods for evaluation of splenic reticuloendothelial (RE) function include 99mTc sulfur colloid spleen scan, antibody-coated autologous erythrocyte clearance, and pocked erythrocyte count. All methods involve special equipment and/or risk and inconvenience to patients. A simple method of assessing splenic RE function was developed by counting erythrocytes with argyrophilic inclusions using a simple silver stain and an ordinary microscope. To test the validity of this method, blood samples were collected from patients suspected of having hyposplenia or asplenia, including patients with history of splenectomy, sickle cell disease or trait, and newborns. Blood samples were also collected from normal adults and from patients without hyposplenia or asplenia as controls. The samples were tested by this method and compared to the pocked erythrocyte count that served as a gold standard. The results obtained by the two methods were found to be very comparable with little overlap between those from controls and patients with definite hyposplenia or asplenia. With the pocked erythrocyte count as the gold standard, this method has a sensitivity of 88.9% and a specificity of 97.1%. However, this method requires no special equipment. Staining can be applied to fresh blood smears as well as to Wright-stained smears, and the silver-stained smears are permanent.

Adolescent↗
PubMed1996

Extended harvest times are not necessary for the detection of in vitro clastogens in regulatory cytogenetics studies.

The choice of harvest time in in vitro cytogenetics assays is a critical factor in determining the sensitivity of the assay for detecting clastogenic potential. As yet there is no harmonization of regulatory requirements in this aspect. It has been suggested that the use of extended harvest times can improve the sensitivity of detecting some chemicals which either induce cell cycle delay or produce lesions which induce chromosome aberrations at divisions subsequent to the first post-treatment mitosis. The incidence of such chemicals encountered in the routine testing of chemicals for regulatory submissions is not known. Therefore a large database of 550 chemicals tested in nine laboratories using standard regulatory protocols, including a late harvest time, was assessed for the incidence of chemicals uniquely positive only at a delayed harvest time. The number of such chemicals was very low ( < 0.2%) and the chromosome damage induced by these chemicals may not result from direct genotoxic mechanisms. Based on these data it is recommended that there is no need to include an extended harvest time in in vitro cytogenetics assays except where it might help to resolve an equivocal result.

Animals↗
PubMed1995

Trichloroacetic acid: investigation into the mechanism of chromosomal damage in the in vitro human lymphocyte cytogenetic assay and the mouse bone marrow micronucleus test.

Trichloroacetic acid (TCA) was tested for its ability to induce chromosomal damage in cultured human peripheral blood lymphocytes and in bone marrow cells of male and female C57BL/6JfBL10/Alpk mice. Two in vitro cytogenetic assays were conducted with TCA. In the first TCA, as free acid, was added to whole blood cultures at final concentrations of 500, 2000 and 3500 micrograms/ml in the presence and absence of an auxiliary metabolic activation system (rat liver S9-mix). Statistically significant increases in the percentage of aberrant cells compared with solvent control values were observed in cultures treated with TCA at 2000 and 5000 mu/ml. Investigation into the effects of TCA on the pH of the culture medium revealed significant reductions in pH at both these TCA concentrations. Neutralized TCA was then tested at concentrations of 500, 2,000 and 5000 micrograms/ml, also in the presence and absence of S9-mix. No statistically or biologically significant increases in the percentage of aberrant cells were observed in any of these cultures. In the mouse micronucleus test, neutralized TCA was administered in two equal intraperitoneal doses 24 h apart to C57BL/6JfBL10/Alpk mice (337, 675 and 1080 mg/kg in males; 405, 810 and 1300mg/kg in females). These dose levels represent 25%, 50% and 80% of the median lethal dose (MLD) in this strain of mouse. Bone marrow samples were taken 6 and 24 h after the second dose and the chromosomal damage assessed by analysis of the bone marrow for micronuclei. No statistically or biologically significant increases in the incidence of micronucleated polychromatic erythrocytes compared with the solvent control dosed animals were observed in either sex at the 6 h sampling time or in the females at the 24 h sampling time. A small but statistically significant increase in micronucleated polychromatic erythrocytes was observed in male mice 24 h after a dose of 675 mg/kg (50% MLD). Since no increases were noted at the 25 or 80% MLD, and the levels recorded are within the range of the concurrent solvent control values, the small increase observed in the males at the 50% MLD is considered not to be biologically significant. Flow cytometric studies on suspensions of isolated liver cell nuclei revealed that changes in FITC binding (indicating altered chromatin conformation) were induced by pH changes alone and were not caused by neutralized TCA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Actin-binding protein expression in benign and malignant melanocytic proliferations.

Studies on melanoma cell lines indicate the expression of actin-binding protein (ABP), a peripheral cytoplasmic protein that crosslinks actin, is important for melanoma cell motility. We used an ABP-specific monoclonal antibody to characterize ABP expression in 18 benign nevi and 28 primary and metastatic malignant melanomas. Heterogeneous expression of ABP staining was observed in metastatic melanoma. No clear differences in ABP staining were identified among compound nevi, dysplastic nevi, and superficial spreading melanoma; however, the lentiginous intraepidermal component of the benign and malignant lesions and the pagetoid cells of superficial spreading malignant melanoma were negative for ABP. In contrast, the nested intraepidermal and dermal components of both benign nevi and primary malignant melanoma were positive. The differential expression of ABP of the lentiginous component as opposed to the intraepidermal nests and pagetoid cells of benign nevi or melanoma may represent a capacity of the nested melanocytes to migrate from the epidermis to the dermis during maturation or invasion. Taken together, the findings support that ABP may be important for cell-cell adhesion during tumorigenesis and may play a role in tumor cell ameboid motility during tissue invasion.

Antibodies, Monoclonal↗
PubMed1991

Several testis-expressed genes in the mouse t-complex have expression differences between wild-type and t-mutant mice.

The t-complex of the mouse occupies the proximal half of chromosome 17 and contains genes which have profound effects on spermatogenesis. Mutations of several loci in the t-complex appear to interact to cause male sterility or transmission ratio distortion (TRD). By cDNA screening or chromosomal walking we have identified seven genes, which are expressed in the germ cells of testis and map to various regions of the t-complex. These genes were named t-complex testis-expressed (Tctex) genes. An analysis of their expression patterns in testes from +/+, +/t, and t/t mice was done by in situ hybridization and by northern blotting. Six genes begin to be expressed at the pachytene stage: Three of them are more abundant at pachytene stage, while three others are more abundant at postmeiotic stages. One gene is expressed at all the stages of spermatogenesis. Interestingly, four Tctex genes show differences in the amount of transcript between wild-type and t-mutant testes. The chromosomal location and expression pattern imply that Tctex genes might be candidate genes for sterility or TRD.

Animals↗
PubMed1991

Heritability of ventilatory function in smoking and nonsmoking New Mexico Hispanics.

Familial aggregation of ventilatory function has been described in several populations, but the effects of age and cigarette smoking on the extent of aggregation have not been well characterized. We used data from a survey of a Hispanic population in New Mexico to obtain estimates of heritability for FVC and FEV1 as percentages of predicted value. Product-moment correlations for FVC of spouse pairs were 0.18 (n = 90 pairs) if neither smoked, 0.013 (n = 45 pairs) if only the wife smoked, 0.18 (n = 118 pairs) if only the husband smoked, and -0.04 (n = 83 pairs) if both smoked. Correlations for FEV1 of spouse pairs were similar. Because parent-child correlations did not vary with sex, we calculated product-moment correlations from the pooled data. The parent-child correlations for nonsmoking parents with nonsmoking children 6 to 17 yr of age and living in the same house were 0.16 (n = 335 pairs) and 0.17 for FVC and FEV1, respectively. For parents whose children were 25 yr of age or older, the parent-child correlations for those living in different houses were 0.37 (n = 63 pairs) for FVC and 0.40 for FEV1 if neither smoked, and 0.24 (n = 27 pairs) for FVC and 0.14 for FEV1 if both smoked. Heritability estimates, estimated by path analysis, were 0.43 for FVC and 0.42 for FEV1 if neither family member smoked and 0.65 for FVC and 0.44 for FEV1 if both family members smoked. We conclude that there is a moderate degree of heritability of FVC and FEV1 with no substantial change based on age or smoking status.

Age Factors↗
PubMed1990

The nucleotide excision repair epistasis group in Neurospora crassa.

DNA repair mutants in eucaryotes are normally assigned to three epistasis groups. Each epistasis group represents a "pathway" for DNA repair. The pathways are commonly designated (1) nucleotide excision repair, (2) recombination repair and (3) mutagenic repair. An excision repair epistasis group has been established in Neurospora and the mutants assigned to this group should be limited in their ability to excise pyrimidine dimers and other bulky lesions from DNA. Using a pyrimidine dimer-specific assay, we have found that all Neurospora crassa mutants assigned to the excision repair epistasis group are capable of removing pyrimidine dimers from the DNA at a rate similar to the wild-type organism.

DNA Repair↗
PubMed1990

Genetic and molecular analysis of the proximal region of the mouse t-complex using new molecular probes and partial t-haplotypes.

The t-complex is located on the proximal third of chromosome 17 in the house mouse. Naturally occurring variant forms of the t-complex, known as complete t-haplotypes, are found in wild mouse populations. The t-haplotypes contain at least four nonoverlapping inversions that suppress recombination with the wild-type chromosome, and lock into strong linkage disequilibrium loci affecting normal transmission of the chromosome, male gametogenesis and embryonic development. Partial t-haplotypes derived through rare recombination between t-haplotypes and wild-type homologs have been critical in the analysis of these properties. Utilizing two new DNA probes. Au3 and Au9, and several previously described probes, we have analyzed the genetic structure of several partial t-haplotypes that have arisen in our laboratory, as well as several wild-type chromosomes deleted for loci in this region. With this approach we have been able to further our understanding of the structural and dynamic characteristics of the proximal region of the t-complex. Specifically, we have localized the D17Tul locus as most proximal known in t-haplotypes, achieved a better structural analysis of the partial t-haplotype t6, and defined the structure and lethal gene content of partial t-haplotypes derived from the lethal tw73 haplotype.

Animals↗
PubMed1989

Inducible responses to DNA damaging or stress inducing agents in Neurospora crassa.

Two-dimensional polyacrylamide gel electrophoresis has been used to analyze proteins from wild type and mutagen sensitive mutants of Neurospora crassa under constitutive conditions and after treatment with mutagens and other stress inducing agents. Several proteins have been detected that are either induced or show changes in electrophoretic mobility in response to UV irradiation, 4-NQO, X-ray, paraquat and heat shock. Ten proteins were found to respond to more than one of the stress inducing agents, demonstrating a complex pattern of polypeptide inductions. The significance of these findings and the possible effects of some of these proteins on the DNA repair process and stress management are discussed.

4-Nitroquinoline-1-oxide↗
PubMed1989

Intra-arterial digital subtraction angiography in the evaluation of peripheral vascular trauma.

The role of intra-arterial digital subtraction angiography (IADSA) in the evaluation of extremity trauma has not been clearly established. Several potential advantages would make IADSA a preferable study to conventional angiography (CA). This retrospective study analyzed 104 major peripheral arteries with suspected injury. Multiplane IADSA studies were compared with conventional angiography of the same vessel in 97 patients. The arteriograms were evaluated by a physician and a radiologist in a double-blinded fashion. IADSA correlated well with CA. Similar findings comparing both studies were noted in 101 of 104 angiograms (97%) (p less than 0.001) in review by the radiologist and in 100 of 104 (96%) (p less than 0.001) by the surgeon. Only one injury confirmed at surgery was not seen on IADSA; this study was read as equivocal by both examiners. These data confirm that IADSA is a reliable and reasonable study for the evaluation of patients with suspected peripheral arterial injury.

Angiography↗
PubMed1988

Relationship of histidine sensitivity to DNA damage and stress induced responses in mutagen sensitive mutants of Neurospora crassa.

Previous work in other laboratories has shown that several mutagen sensitive mutants of Neurospora crassa are extremely sensitive to low levels of histidine in the culture medium. We have shown that wild type Neurospora accumulates nicks or breaks in the DNA in the presence of histidine. The number of nicks accumulating in histidine sensitive mutants is found to increase in relation to their sensitivity to histidine. Although these nicks can be repaired by both wild type and histidine sensitive mutants when histidine is removed from the medium, a steady state number of nicks exists as long as histidine is present. We suggest that the presence of these nicks or breaks induces an increase in recombination in these possibly recombination defective mutants and that this is the source of the high level of histidine sensitivity. We speculate on the mechanisms by which histidine induces this DNA damage. This report also shows that several polypeptides are induced by the wild type organism in the presence of histidine. Some of these polypeptides are also induced during other stress situations, such as heat shock and DNA damage due to ultraviolet irradiation. Two of the histidine induced proteins cannot be induced by any of the histidine sensitive mutants.

DNA Damage↗
PubMed1988

Diabetes, gallbladder disease, obesity, and hypertension among Hispanics in New Mexico.

Because Hispanics in the Southwest are genetically admixed with American Indians, the hypothesis has been advanced that the excess occurrence of diabetes mellitus, obesity, and gallbladder disease in this ethnic group may be genetic in origin and results from genes derived from American Indians. This report describes the prevalence of these diseases in 1,175 adult Hispanic participants in a survey of a New Mexico community conducted in 1984-1985. At nearly all ages, the majority of subjects had a body mass index of 25 kg/m2 or greater, and a substantial proportion exceeded 30 kg/m2. The prevalence of obesity was much greater in these Hispanics than is shown in nationwide data for US whites. Diabetes mellitus was also reported more often by Hispanic subjects in this survey than by US whites nationwide. A report of gallbladder trouble or of gallbladder removal was common in both males and females; the prevalence of gallbladder removal was as high in this population as in Mexican Americans previously studied in Starr County, Texas. In spite of the high prevalence of obesity, hypertension was less frequent among the New Mexico Hispanics than is shown in nationwide data for US whites. These findings complement those of previous surveys in Texas, which have shown a notably high proportion of adults to be obese, to have non-insulin-dependent diabetes mellitus, and to have gallbladder disease. The similar epidemiology of these diseases in the Hispanics of New Mexico and the Mexican Americans of Texas supports the hypothesis that American Indian admixture underlies the development of these conditions in Hispanics throughout the Southwest.

Adolescent↗
PubMed1988

Discrepancies between self-reported and validated cigarette smoking in a community survey of New Mexico Hispanics.

In a population-based survey of respiratory disease in New Mexico Hispanics, we validated self-reports of cigarette use by 1,317 subjects against salivary cotinine level and end-tidal carbon monoxide concentration. For identifying likely deceivers about cigarette smoking among self-reported never smokers and former smokers, we used cutoff values of 20 ng/ml and 8 parts per million (ppm) for salivary cotinine and carbon monoxide, respectively. Among males and females, age-standardized prevalences of current smokers based upon questionnaire reports were 30.9 and 27.1%, respectively. After adjustment for cotinine alone, these percentages were 36.2 for males and 31.1 for females, and after adjustment for cotinine and carbon monoxide level, the corresponding percentages were 39.1 for males and 33.2 for females. We conclude that self-reports about smoking habits may lead to underestimation of the prevalence of current smokers and that questionnaire responses should be validated with biologic markers of tobacco smoke exposure.

Adolescent↗
PubMed1988

Respiratory diseases and cigarette smoking in a Hispanic population in New Mexico.

We have conducted a cross-sectional study of Hispanic residents of a community in New Mexico. A total of 2,111 subjects were recruited from 733 households; the overall participation rates were 68.1% for males and 78.9% for females. For all subjects, a standardized respiratory symptoms questionnaire was completed, spirometric testing was performed, and saliva and end-tidal breath samples were obtained. As in other populations, chronic respiratory symptoms were uncommon in children, and asthma was more prevalent in boys than in girls. In adults, physician-diagnosed chronic bronchitis and emphysema were less prevalent in this population than in a previously studied sample of non-Hispanic whites in New Mexico. Spirometric testing was confirmatory; less than 1% of the Hispanic males and females had chronic air-flow obstruction. The prevalence of cigarette usage in the Hispanics was comparable to data from non-Hispanic whites in New Mexico and from nationwide surveys. However, daily cigarette consumption by the Hispanics in this sample tended to be low, as found in previous studies in New Mexico and elsewhere.

Adolescent↗