Biomedical subjects
Publications and source records attributed to K Howard.
In many animals, germ cells migrate to the gonad to assemble into a functional organ. Recent work in Drosophila has built a picture of the gene activities that specify the gonad and allow it to attract germ cells, and has led to the identification of a gene, columbus, that may encode the attractive factor.
The accuracy of a dementia diagnosis by specialist physicians, as verified at an autopsy, is greater than 90% in many series. Donations of brains to the Maritime Brain Tissue Bank (MBTB) by individuals who did not have expert dementia diagnoses before death led us to investigate whether clinical features could also be detected retrospectively. Informants for 36 individuals whose brains were in the MBTB (18 women, mean age = 79 years; pathologic diagnoses: 75% Alzheimer's disease [AD]; 8.4% vascular or mixed dementia) were interviewed by specialist physicians using a semistructured retrospective interview based on the Brief Cognitive Rating Scale (BCRS) (range = 1 [no impairment] to 7 [terminal dementia]). The mean duration of dementia was 8.5 +/- 12.8 years based on proxy reports, and most cases suggested severe dementia--(stage 6 [severe] or 7 [terminal])--on the retrospective BCRS (RetroBCRS) before death. A score of 4 or more on the RetroBCRS had 100% sensitivity and specificity in detecting dementia. The RetroBCRS score correlated moderately with duration (.51). In linear and logistic regression models adjusted for age and sex, RetroBCRS staging helped explain 93% of the variation in duration. The accuracy of the retrospective diagnosis of the cause of dementia, compared with autopsy, was 92%. The RetroBCRS used by an expert physician with a reliable informant is a valid method of detecting dementia and determining whether AD was present.
OBJECTIVE: To determine whether the subclassification of indeterminate ultrasound readings can identify patients who are at high, intermediate, or low risk for ectopic pregnancy. METHODS: A retrospective review was made of consecutive ED patients presenting to an urban teaching hospital from August 1991 to December 1994 with abdominal pain and/or vaginal bleeding and a positive beta-hCG. Patients who had transvaginal ultrasonograms obtained during the ED visit that were read as indeterminate (no extrauterine findings of ectopic pregnancy and no intrauterine fetal pole or yolk sac) were eligible. Ultrasonograms were subclassified into 5 groups (empty uterus, nonspecific intrauterine fluid, echogenic debris within endometrial cavity, abnormal sac, normal sac) based on predetermined criteria. Patients were excluded if the final diagnosis could not be definitively determined. RESULTS: 248 patients were identified. 20 patients were excluded because a final diagnosis could not be determined. Patients with an empty uterus [25/94 = 27% (95% CI 18-36%)] had the highest frequency of ectopic pregnancy. Patients with nonspecific intrauterine fluid collections [4/30 = 13% (95% CI 4-31%)] had the next highest frequency of ectopic pregnancy. Patients with intrauterine echogenic debris [2/39 = 5% (95% CI 1-11%)], abnormal sacs [1/36 = 3% (95% CI 1-9%)], or normal-appearing sacs [0/29 = 0% (95% CI 0-8%)] had low frequencies of ectopic pregnancy. CONCLUSION: Subclassification of indeterminate ultrasound readings identifies patients at high, intermediate, or low risk for ectopic pregnancy and should improve the diagnostic accuracy of ultrasonography in patients at risk for ectopic pregnancy.
We have previously reported a linkage between radiation-induced damage to a putative tumor suppressor locus on fibroblast chromosome 11 and the re-expression of tumorigenicity in a hybrid cell line (HeLa x human skin fibroblast) used to study neoplastic transformation. Further investigation into the molecular basis of radiation-induced neoplastic transformation of the hybrid cell, CGL1, indicates that loss of fibroblast chromosome 11 appears to be necessary but not sufficient for neoplastic transformation. Previous analysis had suggested, though not clearly demonstrated, a possible role for loss of alleles on fibroblast chromosome 14 in the neoplastic transformation of the hybrid cells. Therefore, the status of chromosome 14 in the gamma-ray-induced, neoplastically transformed (GIM) hybrid cell lines and in nontumorigenic control (CON) hybrid cell lines isolated from irradiated populations has been investigated. Chromosome painting and molecular studies using restriction fragment length polymorphisms and tetranucleotide repeat polymorphism analysis were performed. As an additional control, the status of chromosome 12 was also examined. We report that five of the eight GIM cell lines have lost one complete copy of a fibroblast chromosome 14 while only one of the five CON cell lines has lost a complete copy of a fibroblast chromosome 14. No evidence of large-scale loss of chromosome 12 was detected in the GIM or CON cells. The data further suggest that both copies of fibroblast chromosome 14 contain an active tumor suppressor locus and that radiation-induced loss of either fibroblast chromosome 14 is associated with neoplastic transformation in this system. We now conclude that loss of alleles on both fibroblast chromosome 11 and 14 may be required for the radiation-induced neoplastic transformation of these human hybrid cells.
In Drosophila, germ cells migrate in embryonic development from the lumen of the developing gut towards the overlying mesoderm, where they enter the gonads. The gene wunen is responsible for guiding the germ cells early in this process. Here we report that the protein Wunen has two properties that allow it to use repulsion to guide the germ cells. Wunen can transform a permissive cellular environment into a repulsive one, and is expressed in the gut in a pattern that guides germ cells towards the mesoderm. Wunen shows strong similarity to the enzyme type 2 phosphatidic acid phophatase (PAP2)4, suggesting that it is involved in lipid metabolism.
Previous studies by these investigators have shown that mannosylated bovine serum albumin (m-BSA) enhances the respiratory burst (RB), phagocytosis, and killing of Candida albicans by resident murine peritoneal macrophages (MO). Upregulation of the above MO functions was associated with binding of m-BSA to the MO-mannose receptor. The present study was done to determine if the immunostimulant, acemannan prepared from aloe vera, could stimulate MO in a similar manner. Resident peritoneal MO collected from C57BL/6 mice were exposed to acemannan for 10 min. The RB was measured using chemiluminescence and demonstrated approximately a two-fold increase above the media controls. In studies involving phagocytosis, MO were exposed to acemannan, washed and exposed to Candida at a ratio of 1:5. The percent phagocytosis and Candida killing were determined using fluorescence microscopy. There was a marked increase in phagocytosis in the treated cultures (45%) compared to controls (25%). Macrophages exposed to acemannan for 10 min resulted in ca 38% killing of Candida albicans compared with 0-5% killing in controls. If MO were incubated with acemannan for 60 min, 98% of the yeast were killed compared to 0-5% in the controls. The results of the present study indicate that short term exposure of MO to acemannan upregulates the RB, phagocytosis and candidicidal activity. Further studies are needed to clarify the potential use of this immunostimulant as an anti-fungal agent.
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We describe a novel genetic locus, wunen (wun), required for guidance of germ cell migration in early Drosophila development. Loss of wun function does not abolish movement but disrupts the orientation of the motion causing the germ cells to disperse even though their normal target, the somatic gonad, is well formed. We demonstrate that the product of this gene enables a signal to pass from the soma to the germ line and propose that the function of this signal is to selectively stabilize certain cytoplasmic extensions resulting in oriented movement. To characterize this guidance factor, we have mapped wun to within 100 kb of cloned DNA.
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A simple, small scale non-hazardous procedure for the production of magnetizable solid-phase support (MSPS) beads has been developed based on the extrusion of agarose/iron oxide mixtures. The MSPS beads were derivatized using various amine ligands. Derivatized MSPS beads were used to adsorb nucleic acids from aqueous solution and to separate RNA/DNA mixtures.
We report data on the validity and responsiveness (i.e. sensitivity to change) of assessment instruments including Goal Attainment Scaling (GAS), at a single site in a multicentre trial of the experimental therapeutic agent linopirdine. Fifteen people (11 women) were evaluated. GAS yielded a mean 3.7 goals per patient (range 2-6). The mean gain in the GAS scores, 2.7 +/- 16.4, was compared to changes in the Alzheimer's Disease Assessment Scale-Cognitive Section, the Global Deterioration Scale, Clinical Global Impression and the Mini-Mental State Exam. GAS had the largest relative efficiency (0.47) when compared to the standard. GAS also had the largest effect size (0.61). The data suggest that an individualized approach may have merit as an outcome measure and as a means to better understanding treatment effects. Qualitative analysis revealed consistent goal setting in self-care, behaviour, cognition and leisure, suggesting that these areas should routinely be evaluated.
To gain insight into the role of the insulin-like growth factors (IGFs) in regulating lung development, we have used in situ hybridization histochemistry (ISHH) to examine the ontogeny and sites of expression of IGF-I and IGF-II, IGF binding proteins (IGFBP-1 to IGFBP-6), and IGF cell surface receptors in fetal rat lung from 15 to 21 days of gestation. Both IGF-I and IGF-II mRNAs were expressed throughout the developmental period studied with little change in apparent abundance. IGF-I mRNA localized to mesenchymal cells, especially those surrounding airway epithelium, while IGF-II mRNA, which was somewhat more abundant, localized predominantly to epithelia. The type 1 IGF receptor, the receptor that likely mediates the actions of both IGFs, was expressed widely in virtually all cells, whereas the expression of the type 2 IGF receptor, thought to be involved in IGF internalization and degradation, was confined to the mesenchyme and medial layers of intrapulmonary vessels. As with the IGFs, there was little apparent change in the abundance of IGF receptor mRNAs through fetal development, and the type 2 IGF receptor mRNA was more abundant. The expression of IGFBPs changed significantly during lung development. IGFBP-2, -3, -4, and -5 were expressed from day 15 of gestation, but their sites of expression and ontogeny differed. IGFBP-2 mRNA expression was abundant and constant throughout gestation and was confined to proximal and distal airway epithelia. IGFBP-3 and IGFBP-5 also were expressed by proximal airway epithelia, but also exhibited significant expression in interstitial mesenchyme and in mesenchyme surrounding vessels. The abundance of both increased as gestation progressed (IGFBP-5 greater than IGFBP-3). IGFBP-4 mRNA was confined to interstitial mesenchyme and its abundance peaked at days 16 to 19 of gestation. We found no evidence for expression of either IGFBP-1 or IGFBP-6. We conclude that the expression of IGF-I, IGF-II, and the type 1 IGF receptor throughout gestation in the lung supports a role for the IGFs in lung growth and development. The complex pattern of IGFBP expression (differing sites and ontogeny of expression) suggests that the IGFBPs modulate IGF actions at specific target sites. Furthermore, because there is little change in the expression of IGFs or IGF receptor mRNAs during fetal lung development, regulation of IGFBP expression may be essential to the control of IGF actions during lung development.
Students participating in this clinical exercise learned to critically evaluate problems occurring in their practice areas. In addition, they learned ways of addressing problems through nursing diagnosis. They experienced research as they conducted surveys, calculated results, and listed characteristics. The students had the opportunity to create a product. Unfortunately, as students graduated and became busy with their new positions, they no longer pursued the academic activity of getting a diagnosis accepted by NANDA. The acceptance process seemed particularly formidable after the initial rejection. An even more serious loss exists for graduates who work in gerontological nursing--that of not having these existent problems readily identified and labeled.
To examine the relationship between the plasma glucose concentration (PG) and the pathways of hepatic glucose production (HGP), five groups of conscious rats were studied after a 6-h fast: (a) control rats (PG = 8.0 +/- 0.2 mM); (b) control rats (PG = 7.9 +/- 0.2 mM) with somatostatin and insulin replaced at the basal level; (c) control rats (PG = 18.1 +/- 0.2 mM) with somatostatin, insulin replaced at the basal level, and glucose infused to acutely raise plasma glucose by 10 mM; (d) control rats (PG = 18.0 +/- 0.2 mM) with somatostatin and glucose infusions to acutely reproduce the metabolic conditions of diabetic rats, i.e., hyperglycemia and moderate hypoinsulinemia; (e) diabetic rats (PG = 18.4 +/- 2.3 mM). All rats received an infusion of [3-3H]glucose and [U-14C]lactate. The ratio between hepatic [14C]UDP-glucose sp act (SA) and 2X [14C]-phosphoenolpyruvate (PEP) SA (the former reflecting glucose-6-phosphate SA) measured the portion of total glucose output derived from PEP-gluconeogenesis. In control rats, HGP was decreased by 58% in hyperglycemic compared to euglycemic conditions (4.5 +/- 0.3 vs. 10.6 +/- 0.2 mg/kg.min; P < 0.01). When evaluated under identical glycemic conditions, HGP was significantly increased in diabetic rats (18.9 +/- 1.4 vs. 6.2 +/- 0.4 mg/kg.min; P < 0.01). In control rats, hyperglycemia increased glucose cycling (by 2.5-fold) and the contribution of gluconeogenesis to HGP (91% vs. 45%), while decreasing that of glycogenolysis (9% vs. 55%). Under identical plasma glucose and insulin concentrations, glucose cycling in diabetic rats was decreased (by 21%) and the percent contribution of gluconeogenesis to HGP (73%) was similar to that of controls (84%). These data indicate that: (a) hyperglycemia causes a marked inhibition of HGP mainly through the suppression of glycogenolysis and the increase in glucokinase flux, with no apparent changes in the fluxes through gluconeogenesis and glucose-6-phosphatase; under similar hyperglycemic hypoinsulinemic conditions: (b) HGP is markedly increased in diabetic rats; however, (c) the contribution of glycogenolysis and gluconeogenesis to HGP is similar to control animals.
Cell migration is a common feature of development. In order to understand more about the factors that control these movements we have embarked on further analysis of the migration of Drosophila germ cells. This process involves passage of the germ cells across the gut primordium and migration toward the mesoderm where the somatic gonad forms. We are particularly interested in the early phase of this migration when the germ cells interact with the amnioproctodeal invagination, the developing gut, before entering into association with the mesoderm. We will summarize the results of our and other studies of these events before describing a number of enhancer trap lines which show expression in the amnioproctodeal invagination during the early phase of germ cell migration. These reveal more about the complexity of this tissue and suggest this tissue is capable of guiding the early phase of germ cell migration.
452 male technical and vocational students aged 16-25 years old were surveyed for their dietary habits at Riyadh, Saudi Arabia. The data presented here cover the habit of meal skipping. Results showed that dinner was skipped by 28%, breakfast by 20% and lunch was skipped by 15%. Differences are discussed according to age cohorts and accommodation status subgroups.
Dietary habits of 452 young adult male students at 6 technical institutes and vocational training centres in Riyadh, Saudi Arabia were investigated as part of a nutritional assessment survey. The eating-between-meals habit was found to be common among the majority (72.3%) of those students. The association between this habit and age cohorts, marital status, accommodation status, self assessment of weight and exercising are discussed.