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Biomedical subjects

A J White

Publications and source records attributed to A J White.

At least 37 records · Page 2Linked to original sources

Poly(ADP-ribosyl)ation basally activated by DNA strand breaks reflects glutamate-nitric oxide neurotransmission.

Poly(ADP-ribose) polymerase (PARP) transfers ADP ribose groups from NAD(+) to nuclear proteins after activation by DNA strand breaks. PARP overactivation by massive DNA damage causes cell death via NAD(+) and ATP depletion. Heretofore, PARP has been thought to be inactive under basal physiologic conditions. We now report high basal levels of PARP activity and DNA strand breaks in discrete neuronal populations of the brain, in ventricular ependymal and subependymal cells and in peripheral tissues. In some peripheral tissues, such as skeletal muscle, spleen, heart, and kidney, PARP activity is reduced only partially in mice with PARP-1 gene deletion (PARP-1(-/-)), implicating activity of alternative forms of PARP. Glutamate neurotransmission involving N-methyl-d-aspartate (NMDA) receptors and neuronal nitric oxide synthase (nNOS) activity in part mediates neuronal DNA strand breaks and PARP activity, which are diminished by NMDA antagonists and NOS inhibitors and also diminished in mice with targeted deletion of nNOS gene (nNOS(-/-)). An increase in NAD(+) levels after treatment with NMDA antagonists or NOS inhibitors, as well as in nNOS(-/-) mice, indicates that basal glutamate-PARP activity regulates neuronal energy dynamics.

Animals↗

Workforce projections for optometry.

BACKGROUND: A 1995 workforce study conducted by RAND estimated a large current surplus of eye care providers in the United States. Due to data limitations of the RAND study and the outdated optometric workforce information available, the American Optometric Association contracted with Abt Associates to conduct a study to project future workforce requirements for optometry. METHODS: We collected extensive data on both the supply (work hours, retirement rates, new entrants) and demand (patient encounters and associated time requirements) of optometrists. These data were collected from a survey using stratified random sampling of 1,100 practicing optometrists and were used to develop workforce projections for optometry through the year 2030. Projections were calculated using a forecasting tool that can be used to derive workforce and training requirements under a range of future scenarios. RESULTS: Workforce projections suggest an excess supply of optometrists is likely over the next 20 years. Over the next five years, approximately 550 optometrists are expected to retire each year, while more than 1,100 optometrists enter practice annually. Patient encounter volume is projected to increase steadily, but the effects of this increase are largely offset by an anticipated decrease in optometrist time requirements for routine eye examinations. DISCUSSION: To reduce the size of the anticipated excess supply, optometry may want to focus on ways that demand can be increased. One way to increase demand is through greater convergence between the actual demand for eye care services and the underlying public health need for eye care.

Adult↗

A simple method for measuring severely reduced glomerular filtration rate.

OBJECTIVE: The purpose of this study was to develop a simpler method to measure severely reduced glomerular filtration rate (GFR) for patients with a GFR below 30 mL/min. METHOD: The GFR was measured in 24 patients using both the 51Cr EDTA slope-intercept method (the conventional method) and 99mTc-DTPA with our proposed simpler GFRn method. RESULTS: The correlation coefficient was 0.92 between the 2 methods, with a slope of 0.97 and an intercept of 2 mL/min. CONCLUSION: Our simplified method for measuring GFR is accurate for most patients with severely reduced GFR. Errors are acceptably small in patients with severely reduced GFR when edema or dehydration are present. If extrarenal (liver) clearance is significant, however, a urine sampling method is required for an accurate GFR measurement.

Algorithms↗

Temporal contrast sensitivity in the lateral geniculate nucleus of a New World monkey, the marmoset Callithrix jacchus.

1. The temporal contrast sensitivity of koniocellular, parvocellular and magnocellular cells in the lateral geniculate nucleus (LGN) of nine adult marmosets was measured. The receptive fields of the cells were between 0.3 and 70 deg from the fovea. The stimulus was a large spatially uniform field which was modulated in luminance at temporal frequencies between 0.98 and 64 Hz. 2. For each cell group there was a gradual increase in modulation sensitivity, especially for temporal frequencies below 8 Hz, with increasing distance from the fovea. At any given eccentricity, magnocellular cells had the greatest sensitivity. In central visual field, the sensitivity of koniocellular cells lay between that of parvocellular and magnocellular cells. In peripheral visual field (above 10 deg eccentricity) koniocellular and parvocellular cells had similar sensitivity. 3. The contrast sensitivity of each cell class was dependent on the anaesthetic used. Cells from animals anaesthetized with isoflurane were less sensitive than cells from animals anaesthetized with sufentanil. This effect was more marked for temporal frequencies below 4 Hz. 4. These results are incompatible with the notion that the koniocellular pathway is functionally homologous to a sluggish, W-like pathway in other mammals. At least in terms of their temporal transfer properties, many koniocellular cells are more like parvocellular cells.

Animals↗

Re-evaluation of the primary structure of Ralstonia eutropha phasin and implications for polyhydroxyalkanoic acid granule binding.

Sequence analysis of several cDNAs encoding the phasin protein of Ralstonia eutropha indicated that the carboxyl terminus of the resulting derived protein sequence is different from that reported previously. This was confirmed by: (1) sequencing of the genomic DNA; (2) SDS-PAGE and peptide analysis of wild-type and recombinant phasin; and (3) mass spectrometry of wild-type phasin protein. The results have implications for the model proposed for the binding of this protein to polyhydroxyalkanoic acid granules in the bacterium.

Alcaligenes↗

A report on home visiting practices conducted in remote districts of Nepal in an NGO-run tuberculosis control programme.

To establish the role of home visiting in an NGO-run tuberculosis control programme in Nepal, information was collected on home visits to a cohort of 205 smear-positive patients. Almost one third of new smear-positive cases were visited, either for treatment initiation (n = 33) or for retrieval following non-attendance (n = 29); thus 14% of patients required a home visit to ensure treatment completion. It is unlikely that the WHO-recommended target of 85% cure rate would be achieved without defaulter tracing, although a further study comparing home visiting against no visiting would be necessary to assess the contribution that this activity makes to improving treatment outcomes.

Antitubercular Agents↗

Identification of promoter elements in a low-temperature-responsive gene (blt4.9) from barley (Hordeum vulgare L.).

The blt4 barley gene family encodes non-specific lipid transfer proteins and has been shown, by in situ localisation, to be expressed in the epidermal cells of leaves. The transcriptionally controlled, low-temperature-responsive member of this gene family, blt4.9, is predominantly expressed in shoot meristems. The promoter region (1938 bp) of blt4.9 contains sequence motifs which have been implicated in responses to low temperature, abscisic acid and other environmental factors. Deletion analysis showed that a 42 bp sequence proximal to, but not including, the CAAT and TATA boxes, confers enhanced low-temperature response to a reporter gene in a barley shoot explant transient expression system. Other promoter regions were shown to contain negative and positive regulatory regions. Electrophoretic mobility shift analysis (EMSA) was used with nuclear proteins from either low-temperature- or control-temperature-treated plants to further investigate the blt4.9 promoter. Synthetic oligonucleotides were used to identify a hexanucleotide, CCGAAA, within the 42 bp, low-temperature-responsive promoter region, as the binding site of a low-mobility nuclear protein complex. This complex was present in nuclear extracts from both low-temperature-treated and control plants and was the only complex formed within this region. Mutation of the CCGAAA motif within the low-temperature-responsive 42 bp promoter sequence reduced low-temperature responsiveness to basal levels. A related upstream element, CCGAC, known to be a low-temperature-responsive element in other plants, did not bind to nuclear proteins in this study. It is proposed that the hexanucleotide CCGAAA, at -195 from the first ATG, is involved in the low-temperature response of blt4.9 in barley.

Base Sequence↗

What if socioeconomics made no difference?: access to a cadaver kidney transplant as an example.

OBJECTIVES: Several studies have noted the impact of socioeconomic factors on access to expensive medical care, but none of those studies controlled for self-reported health and functional status or attitudes about treatment alternatives when analyses were completed. Because these factors may be correlated with socioeconomic status, the failure to control for them may have led to bias in other studies. The authors merged data from secondary sources with telephone survey data from a national sample of 456 end-stage renal disease patients to show how estimates of the effects of socioeconomic factors change when self-reported health and functional status and attitudes about treatment are incorporated into statistical models. The authors also showed how kidney transplant rates would change if socioeconomic factors no longer influences organ allocation decisions. METHODS: Weibull proportional hazard analyses were used to show relationships between socioeconomic measures and waiting list entry and kidney transplant rates, before versus after accounting for self-reported health and functional status, attitudes about treatment, and other variables. Simulation analyses were used to estimate the number of waiting list spots and transplant operations that would move from economically advantaged to disadvantaged persons if socioeconomics no longer influenced organ allocation decisions. RESULTS: Incorporating information about health and functional status, attitudes about treatment, and other factors into the hazard models often reduced the estimated impact of socioeconomic measures on the odds of (1) being on a waiting list for a cadaver kidney transplant and (2) receiving a transplant. Simulations showed that 30 to 65 waiting list spots or transplant operations per 1,000 patients would shift from economically advantaged to disadvantaged persons if socioeconomics no longer influenced organ allocation decisions. CONCLUSIONS: Successful efforts to level the playing field would result in substantial redistributions of kidney transplants from economically advantaged to disadvantaged persons.

Adolescent↗

Segregation of receptive field properties in the lateral geniculate nucleus of a New-World monkey, the marmoset Callithrix jacchus.

The lateral geniculate nucleus (LGN) in humans and Old-World monkeys is dominated by the representation of the fovea in the parvocellular (PC) layers, and most PC cells in the foveal representation have red-green cone opponent receptive field properties. It is not known whether these features are both unique to trichromatic primates. Here we measured receptive field properties and the visuotopic organization of cells in the LGN of a New-World monkey, the marmoset Callithrix jacchus. The marmoset displays a polymorphism of cone opsins in the medium-long wavelength (ML) range, which allows the LGN of dichromatic ("red-green color blind") and trichromatic individuals to be compared. Furthermore, the koniocellular-interlaminar layers are segregated from the main PC layers in marmoset, allowing the functional role of this subdivision of the LGN to be assessed. We show that the representation of the visual field in the LGN is quantitatively similar in dichromatic and trichromatic marmosets and is similar to that reported for macaque; the vast majority of LGN volume is devoted to the central visual field. ON- and OFF-type responses are partially segregated in the PC layers so that responses are more commonly encountered near the external border of each layer. The red-green (ML) opponent cells in trichromatic animals were all located in the PC layers, and their receptive fields were within 16 degrees of the fovea. The koniocellular zone between the PC and magnocellular layers contained cells that receive excitatory input from short wavelength sensitive cones ("blue- cells") as well as other nonopponent cells. These results suggest that the basic organization of the LGN is common to dichromatic and trichromatic primates and provide further evidence that ML and SWS opponent signals are carried in distinct subdivisions of the retinogeniculocortical pathway.

Animals↗

The effects of New York state's ban on multiple listing for cadaveric kidney transplantation.

OBJECTIVE: To study the effectiveness of a 1990 ban by New York state on entry to more than one waiting list for a cadaver kidney transplant, and the impact of the ban on equity in access to transplantation. DATA SOURCES: (1) Waiting list files from the Organ Procurement and Transplantation Network, (2) the Health Care Financing Administration's Medicare Program Management and Medical Information System, and (3) U.S. Census Public Use Files. STUDY DESIGN: Multivariate hazard models were used to estimate the impact of the ban of the overall odds of multiple listing and on the odds of multiple listing at in-state and out-of-state transplant centers. After estimating the relationship between multiple listing and subsequent transplantation, we used simulation techniques to estimate the effects of a complete multiple listing ban on group waiting time differentials. Independent variables included demographic/socioeconomic characteristics, measures of ESRD severity, general transplantation suitability, measures that affect the likelihood of finding a good donor organ, and measures of the productivity of the transplant/dialysis center. PRINCIPAL FINDINGS: The ban was associated with a 66 percent reduction in the rate of multiple listing for New York patients, and multiple listing at in-state transplant centers declined by 87 percent. Simulation results suggested that even a completely effective ban would produce only small, mixed equity effects. CONCLUSIONS: While the ban was effective in reducing the proportion of patients who registered at multiple transplant centers, taken together the results suggest that banning multiple listing is not likely to result in large improvements in equity in access to transplantation.

Adolescent↗

The inhibition of vascular smooth muscle cell migration by peptide and antibody antagonists of the alphavbeta3 integrin complex is reversed by activated calcium/calmodulin- dependent protein kinase II.

The migration of vascular smooth muscle cells (VSMCs) is thought to play a key role in the pathogenesis of many vascular diseases and is regulated by soluble growth factors/ chemoattractants as well as interactions with the extracellular matrix. We have studied the effects of antibodies to rat beta3 and human alphavbeta3 integrins on the migration of VSMCs. Both integrin antibodies as well as cyclic RGD peptides that bind to the vitronectin receptors alphavbeta3 and alphavbeta5 significantly inhibited PDGF-directed migration. This resulted in a reduction in the accumulation of inositol (1,4,5) trisphosphate and the activation of calcium/calmodulin-dependent protein kinase II (CamKII), an important regulatory event in VSMC migration identified previously. PDGF-directed VSMC migration in the presence of the anti-integrin antibodies and cyclic RGD peptides was restored when intracellular CamKII activity was elevated by either raising intracellular calcium levels with the ionophore, ionomycin, or infecting with a replication-defective recombinant adenovirus expressing a constitutively activated CamKII cDNA (AdCMV.CKIID3). Rescue of rat VSMCs was also observed in stably transfected cell lines expressing constitutively activated but not wild-type CamKII. These observations identify a key intermediate in the regulation of VSMC migration by outside-in signaling from the integrin alphavbeta3.

Animals↗

Minimizing racial disparity regarding receipt of a cadaver kidney transplant.

This report describes the impact of race on waiting list entry and receipt of a cadaver kidney transplant, after accounting for self-reported income, health and functional status, and patients' attitudes about dialysis and transplantation as treatment alternatives. Previous studies did not account for these race-related factors and therefore produced biased estimates of the impact of race on waiting list entry and receipt of a transplant. Data for this investigation came from a telephone survey of a national sample of 456 end-stage renal disease patients and from files maintained by the United Network for Organ Sharing and the Health Care Financing Administration. Proportional hazard models were estimated with these data. The results indicated that approximately 60% of the differences between black and white waiting list entry rates and 52% of the black-white differences in transplantation rates were due to race-related differences in socioeconomic status, health and functional status, severity of illness, biological factors, the existence of contraindications to transplantation, transplant center characteristics, and patients' attitudes about dialysis and transplantation. Potential ways to narrow racial differences further include better education about treatment alternatives for black patients, more vigorous efforts to obtain donor organs from minorities, continued research and thoughtful policy on the access-related impacts of United Network for Organ Sharing point system variances, and consolidation of some smaller waiting lists into larger regional lists.

Adolescent↗

Evidence that blue-on cells are part of the third geniculocortical pathway in primates.

Colour vision in primates is mediated by cone opponent ganglion cells in the retina, whose axons project to the dorsal lateral geniculate nucleus in the visual thalamus. It has long been assumed that cone opponent ganglion cells project to the parvocellular layers of the geniculate. Here, we examine the role of a third subdivision of the geniculocortical pathway: the interlaminar or koniocellular geniculate relay cells. We made extracellular recordings in the dorsal lateral geniculate nucleus of the common marmoset Callithrix jacchus, a New World monkey in which the interlaminar cells are well segregated from the parvocellular layers. We found that one group of colour opponent cells, the blue-on cells, was largely segregated to the interlaminar zone. This segregation was common to dichromatic ('red-green colour-blind') and trichromatic marmosets. The result calls into question the traditional notion that all colour information passes through the parvocellular division of the retino-geniculo-cortical pathway in primates.

Animals↗

General health of end stage renal disease program beneficiaries.

A telephone survey of a national sample of 515 Medicare End Stage Renal Disease Program beneficiaries was conducted to obtain information on their health status and its determinants. The Medical Outcomes Study Short Form-36 (SF-36) was applied during the interview process to obtain the health-status information. The reliability of each SF-36 health-status dimension was at least 0.85, and the validity of seven of the eight dimensions was high. Weighted least-squares regression results showed that health-status levels were often lower among older patients and Hispanic persons, and sometimes lower for those with low incomes. The implications of using the SF-36 for health-status measurement are also described.

Activities of Daily Living↗

Biotin carboxyl carrier protein and carboxyltransferase subunits of the multi-subunit form of acetyl-CoA carboxylase from Brassica napus: cloning and analysis of expression during oilseed rape embryogenesis.

In the oilseed rape Brassica napus there are two forms of acetyl-CoA carboxylase (ACCase). As in other dicotyledonous plants there is a type I ACCase, the single polypeptide 220 kDa form, and a type II multi-subunit complex analogous to that of Escherichia coli and Anabaena. This paper describes the cloning and characterization of a plant biotin carboxyl carrier protein (BCCP) from the type II ACCase complex that shows 61% identity/79% similarity with Anabaena BCCP at the amino acid level. Six classes of nuclear encoded oilseed rape BCCP cDNA were clones, two of which contained the entire coding region. The BCCP sequences allowed the assignment of function to two previously unassigned Arabidopsis expressed sequence tag (EST) sequences. We also report the cloning of a second type II ACCase component from oilseed rape, the beta-carboxyltransferase subunit (betaCT), which is chloroplast-encoded. Northern analysis showed that although the relative levels of BCCP and betaCT mRNA differed between different oilseed rape tissues, their temporal patterns of expression were identical during embryo development. At the protein level, expression of BCCP during embryo development was studied by Western blotting, using affinity-purified anti-biotin polyclonal sera. With this technique a 35 kDa protein thought to be BCCP was shown to reside within the chloroplast. This analysis also permitted us to view the differential expression of several unidentified biotinylated proteins during embryogenesis.

Acetyl-CoA Carboxylase↗

Diagnosis and management of serious urinary complications after major operative laparoscopy.

OBJECTIVE: To evaluate the incidence, diagnosis, and management of serious urinary complications after major operative laparoscopy. METHODS: For this retrospective study of 953 consecutive cases of major operative laparoscopy from January 1, 1990, to December 31, 1994, we reviewed incidence, method of diagnosis, and management of complications. Urinary complications included bladder injuries, urinary fistulas, and ureteral injuries. Major operative laparoscopic procedures included hysterectomy, adnexectomy, treatment of tubal pregnancy, ovarian cystectomy, and ablation-fulguration of severe endometriosis (stage IV). RESULTS: Serious urinary complications were found during or after operative laparoscopy in 15 of 953 patients (1.6%, 95% confidence interval [CI] 0.8-2.4). Four ureteral injuries, three bladder fistulas, and eight bladder perforations were documented in this series. Eight cases of urinary complications were recognized during the original surgery (one ureteral injury and seven bladder injuries) and repaired at that time. Laparotomy or additional major surgery was performed in seven patients (three ureteral injuries, two bladder fistulas, and two bladder perforations). CONCLUSIONS: Serious urinary complications after major operative laparoscopy were discovered in 1.6% of patients. This incidence compares favorably to serious urinary complications after standard gynecologic surgery. Intraoperative recognition of these complications will likely avoid additional surgery.

Adolescent↗