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Biomedical subjects

C L White

Publications and source records attributed to C L White.

At least 55 records · Page 3Linked to original sources
PubMed1997

Role of glucose, fatty acids and protein in regulation of testicular growth and secretion of gonadotrophin, prolactin, somatotrophin and insulin in the mature ram.

This study tested whether the effects of nutrition on gonadotrophin secretion and testicular growth in mature rams are due to increases in the supply of glucose, fatty acids (FA) or amino acids. Responses to protein (casein) and glucose, alone or in combination, were compared with responses to lupin grain and responses to a combination of protein, glucose and FA (acetate, propionate and vegetable oil). Glucose and casein were infused intra-abomasally whereas lupins and FA were added to the diet. Lupin feeding decreased blood growth hormone (GH) concentrations, but increased pulsatile luteinizing hormone (LH) secretion and increased the concentrations of follicle-stimulating hormone (FSH), prolactin, glucose and insulin. These effects were associated with testicular growth. Glucose or casein increased insulin concentrations and decreased GH concentrations, but did not affect gonadotrophins or testicular growth. There was no synergism between casein and glucose. Responses elicited by adding FA to the glucose+casein treatment were similar to those observed with lupins. In conclusion, the reproductive axis does not seem to be closely linked with dietary intakes of amino acids or with circulating concentrations of glucose, insulin or GH. However, the energetic components of the diet, particularly the fatty acids, appear to play a key role in the reproductive responses to changes in nutrition.

Analysis of Variance↗
PubMed1997

Interphase cytogenetic (in situ hybridization) analysis of astrocytomas using archival, formalin-fixed, paraffin-embedded tissue and nonfluorescent light microscopy.

Astrocytomas contain nonrandom chromosomal abnormalities that recently have been correlated with shortened patient survival. Two frequently reported aberrations are trisomy 7 and monosomy 10. We assessed the numerical complement of chromosomes 7 and 10 in formalin-fixed, paraffin-embedded brain biopsy tissue from 28 diffuse astrocytomas by in situ hybridization using a nonfluorescent enzymatic detection system. Clinical follow-up of at least 5 years was available in 26 cases (93%). Monosomy 10 was identified in 7 cases (25%): astrocytoma, 1 case; anaplastic astrocytoma, 1 case; and glioblastoma, 5 cases. Trisomy 7 was identified in 11 cases (39%): astrocytoma, 5 cases; glioblastoma, 6 cases. Multivariate analysis revealed that monosomy 10 was the most statistically significant negative predictor of patient survival. Numerical chromosomal abnormalities are detectable in astrocytomas in archival tissue using interphase cytogenetics and nonfluorescent light microscopy. Although larger studies are required, our data suggest that potentially useful prognostic information may be obtained with this approach.

Adult↗
PubMed1997

Frequency of unilateral and bilateral mesial temporal sclerosis in primary and secondary epilepsy: a forensic autopsy study.

Controversy exists regarding the pathogenetic relationship of mesial temporal sclerosis (MTS) to epileptogenesis. Some investigators view hippocampal sclerosis as the primary cause of temporal lobe epilepsy, whereas others interpret the changes to be the result of chronic seizure activity. The present autopsy-based study attempts to clarify the etiologic relationship between mesial temporal sclerosis and epilepsy. To investigate the assumption that bilateral MTS is more likely to be the result of chronic seizure activity associated with a seizure focus outside the hippocampus, two subject groups were identified. The first group comprised 43 patients who had no extrahippocampal pathology and were classified as having primary epilepsy. The second group comprised 35 patients who, had identifiable extrahippocampal pathology and were classified as having secondary epilepsy. Fifteen of the 35 cases of secondary epilepsy also had MTS; seven of these were unilateral and eight were bilateral. Of the 43 cases with primary epilepsy, only one had MTS, and it was unilateral. Significantly more cases of primary epilepsy than secondary epilepsy had no MTS (p < 0.001), suggesting that both unilateral and bilateral forms of MTS occur with greater frequency in subjects with seizure foci outside the hippocampus. These results also suggest that unilaterality of MTS does not exclude an extrahippocampal cause.

Adolescent↗
PubMed1997

Expression of telomerase RNA component correlates with the MIB-1 proliferation index in ependymomas.

Although there is general agreement that certain morphologic subtypes of ependymoma are benign, the biologic behavior of other ependymal neoplasms is poorly understood and not clearly related to conventional histopathologic criteria. The absence of universally accepted standards has prompted the search for more objective biologic markers. Telomerase is an RNA-containing enzyme associated with immortality in proliferating stem cells and many tumors. We investigated the proliferative activity of 26 ependymomas as determined by MIB-1 immunolabeling and compared the results with the in situ expression of human telomerase RNA (hTR) and WHO tumor grade. The study included 9 WHO grade I ependymomas (6 subependymomas and 3 myxopapillary ependymomas), 13 WHO grade II ependymomas, and 4 anaplastic (WHO grade III) ependymomas. The proliferation index (PI) and telomerase RNA expression were significantly increased in grade III ependymomas (p < 0.0001 for PI and p = 0.0015 for hTR). In these tumors, the PI and hTR expression were highly correlated (p = 0.0001). Of note, a single case designated grade II showed both increased proliferative activity and the highest hTR expression detected in this series of ependymal neoplasms. Our results suggest that the PI and hTR expression may be important biologic markers, independent of other histopathologic criteria of tumor grade. Future studies examining the correlation of MIB-1 cell kinetics and hTR expression with clinical parameters in selected ependymoma subtypes are needed to determine the prognostic relevance of these markers.

Adolescent↗
PubMed1997

Human telomerase RNA expression and MIB-1 (Ki-67) proliferation index distinguish hemangioblastomas from metastatic renal cell carcinomas.

Hemangioblastomas are low-grade, capillary rich neoplasms of the cerebellum and spinal cord that can occur sporadically or in the setting of Von Hippel-Lindau syndrome. The present study analyzed the utility of proliferation potential in differentiating hemangioblastoma from RCC metastatic to the central nervous system using a MIB-1 (Ki-67) labeling index and assessment of expression of the RNA component of telomerase. Immunohistochemical analysis for epithelial membrane antigen (EMA) and MIB-1 was performed on paraffin-embedded sections of 27 hemangioblastomas and 5 RCC metastatic to the central nervous system. All but one hemangioblastoma demonstrated low or negative MIB-1 immunoreactivity, while 4 of 5 RCC metastases had moderate or high labeling indices. Telomerase RNA expression was assessed in 10 hemangioblastomas and in all 5 metastatic RCC by in Situ hybridization. All 10 hemangioblastomas demonstrated a lack of expression of telomerase RNA, while all 5 metastatic RCCs showed moderate to strong expression. Our results suggest that the MIB-1 labeling index is useful in differentiating hemangioblastoma from metastatic RCC and assessment of telomerase expression can also provide novel information on the difference in growth potential of these tumors.

Adolescent↗
PubMed1997

Brain blood flow in the dementias: SPECT with histopathologic correlation in 54 patients.

PURPOSE: To evaluate single photon emission computed tomographic (SPECT) imaging of regional cerebral blood flow in the diagnosis of Alzheimer disease (AD) and the differential diagnosis of the dementias. MATERIALS AND METHODS: Regional cerebral blood flow SPECT was performed with inhaled xenon-133 in 261 patients and with injected technetium-99m hexamethyl-propyleneamine oxime (HMPAO) in 162 patients with possible dementia. In 16 patients, both agents were used in 1 day. SPECT images obtained in elderly healthy control subjects (with Xe-133 in 15, with Tc-99m HMPAO in 14) were available. In each patient without AD, further classification of disease was attempted. Histopathologic correlation was available in 54 patients (with autopsy in 51, with biopsy in three). RESULTS: SPECT diagnoses were true-positive in 37, true-negative in eight, false-positive in three, and false-negative in six patients. Sensitivity was 86% (37 of 43; 95% confidence limits = .72, .95); specificity, 73% (eight of 11; confidence limits = .39, .94); positive predictive value, 92% (37 of 40; confidence limits = .80, .98); and negative predictive value, 57% (eight of 14; confidence limits = .29, .82). CONCLUSION: Regional cerebral blood flow SPECT may assist in the early and late diagnoses of AD and in the differential-diagnosis of the dementias when there is a complicated or confusing clinical picture.

Aged↗
PubMed1996

Case mix in the "downsizing" state hospital.

OBJECTIVE: The study examined whether local variations in levels of community-based services affect the case mix of state hospitals undergoing census reduction. METHODS: Trends in case mix over a 14-year period were analyzed at two Massachusetts state hospitals, one of which underwent more rapid census reduction due to expanded community resources in the catchment area it served. Data on patients' hospital use and on sociodemographic and diagnostic characteristics obtained from 1977, 1986, and 1991 assessments of the hospitals' populations were compared. These time points represented the beginning, midpoint, and end of the census reduction period. Data from 1991 on patients' behavioral and functional status were also examined. RESULTS: Parallel trends on many dimensions were evident at the two hospitals as their censuses fell. By 1986 the hospital operating in the area with greater community services had fewer elderly and long-stay patients but a higher number of admissions per patient. In 1991 this hospital's population also had more patients with high-risk violent behaviors and lower levels of functioning. CONCLUSIONS: Although alternative treatment settings allow diversion of many types of patients from state hospitals, expanded community-based services and alternative inpatient beds have not diverted some patient subgroups, including recidivists and patients with behaviors that present risks in other settings. Plans for meeting the clinical needs and behavioral challenges posed by such patients must be part of any further deinstitutionalization or privatization efforts.

Adolescent↗
PubMed1995

Benzoic acid inhibitors of influenza virus neuraminidase.

A strategy was developed to design non-carbohydrate inhibitors of influenza virus neuraminidase. Using an iterative cycle of modeling, synthesis, biological testing and X-ray crystallography structure determination, a series of inhibitors based on benzoic acid were produced. The refined structures of three compounds complexed with neuraminidase are reported. The results demonstrate the success of this structure-based drug-design strategy.

Journal Article↗
PubMed1995

A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies.

A phosphonate analog of N-acetyl neuraminic acid (PANA) has been designed as a potential neuraminidase (NA) inhibitor and synthesized as both the alpha (ePANA) and beta (aPANA) anomers. Inhibition of type A (N2) and type B NA activity by ePANA was approximately a 100-fold better than by sialic acid, but inhibition of type A (N9) NA was only ten-fold better than by sialic acid. The aPANA compound was not a strong inhibitor for any of the NA strains tested. The crystal structures at 2.4 A resolution of ePANA complexed to type A (N2) NA, type A (N9) NA and type B NA and aPANA complexed to type A (N2) NA showed that neither of the PANA compounds distorted the NA active site upon binding. No significant differences in the NA-ePANA complex structures were found to explain the anomalous inhibition of N9 neuraminidase by ePANA. We put forward the hypothesis that an increase in the ePANA inhibition compared to that caused by sialic acid is due to (1) a stronger electrostatic interaction between the inhibitor phosphonyl group and the active site arginine pocket and (2) a lower distortion energy requirement for binding of ePANA.

Binding Sites↗
PubMed1995

Mothers with severe mental illness caring for children.

This research identifies and describes the Massachusetts population of Department of Mental Health (DMH) case-managed women with severe mental illness who are caretakers of their minor children (N = 314), and compares their demographic and clinical characteristics and service utilization with those of a matched, randomly selected group of DMH case-managed noncaretaking women (N = 328) using the Client Tracking System database. Caretakers were significantly younger, had less formal education, and had higher rates of marriage than did noncaretakers. They are diagnosed more often with major affective disorders and less often with psychotic disorders. Caretakers demonstrate higher levels of functioning and are less likely to have a representative payee. Although caretakers function better, the groups do not differ significantly in their use of DMH services. This is the first systematic, statewide effort to specify the unique characteristics of this substantial group of women with severe mental illness who are caring for their children.

Adaptation, Psychological↗
PubMed1995

Increased tolerance to annual ryegrass toxicity in sheep given a supplement of cobalt.

To determine whether oral cobalt supplements could modify the clinical onset of annual ryegrass toxicity, groups (n = 5) of sheep were dosed orally with 0, 4 or 16 mg cobalt/day. After 3 weeks on this treatment, toxic ryegrass seed was added to their feed to provide 0, 0.15 and 0.30 mg corynetoxins/kg body weight, daily. Sheep receiving cobalt ingested 30% more toxin than did unsupplemented sheep before clinical signs developed (P = 0.03). There was no significant difference between groups receiving 4 and 16 mg cobalt. The results showed that cobalt delayed, but did not prevent, the onset of clinical signs of annual ryegrass toxicity.

Administration, Oral↗
PubMed1995

Factors associated with admission to public and private hospitals from a psychiatric emergency screening site.

OBJECTIVE: The study examined factors associated with admission to public and private hospitals from a mental health care emergency screening system operating under a longstanding mandate to maximize use of private inpatient treatment. METHODS: For 206 patients evaluated at the mental health emergency screening site over a two-and-a-half-month period, data were collected on demographic and clinical characteristics, admission history, services received during the emergency encounter, system variables such as time the patient spent at the emergency screening site, number of admission sites asked to accept the patient, and all reasons cited by providers for refusing to admit the patient. Logistic regression was used to develop a model of factors most likely and least likely to be associated with private hospitalization. RESULTS: Overall, 60 percent of the sample was refused admission by one or more providers, and 55 percent, who were not accepted by and private hospital, became public patients. Private hospital admission was associated with patient or family involvement in referral and disposition, private or Medicaid insurance, a presenting problem of depression or suicidality, and longer time spent at the emergency screening site. Public admission was associated with no insurance, a past history of major public hospitalization, current or past history of assaultiveness, a presenting problem of aggression, and lack of any discharge site. CONCLUSIONS: Private providers are reluctant to admit patients who have characteristics associated with public hospitalization. In the restructuring of health care, a more fully privatized system will likely be called on to absorb such patients. Their care, treatment, and impact on the system should be carefully monitored and evaluated.

Adult↗
PubMed1995

Reflections on visual evoked cortical potentials and selective attention: methodological and historical.

Details of research in which Russ Harter participated in his formative years are reviewed. Harter's participation in the early work on Visual Selective Attention (Eason, Harter & White, 1969) probably contributed most importantly to his career. While reviewing Russ's early experience with basic vision research and pioneer visual evoked potentials (VEPs), there is reference to extensive information regarding stimulus effects on VEPs (exogenous components of the ERP). There can be complex early and late waveforms and waveform changes with changes in certain stimulus conditions. There are critical peripheral vision effects at various loci over the visual field on VEP and reaction time. Special emphasis is given to effects of individual differences in training and skill of experienced subjects, as well differences in ability. These observations may suggest methods for optimizing sensitivity of ERPs and possibly some clues toward further understanding of ERPs.

Attention↗
PubMed1994

Structure of influenza virus neuraminidase B/Lee/40 complexed with sialic acid and a dehydro analog at 1.8-A resolution: implications for the catalytic mechanism.

Neuraminidase is one of the two glycoprotein spikes protruding from the influenza virus membrane. We have determined by X-ray crystallography the native structure of B/Lee/40 neuraminidase (NA) and the structures of its crystals soaked with a substrate, N-acetylneuraminyllactose (NANL), and an inhibitor, 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA) at 1.8-A resolution. NANL was hydrolyzed by the crystalline NA to generate the product N-acetylneuraminic acid (NANA, also known as sialic acid), which is still able to bind to NA. In the difference Fourier map of the presumed NA-NANA complex, the moiety bound in the active site had a distorted boat conformation of NANA, but there is no significant electron density for O2. The structure of the bound moiety is not identical to that of chemically synthesized DANA soaked into NA crystals. Prolonged incubation of NANA with NA in solution at room temperature produced only a trace amount of DANA as detected by NMR. On the basis of our studies, a mechanism is proposed for the enzymatic hydrolysis by influenza virus neuraminidase.

Binding Sites↗
PubMed1994

Anomalous binding of radiolabeled oligonucleotide probes to plaques and tangles in Alzheimer disease hippocampus.

Several reports indicate that Alzheimer disease (AD) brain contains elevated levels of heat shock 70 proteins. To determine the cellular localization of the heat shock 70 mRNAs, specific oligonucleotide probes were in situ hybridized to AD and control brains. When oligonucleotides were in situ hybridized to brain sections with no AD neuropathology, hybridization was cell-specific and prior ribonuclease (RNase) treatment of adjacent sections resulted in no hybridization signal. However, in situ hybridization to AD hippocampus resulted in heavy grain deposition over senile plaques and neurofibrillary tangles. Despite altering a number of experimental variables, we observed a similar pattern of grain deposition with most of the oligonucleotides tested, including one oligonucleotide specific for glutamic acid decarboxylase mRNA. In situ hybridization with either an RNA probe for glutamic acid decarboxylase or an oligonucleotide probe specific for 18S rRNA did not show this pattern of grain deposition. In control studies a sense hsc70 oligonucleotide showed no grain deposition in either cerebellum or hippocampus. Sections from AD hippocampus pretreated with RNase prior to in situ hybridization demonstrated enhanced grain deposition with the majority of probes tested. Anomalous in situ hybridization to AD hippocampus was usually eliminated by removing formamide from the posthybridization washes, although post-RNase sticking often remained intense. These findings indicate that artifactual probe binding to senile plaques and neurofibrillary tangles may complicate the analysis of in situ hybridization studies using oligonucleotide probes to determine mRNA distribution in AD brain.

Adult↗
PubMed1994

The effect of zinc deficiency on wool growth and skin and wool follicle histology of male Merino lambs.

The aims of this work were to quantify the requirements of Zn for wool growth in growing male Merino lambs, and to describe the histological lesions of Zn deficiency in skin and wool follicles. Four groups of male Merino lambs (n 4) weighing 22 kg were fed ad lib. for 96 d on diets that contained 4 (basal diet), 10, 17 or 27 mg Zn/kg. Sheep in a fifth group were fed on the diet containing 27 mg Zn/kg, but were pair-fed to sheep on the 4 mg Zn/kg diet. Zn was added to the basal diet as ZnSO4 to give the respective treatment concentrations. Sheep fed on the diet containing 4 mg Zn/kg showed clinical signs of Zn deficiency and lower feed intakes and wool growth than sheep in the other groups. Their wool fibres were improperly keratinized and the wool follicles contained a higher proportion of apoptotic bodies than other groups. There was no evidence of parakeratosis and the rate of bulb-cell production was not affected. Sheep from other groups showed no clinical signs of Zn deficiency, and mean feed intakes and growth rates did not differ significantly between sheep fed on diets containing 10, 17 or 27 mg Zn/kg. However, wool growth was reduced in sheep fed on the diet containing 10 mg Zn/kg compared with those fed on diets containing 17 or 27 mg/kg. The mean concentration of Zn in the plasma at which wool growth was 90% of maximum was 0.5 mg/l. The equivalent value for the diet was 12 mg/kg, with 95% confidence intervals of 8 to 16 mg/kg. The results suggest that Zn deficiency reduces wool growth through a specific mechanism, perhaps involving impaired protein synthesis.

Animals↗
PubMed1994

Effects of dietary zinc deficiency on the reproductive system of young male sheep: testicular growth and the secretion of inhibin and testosterone.

The effects of dietary zinc deficiency on testicular development in young Merino rams (initial live mass, 22 kg) were tested. Four groups of five rams were fed ad libitum with diets containing 4, 10, 17 or 27 micrograms Zn g-1. To control the effects of loss of appetite caused by zinc deficiency, a fifth group (pair-fed control) was fed the diet containing 27 micrograms Zn g-1, but the amount of feed offered was restricted to that eaten voluntarily by the zinc deficient (4 micrograms Zn g-1) rams they were paired with. After 96 days on the diets, epididymal and testicular masses did not differ significantly between the animals fed 10, 17 or 27 micrograms Zn g-1 ad libitum, but were significantly lower in pair-fed controls, and lowest in the zinc-deficient animals. Testicular responsiveness to LH, as measured by testosterone production, increased substantially in most rams as the experiment progressed, the only exception being the zinc-deficient group, in which the response to LH was lower than in any of the other groups. Testicular concentrations of zinc and testosterone were lower in the zinc-deficient animals than in all the other groups. Plasma inhibin concentrations fell as the experiment progressed in rams fed 17 and 27 micrograms Zn g-1 ad libitum, but not in the other groups. The pair-fed control rams had smaller seminiferous tubules and less lumen development than did the controls fed ad libitum (27 micrograms Zn g-1), which were similar to the animals fed 10 or 17 micrograms Zn g-1. In zinc-deficient rams, the tubule development was further retarded and the interstitial regions were more extensive than in the other groups. We conclude that the overall effect of zinc deficiency on testicular development is due to a combination of a non-specific effect (low gonadotrophin concentrations caused by the low feed intake) and a specific effect due to the lack of zinc. The zinc-specific effect is localized within the testis where it reduces the development of the capacity to produce testosterone, leading to low intratesticular concentrations of testosterone, a critical factor for the growth, development and function of the seminiferous tubules.

Animals↗