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Biomedical subjects

B Waters

Publications and source records attributed to B Waters.

At least 37 records · Page 2Linked to original sources

Exclusion of close linkage of bipolar disorder to dopamine D1 and D2 receptor gene markers.

A potential role of dopamine in bipolar disorder has been suggested by several strands of evidence, namely the ability of dopaminergic agonists to induce mania and the effects of lithium, carbamazepine and the antipsychotics on central dopamine receptors and/or turnover. We therefore aimed to determine if bipolar disorder in two large bipolar pedigrees was linked to the recently cloned dopamine D1 (DRD1) and D2 (DRD2) receptors. (These have been mapped to chromosomal regions 5q35.1 and 11q22.3-q23, respectively). Linkage of bipolar disorder and recurrent depression to DRD1 and DRD2 was tested using a series of genetic models with varying penetrance levels. Additionally, linkage was examined using a series of levels of definitions of affective status (ranging from bipolar I alone to all affective illnesses). Close linkage to these markers was strongly excluded using each model and definition. The findings for DRD1 also persisted when a wide range of rates of 'sporadic' (non-genetic) presentations of illness were incorporated in the analysis, but the DRD2 results did not remain statistically significant at high sporadic rates. The exclusion of linkage to DRD2 is consistent with other recent reports.

Adolescent↗

Effect of nutritional status on organic anion clearance by the swine liver.

Hepatic dysfunction follows a wide range of insults. Impaired excretion of organic dyes such as bilirubin often occurs before other obvious clinical defects in metabolic processes. Indocyanine green (ICG) is excreted through pathways similar to those of bilirubin. To determine the effectiveness of ICG as a marker of hepatic dysfunction related to clinical malnutrition, pigs received 5 mg/kg ICG with simultaneous sampling from the hepatic vein, pulmonary artery, and aorta over 3 hours. Group I remained well nourished, group II was fasted to a weight loss equal to 20% of initial body weight, and group III was fasted to a 20% weight loss and then refed until the animals regained their initial weight. Both systemic and intrinsic hepatic clearance were depressed significantly with fasting but returned above baseline after refeeding. No significant difference appeared between systemic and intrinsic hepatic clearance. Extraction ratios were low in all groups. In outbred swine, ICG clearance reflects the function of hepatic organic anion excretion in vivo, and venous sampling reflects intrinsic hepatic clearance. The impairment of the carrier-mediated transport system is reversible with refeeding.

Animal Feed↗

Close linkage of bipolar disorder to chromosome 11 markers is excluded in two large Australian pedigrees.

The relationship between bipolar disorder and chromosome 11 markers remains uncertain. Whilst re-analysis of the Amish pedigree weakened previous evidence for close linkage (but could not exclude the possibility of genetic heterogeneity), a recent French study has found a significant association between this condition and tyrosine hydroxylase polymorphisms. We aimed to determine if bipolar disorder in two large Australian pedigrees (of Irish and English extraction respectively) was linked to these markers. Of the 84 family members available for testing, nine were diagnosed as bipolar I, one as bipolar II and six had recurrent unipolar depression. Linkage of bipolar disorder and recurrent depression to the chromosome 11p15 markers c-Harvey ras, insulin and tyrosine hydroxylase was tested using a series of genetic models with varying penetrance levels. Additionally, linkage was examined using a series of levels of definitions of affective status (ranging from bipolar I alone to all affective illnesses). Close linkage to these markers was strongly excluded using each model and definition. The findings also persisted when a wide range of rates of 'sporadic' (non-genetic) presentations of illness were incorporated in the analysis. These results are consistent with other recent studies indicating that bipolar disorder is not linked to chromosomal region 11p15.

Adolescent↗

Thermal denaturation of the Ca2(+)-ATPase of sarcoplasmic reticulum reveals two thermodynamically independent domains.

Inactivation of Ca2+ uptake and ATPase activity of the Ca2(+)-ATPase of rabbit sarcoplasmic reticulum was measured and compared to the thermal denaturation of the enzyme as measured by differential scanning calorimetry (DSC) and fluorescence spectroscopy. Two fluorophores were monitored: intrinsic tryptophan (localized in the transmembrane region) and fluorescein isothiocyanate (FITC)-labeled Lys-515 (located in the nucleotide binding domain). Inactivation, defined as loss of activity, and denaturation, defined as conformational unfolding, were irreversible under the conditions used. Activation energies (EA) and frequency factors (A) for inactivation were obtained for the enzyme in 1 mM EGTA and 1 mM Ca2+. These were transformed to a transition temperature for inactivation, Tm (defined as the temperature of half-inactivation when temperature is scanned upward at 1 degree C/min). All denaturation profiles were fit with an irreversible model to obtain EA and Tm for each transition, and the values of these parameters for denaturation were compared to the values for inactivation. In EGTA, denaturation obeys a single-step model (Tm = 49 degrees C), but a two-step model is required to fit the DSC provile of the enzyme in 1 mM Ca2+. The specific locations of tryptophan and the fluorescein label were used to demonstrate that denaturation in Ca2+ occurs through two distinct thermodynamic domains. Domain I (Tm = 50 degrees C) consists of the nucleotide binding region and most likely the phosphorylation and transduction regions [MacLennan, D. H., Brandl, C. J., Korczak, B., & Green, N. M. (1985) Nature 316, 696-700].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Increased thermostability of thermotolerant CHL V79 cells as determined by differential scanning calorimetry.

Heat shock denatures cellular protein and induces both a state of acquired thermotolerance, defined as resistance to a subsequent heat shock, and the synthesis of a category of proteins referred to as heat-shock proteins (HSPs). Thermotolerance may be due to the stabilization of thermolabile proteins that would ordinarily denature during heat shock, either by HSPs or some other factors. We show by differential scanning calorimetry (DSC) that mild heat shock irreversibly denatures a small fraction of Chinese hamster lung V79-WNRE cell protein (i.e., the enthalpy change, which is proportional to denaturation, on scanning to 45 degrees C at 1 degree C/min is approximately 2.3% of the total calorimetric enthalpy). Thermostability, defined by the extent of denaturation during heat shock and determined from DSC scans of whole cells, increases as the V79 cells become thermotolerant. Cellular stabilization appears to be due to an increase in the denaturation temperature of the most thermolabile proteins; there is no increase in the denaturation temperatures of the most thermally resistant proteins, i.e., those denaturing above 65 degrees C. Cellular stabilization is also observed in the presence of glycerol, which is known to increase resistance to heat shock and to stabilize proteins in vitro. A model is presented, based on a direct relationship between the extent of hyperthermic killing and the denaturation or inactivation of a critical target that defines the rate-limiting step in killing, which predicts a transition temperature (Tm) of the critical target for control V79-WNRE cells of 46.0 degrees C and a Tm of 47.3 degrees C for thermotolerant cells. This shift of 1.3 degrees C is consistent with the degree of stabilization detected by DSC.

Animals↗

The teaching of dento-maxillo-facial radiology in Australian dental schools.

The skills necessary to successfully perform radiological procedures in general dental practice are described and should be used as criteria when developing an effective undergraduate curriculum and as determinants of the contents of continuing education programmes. The present status of undergraduate curricula. continuing education, and postgraduate programmes as well as the recognition of the specialized nature of dento-maxillo-facial radiology, are discussed and recommendations for future developments are made.

Australia↗

Cognitive effects of cranial irradiation in leukaemia: a survey and meta-analysis.

Central nervous system (CNS) prophylaxis involving cranial irradiation has frequently been found to result in cognitive deficits in survivors of childhood acute lymphoblastic leukaemia. The existence of this effect is still controversial, however, as is the question of factors that might affect its severity. The literature is surveyed and a meta-analysis undertaken on 30 IQ comparisons, which shows a substantial average decrement in irradiated subjects. The effect is larger when radiation is administered at a younger age and appears to be progressive. The effect may comprise two elements, one common to young cancer patients and one specific to CNS prophylaxis.

Brain↗

Validation of the Children's Depression Scale and the Children's Depression Inventory in a prepubertal sample.

The validity of the Children's Depression Scale (CDS), the Children's Depression Inventory (CDI) and their respective parent report versions was assessed in a sample of outpatient and normal control prepubertal children. Scores from the child and parent versions of both scales significantly discriminated between children independently diagnosed as depressed and those with nondepressive disorders. Both measures also distinguished depressed and dysphoric children. Contrary to the findings of earlier studies, a significant rate of agreement was found between the reports provided by the children and their parents. The results suggest that the influence of the child's age and clinical status on reporter correspondence patterns should be considered more exhaustively in future research.

Child↗

A linkage study of primary affective disorder.

Marker loci in 113 members of nine unrelated multiplex families identified by a bipolar proband were tested for linkages with primary affective disorder. Linkage was excluded between the disease locus (assuming that it was a single autosomal dominant gene) and the HLA loci at a recombination fraction of 0.2, the ABO, Rh, and Lu loci at almost 0.05 and the Fy and P loci at 0.001.

Adult↗

Oculomasticatory myorhythmia: a unique movement disorder occurring in Whipple's disease.

We describe two patients and a previously reported patient who acquired unique pendular vergence oscillations of the eyes and concurrent contractions of the masticatory muscles, i.e., oculomasticatory myorhythmia (OMM). The smooth disjunctive eye movements cycled with a frequency of 0.8 to 1.2 Hz. An analysis of peak velocities (15 to 200 degrees/sec) with respect to peak amplitudes (5 to 25 degrees) revealed dynamics characteristic of normal vergence movements. The pathological alterations resulting in pendular vergence oscillations implicate a separately functioning, physiologically normal vergence system within the brainstem. In addition to paralysis of vertical gaze, each patient also experienced progressive somnolence and intellectual deterioration. An intestinal biopsy in 1 patient established a diagnosis of Whipple's disease, which led to appropriate treatment and amelioration of the OMM. A pathological diagnosis of Whipple's disease of the central nervous system was made in the other 2 patients; results of an intestinal biopsy in one of these patients were normal. No patient had palatal myoclonus, and olivary pseudohypertrophy was not found in two autopsy examinations. Thus, OMM is a distinct movement disorder and has been recognized only in Whipple's disease. We conclude that patients with OMM should be treated presumptively for Whipple's disease of the central nervous system, even if a jejunal biopsy is normal.

Eye Movements↗

Electron spin resonances of a living system (Drosophila) on normal and carcinogenic diets.

This investigation was a study of the free radical concentration of a living system, Drosophila melanogaster, by electron spin resonance spectroscopy. The paramagnetic content of the organism was measured as a function of age, mutant strain, and diet (normal vs. carcinogenic). In all cases, 4 to 6 days after ecdysis the free radical concentration decreased to approximately 70% of its value as measured shortly after ecdysis. The different mutant strains exhibited distinctly different free radical concentrations in accord with visual observations of the degree of pigmentation. Drosophila raised on a carcinogenic diet always showed a lower concentration of free radicals than the control groups on a normal diet.

Animals↗

Assortative mating for major affective disorder.

The families of 26 married bipolar manic depressives were examined in detail. The rate of affective disorder in their spouses, and the parents and siblings of their spouses, was ascertained. The prevalence of affective disorder among the parents and siblings and of the spouses of age- and social class-matched schizophrenics and well controls was also ascertained. Finally, the prevalence of affective and other psychiatric disorders in the adult offspring of the bipolar probands was ascertained and related to the presence or absence of affective disorder in the spouse. We did not find clear evidence of assortative mating for major affective disorder, although dual mating for affective disorder had the expected result of increasing the risk for affective disorder in the adult offspring.

Alcoholism↗

Erythrocyte lithium transport variables as a marker for manic-depressive disorder.

This study examines whether variability in the efflux of lithium from erythrocytes may be a marker for manic-depressive disorder in related individuals. The subjects of the study were 73 individuals from 12 families in which there was more than one bipolar manic-depressive member. Using an in vitro procedure, we subjected erythrocytes to four conditions which are believed to inhibit lithium efflux. Only phloretin, an inhibitor of Na+-Li+ countertransport, produced significant inhibition. Variability in this inhibition was not related to the presence or absence of manic-depressive disorder, although it was related to family membership. The implications of these findings are discussed.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

The effect of juvenile-onset manic-depressive disorder on the developmental tasks of adolescence.

The impact on the individual of manic-depressive disorder can be devastating. This is most evident in adolescence, an epoch during which many cases first declare themselves. Adolescence is a crucial developmental phase during which confidence, initiative, and sociability are consolidated. Core symptoms of manic-depressive disorder involve all these functions, and appropriate adolescent development can be further undermined by the knowledge that these same functions can be driven out of control by the illness. An illustrative case of an articulate young lady suffering from manic-depression is described, and her feelings about the uncertainty introduced into her life by the illness are compellingly presented in a poem. The major implication of our observations is that adolescent-onset manic-depressives need not be burdened additionally by developmental arrest or delay. They frequently need psychotherapy to adjust to the handicap of their illness.

Adolescent↗