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Biomedical subjects

S A Smith

Publications and source records attributed to S A Smith.

At least 19 recordsLinked to original sources
PubMed1992

New 'phantom' dinoflagellate is the causative agent of major estuarine fish kills.

A worldwide increase in toxic phytoplankton blooms over the past 20 years has coincided with increasing reports of fish diseases and deaths of unknown cause. Among estuaries that have been repeatedly associated with unexplained fish kills on the western Atlantic Coast are the Pamlico and Neuse Estuaries of the southeastern United States. Here we describe a new toxic dinoflagellate with 'phantom-like' behaviour that has been identified as the causative agent of a significant portion of the fish kills in these estuaries, and which may also be active in other geographic regions. The alga requires live finfish or their fresh excreta for excystment and release of a potent toxin. Low cell densities cause neurotoxic signs and fish death, followed by rapid algal encystment and dormancy unless live fish are added. This dinoflagellate was abundant in the water during major fish kills in local estuaries, but only while fish were dying; within several hours of death where carcasses were still present, the flagellated vegetative algal population had encysted and settled back to the sediments. Isolates from each event were highly lethal to finfish and shellfish in laboratory bioassays. Given its broad temperature and salinity tolerance, and its stimulation by phosphate enrichment, this toxic phytoplankter may be a widespread but undetected source of fish mortality in nutrient-enriched estuaries.

Animals↗
PubMed1992

Genetic heterogeneity of early-onset familial breast cancer.

A gene for early-onset familial breast cancer has recently been mapped to the chromosome 17q12-23 region. In order to confirm the gene location, we have tested an extensive early-onset breast cancer family with 4 markers in this chromosome region. Linkage was negative with all 4 markers. This study suggests that there is genetic heterogeneity among early-onset breast cancer families.

Base Sequence↗
PubMed1992

SCM4, a gene that suppresses mutant cdc4 function in budding yeast.

The gene SCM4 encodes a protein which suppresses a temperature-sensitive allele of the cell division cycle gene CDC4 in Saccharomyces cerevisiae. SCM4 was cloned on a 1.8 kb BamHI fragment of yeast genomic DNA in the high copy-number vector pJDB207, which results in a 50- to 100-fold increase in the level of the 700 nucleotide SCM4 transcript in vivo. The SCM4 gene encodes a 20.2 kDa protein of 187 amino-acids with a clear tripartite domain structure in which a region rich in charged residues separates two domains of largely uncharged amino acids. Although the apparent allele specificity of cdc4 suppression suggests that the CDC4 and SCM4 proteins interact, disruption of SCM4 demonstrates that the gene product is not essential for mitosis or meiosis; however, it may be a member of a family of related, functionally redundant proteins.

Alleles↗
PubMed1992

Variation in the antigenic characteristics of venom from the Mojave rattlesnake (Crotalus scutulatus scutulatus).

Venoms from 31 specimens of the Mojave rattlesnake (Crotalus scutulatus scutulatus) were examined to further characterize reported differences among venoms of this species. Twenty-two venoms were recognized by a monoclonal antibody to Mojave toxin, CSS12. Nine venoms were recognized by CA-P-8, a monoclonal antibody produced against the hemorrhagic venom of C. atrox. Seven of these produced strong hemorrhage in mice and were also recognized by polyclonal antibodies (anti-F5) produced against a fraction of Mojave rattlesnake venom that inactivates serum complement. Fractionated venom revealed that CA-P-8 and anti-F5 recognized different proteins. Two of the venoms recognized by CA-P-8 were not recognized by anti-F5 and produced minimal hemorrhage in mice. This suggests that more than one factor may be necessary to induce strong hemorrhage.

Animals↗
PubMed1992

Development of an enzyme-linked immunosorbent assay (ELISA) for the detection of antibody to the parasitic dinoflagellate Amyloodinium ocellatum in Oreochromis aureus.

An enzyme-linked immunosorbent assay (ELISA) using antibody to affinity-purified Oreochromis aureus immunoglobulin and antigens from the parasitic dinoflagellate amyloodinium ocellatum was developed. The ELISA was then used to evaluate the immune response of the tilapine fish to immunization with the parasite. Fish immunized with antigens of the dinospore stage, either live or sonicated, produced a specific immune response that was detectable by this ELISA. Combinations of serial dilutions of A. ocellatum antigen and fish anti-A. ocellatum serum were examined to determine which dilutions provided optimal differentiation of seropositive from seronegative fish. Fresh and heat-inactivated serum from both seropositive and seronegative fish produced similar results.

Animals↗
PubMed1992

The use of indirect memory tests to assess malingered amnesia: a study of metamemory.

Many techniques have been suggested for identifying criminal suspects who are simulating amnesia for the events surrounding a crime. The present research focuses on indirect memory tests as a potential means of discriminating between those who genuinely suffer from amnesia and those who are simulating. Subjects studied a list of words and subsequently performed either a word completion or a fragment completion task. Under normal indirect test instructions, typical priming effects were observed. When subjects were motivated to simulate amnesia for the list, target completion rates were consistently, and sometimes reliably, below baseline completion rates. This finding is contrary to the performance of genuine amnesics, whose performance on indirect tests typically mirrors that of normal subjects. Indirect tests may prove useful in discriminating genuine and simulating amnesics.

Adult↗
PubMed1992

Allele losses in the region 17q12-21 in familial breast and ovarian cancer involve the wild-type chromosome.

A predisposing gene for breast and ovarian cancer has recently been mapped to chromosome 17q12-21. If this gene is a tumour suppressor gene, allele losses would be expected in the tumours of affected family members and the losses should affect the wild-type chromosome, reflecting the need for inactivation of the wild-type allele at the predisposing locus. In four multiple case breast-ovarian cancer families, we have found that in each of nine tumours which showed allele losses, the losses were from the wild-type chromosome. This suggests that the putative 'breast-ovarian' cancer gene is indeed a tumour suppressor gene.

Alleles↗
PubMed1992

BRL 35135, a potent and selective atypical beta-adrenoceptor agonist.

BRL 35135, via its active deesterified metabolite BRL 37344, is a potent example of a new group of beta-adrenoceptor agonists that stimulate selectively a novel beta adrenoceptor that was originally shown to be present in brown adipose tissue in rodents. BRL 35135 produces a dose-related increase in energy expenditure in rodents and, in genetically obese (ob/ob) mice, a dose of 0.5 mg.kg-1.d-1 has significant antiobesity activity. This weight loss is entirely due to loss of fat; muscle protein is preserved. In studies in nonobese men, BRL 35135 (0.1 mg/kg) increased both resting metabolic rate and the thermic response to a glucose load. BRL 35135 is effective in improving glucose tolerance in genetically obese (ob/ob) mice and obese Zucker (fa/fa) rats at doses that have no significant antiobesity activity. The improved glucose tolerance is the result of significant improvement in insulin sensitivity. In 10-d studies in obese and diabetic patients, BRL 35135 produced improvements in glucose tolerance and insulin sensitivity.

Adipose Tissue, Brown↗
PubMed1992

The humeroscapular bone of the great horned owl (Bubo virginianus) and other raptors.

A small, separate, bony density dorsal to the shoulder joint is radiographically visible in several species of large hawks and owls. Gross dissection and histological examination show the bone to lie on the deep surface of the major deltoid muscle in intimate association with the dorsal coracohumeral ligament of the shoulder joint. The tendon of the supracoracoideus muscle passes immediately cranial to the humeroscapular bone. Two ligaments distinct from the shoulder joint capsule attach the humeroscapular bone to the proximal humerus: one passes to the proximal edge of the pectoral crest of the humerus, and the other passes to the ventral tubercle of the humerus. The bone was described as the humeroscapular bone in reference to a similar fibrocartilaginous structure possessed by some birds. The humeroscapular bone is present in the great horned owl (Bubo virginianus), the screech owl (Otus asio), the barred owl (Strix varia), the red-tailed hawk (Buteo jamaicencis), the Cooper's hawk (Accipiter cooperii), and the sharp-shinned hawk (Accipiter striatus). The bone is absent in the barn owl (Tyto alba), the osprey (Pandion haliaetus), the golden eagle (Aquila chysaetos), and the turkey vulture (Cathartes aura), though some of these species possessed a similar fibrocartilaginous structure. Whether the humeroscapular structure develops as bone or cartilage in a given species may be related to other morphological features of the wing, and/or to characteristics of the predatory behavior of the species. Clinicians and anatomists dealing with birds of prey must be aware of the presence of the humeroscapular bone to avoid misinterpreting it as a fracture fragment.

Animals↗
PubMed1991

Evidence for major gene transmission of developmental dyslexia.

OBJECTIVE: --There is strong evidence that developmental dyslexia is both familial and heritable, but the mode of genetic transmission has remained unclear. In this article, we examine specific genetic hypotheses about the mode of transmission of developmental dyslexia by performing complex segregation analyses. DESIGN: --A family study method was applied, whereby the relatives of dyslexic probands were examined for dyslexia. The families studied represent four independently ascertained samples. SETTING: --The four samples of families were primarily from rural and suburban communities of Colorado, Washington State, and Iowa. PARTICIPANTS: --A total of 204 families and 1698 individuals in the four samples combined. MAIN OUTCOME MEASURES: --The complex segregation program, POINTER, was used to test competing genetic hypotheses of how a categorical trait (dyslexia) is transmitted in families. RESULTS: --The results were consistent with major locus transmission in three of four samples and with polygenic transmission in the fourth. In these three samples, the estimates of penetrance for the AA, Aa, and aa genotypes (where A is the abnormal allele) were, respectively, 1.000, 1.000, and 0.001 to 0.039 in males, and 0.560 to 1.000, 0.550 to 0.897, and 0.000 in females. The estimated gene frequency of the major locus was between 3% and 5%. CONCLUSIONS: --Sex-influenced, additive, or dominant transmission occurs in a significant proportion of dyslexic families. Other evidence indicates, however, that dyslexia is etiologically heterogeneous and that there is genetic heterogeneity even among families selected for apparent dominant transmission. Thus, while no single major locus may account for all of dyslexia, it is important to pursue potential major loci for dyslexia using linkage techniques.

Adult↗
PubMed1991

Cholesterol metabolism in hypercholesterolemia-resistant rabbits.

Normal rabbits typically respond to a diet high in cholesterol with a large increase in the concentration of plasma cholesterol. We have previously described the breeding and partial characterization of a variant rabbit which does not respond to a high cholesterol diet with changes in plasma cholesterol concentration. In the present report we have characterized three components involved in cholesterol homeostasis: the B/E (LDL) receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase activity (HMG-CoA reductase, EC 1.1.1.34) and acyl-coenzyme A: cholesterol acyltransferase activity (ACAT, EC 2.3.1.26) in the livers of the hypercholesterolemia-resistant rabbits. Using normal cholesterol-fed rabbit [125I] beta-VLDL as a ligand, liver membranes prepared from resistant rabbits fed a low-cholesterol diet had 70% higher binding capacity than membranes from normal rabbits fed the same diet. Similar experiments demonstrated that the resistant rabbits had a 240% higher B/E receptor binding capacity compared to normal animals when liver membranes were prepared from animals fed a 0.25% cholesterol-enriched diet. No difference in the binding affinity of [125I]beta-VLDL was detected in membranes prepared from normal or resistant animals. When fed a low-cholesterol diet, the resistant rabbits had approximately 2-fold higher hepatic HMG-CoA reductase activity (97.4 +/- 3.5 pmol product/mg/min in resistant animals compared to 45 +/- 1.1 pmol product/min/mg in normal animals). The difference was exaggerated in animals fed the 0.25% cholesterol-enriched diet, 73.3 +/- 5.5 vs 2.4 +/- 0.56 pmol product/min/mg for resistant and normal membranes respectively. The basal activity of ACAT in hepatic membranes was significantly lower in the resistant rabbits compared to normal rabbits (138 +/- 11 vs 268 +/- 19 pmol cholesteryl ester/min/mg in resistant and normal rabbits respectively); when fed a 0.25% cholesterol-enriched diet, the enzyme was induced 6-fold in normal animals but was increased only 2-fold in the resistant animal. These biochemical data suggested that the resistant rabbit maintained low intracellular cholesterol even when fed a cholesterol-enriched diet. Direct measurement of cellular cholesterol and cholesteryl esters demonstrated that the concentration of these lipids was significantly lower in the resistant animal than in normal animals with the largest differences found in the cytoplasmic rather than the membrane compartment. These studies demonstrate that the resistant rabbit manifests several quantitative differences in cholesterol metabolism and in the regulation of cholesterol metabolism; but these studies do not directly explain the underlying cause of the resistance to hypercholesterolemia in the resistant rabbit.

Animals↗
PubMed1991

Relationships among black families' cardiovascular disease risk factors.

BACKGROUND: As participants in the District of Columbia Studies of Children's Activity and Nutrition (D.C. SCAN), 262 black mothers and two of each mother's children (3-4 and 8-10 years of age) were measured in their homes for selected cardiovascular disease risk factors: serum total cholesterol, systolic and diastolic blood pressures, height and weight for body mass index, fitness (sum of pulses), activity, and triceps and subscapular skinfolds. RESULTS: For each measure, mothers in the highest quartile were more likely to have children who were also in the highest quartile, and mothers in the lowest quartile were more likely to have children who were in the lowest quartile. For the physiological measures, (with the exception of systolic blood pressure), correlations tended to be stronger between the siblings than between the younger child and the mother, and older siblings' physiological measures contributed to the prediction of younger siblings' physiological measures after controlling for mothers' physiological measures. Relationships between family cardiovascular disease risk factor history and children's serum total cholesterol, and systolic and diastolic blood pressure levels tended to be gender related; i.e., family cardiovascular disease risk factors on the mother's side were more likely to be related to levels among the female but not the male children and vice versa. When personal characteristics were controlled for, the family's cardiovascular disease history was related more strongly to the younger than to the older sibling's systolic and diastolic blood pressure levels. CONCLUSIONS: Results tend to substantiate the importance of screening and counseling other family members, especially a child of the same gender as the parent with a cardiovascular disease or an elevated risk factor level.

Black or African American↗
PubMed1991

Ultrastructure and microanalyses of the protoscolex hooks of Echinococcus granulosus.

The rostellar distal cytoplasm of Echinococcus granulosus protoscoleces is characterized by extensive basal membrane infolding, prominent hemidesmosomes and is subtended by a lamina reticularis with microfibrils of approximately 10 nm diameter that occasionally show a 55 nm banding periodicity. The rostellar hooks, in 2 rows, each have a blade, guard and handle region and possess a central amorphous pulp, a middle microfibrillar medulla with microfibrils of approximately 4 nm diameter, and a complex outer cortex in all but the proximal region of the guard and the base of the handle. In these regions additional material, of similar electron density to the medulla, but lacking the fibrillar substructure, occurs and gives the areas a lobed appearance. Energy-dispersive X-ray microanalysis of whole hooks demonstrated the presence of sulphur and trace quantities of phosphorus. X-ray near-edge absorption spectra resembled those of cystine, feather and hair and showed the sulphur to be predominantly in the form of disulphide linkages. X-ray diffraction patterns of whole hook preparations revealed 2 diffuse rings with equatorial spacings of 7.99 A and 15.22 A, thus differing from vertebrate keratins.

Animals↗
PubMed1991

Pharmacokinetic interaction between propranolol and the HMG-CoA reductase inhibitors pravastatin and lovastatin.

1. Single oral 20 mg doses of the HMG-CoA reductase inhibitors pravastatin and lovastatin, with and without concomitant propranolol (40 mg twice daily), were administered to 16 healthy male subjects participating in a randomized, four-way crossover study. 2. Serum concentrations of total and active inhibitors were measured by bioassay and concentrations of pravastatin, two pravastatin metabolites and lovastatin acid were measured by gas chromatography/mass spectrometry. 3. Coadministration of propranolol with pravastatin reduced the mean area under the serum concentration-time curve (AUC) of total inhibitors by 23%, of active inhibitors by 20% and of pravastatin by 16%. 4. Coadministration of propranolol with lovastatin also resulted in decreases in the mean serum AUC of total inhibitors by 18%, of active inhibitors by 12% and of lovastatin acid by 13%. 5. These decreases in systemic drug concentrations may reflect enhanced drug first-pass hepatic clearance in the presence of propranolol. 6. The clinical significance of these changes is likely to be small.

Adult↗
PubMed1991

Non-cardiac autonomic tests in diabetes: use of the galvanic skin response.

Diabetic peripheral neuropathy affects both large myelinated and small unmyelinated nerve fibres. It has been proposed that the small unmyelinated fibres, responsible for pain and temperature sense, and autonomic function, are involved early, particularly in subjects with painful symptoms, and may be important in foot ulceration. The sympathetic skin response has been used to investigate the function of small unmyelinated sympathetic fibres in the limbs of diabetic subjects. Changes in skin resistance at the fingers and toes have been measured simultaneously after a sound stimulus. These procedures were controlled using a microcomputer. Data collected from 55 diabetic subjects, randomly selected from the diabetic clinic, have been compared with results from conventional tests of large motor and sensory fibres and autonomic function. The ratio of the change in skin resistance for toes to fingers correlated with sural and posterior tibial nerve conduction velocity (correlation coefficients 0.54 and 0.42, p less than 0.001 and p less than 0.01, respectively), with the expired to inspired ratio (correlation coefficient 0.51, p less than 0.01), and inversely with vibration perception threshold in the feet (correlation coefficient 0.50, p less than 0.001). Correlation with the dark adapted pupil diameter, however, only just achieved statistical significance (correlation coefficient 0.27, p = 0.043). We propose that this simple test may elucidate the role of the peripheral autonomic system in diabetic neuropathy.

Diabetic Neuropathies↗
PubMed1991

Central sleep apnoea in congenital muscular dystrophy.

Sleep-disordered breathing may occur in a wide variety of neuromuscular syndromes, and may present with diverse, often isolated, symptoms or findings such as excessive daytime sleepiness, pulmonary hypertension, congestive heart failure, morning headaches, or hypoxia-induced nocturnal seizures. The authors report two sisters with congenital muscular dystrophy in whom central sleep apnoea resulted in the isolated symptom of nocturnal seizures in one, and morning headaches in the other. Review of the literature reveals that sleep-disordered breathing may be common in neuromuscular disorders, and may often be present when clinical weakness is mild, and insufficient to result in diurnal respiratory dysfunction.

Adult↗
PubMed1991

The effect of heterochromatin on synapsis of the sex chromosomes of Peromyscus (Rodentia, Cricetidae).

The pairing behavior of the sex chromosomes in male and female individuals representing seven species of Peromyscus was analyzed by electron microscopy of silver-stained zygotene and pachytene configurations. Six species possess submetacentric or metacentric X chromosomes with heterochromatic short arms. Sex-chromosome pairing in these species is initiated during early pachynema at an interstitial position on the X and Y axes. Homologous synapsis then progresses in a unidirectional fashion towards the telomeres of the X short arm and the corresponding arm of the heterochromatic Y chromosome. The distinctive pattern of synaptic initiation allowed a late-synapsing bivalent in fetal oocytes to be tentatively identified as that of the X chromosomes. In contrast to the other species, Peromyscus megalops possesses an acrocentric X chromosome and a very small Y chromosome. Sex-chromosome pairing in this species is initiated at the proximal telomeric region during late zygonema, and then proceeds interstitially towards the distal end of the Y chromosome. These observations suggest that the presence of X short-arm heterochromatin and corresponding Y heterochromatin interferes with late-zygotene alignment of the pairing initiation sites, thereby delaying XY synaptic initiation until early pachynema. The pairing initiation sites are conserved in the vicinity of the X and Y centromeres in Peromyscus, and consequently the addition of heterochromatin during sex-chromosome evolution essentially displaces these sites to an interstitial position.

Animals↗