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Biomedical subjects

G Shaw

Publications and source records attributed to G Shaw.

At least 199 records · Page 11Linked to original sources
PubMed1988

Primary genetic control of somatic sexual differentiation in a mammal.

The classical view of mammalian sexual differentiation is that a gene on the Y chromosome transforms the indifferent gonad into a testis. The Leydig cells then secrete androgen which stimulates the development of the male reproductive tract, and the Sertoli cells secrete Mullerian inhibitory substance which inhibits the development of the female reproductive tract. In the absence of a testis, the Mullerian duct develops into the Fallopian tubes, uterus and vagina. Thus the whole of sexual differentiation is thought to be hormonally mediated as a consequence of this initial genetic determination of gonadal sex. We have found evidence in a marsupial mammal for extensive sexual dimorphisms which precede any morphological differentiation of the gonads. Thus the classical view of mammalian sexual differentiation may have over-emphasized the role of testicular hormones, and overlooked earlier genetic effects.

Animals↗
PubMed1988

"Rates" of birth defects.

The proportion of children born with a particular defect is not a "birth defect rate" but, rather, a prevalence proportion. The implications of confusing a rate and a proportion are discussed in terms of the interpretation of birth defect data. It is recommended that "prevalence proportion" or "prevalence" be used to report the frequency of various defects rather than the often-used "prevalence rate."

Biometry↗
PubMed1988

Ubiquitin and microtubule-associated protein tau immunoreactivity each define distinct structures with differing distributions and solubility properties in Alzheimer brain.

Several cytoskeletal polypeptides as well as the protein ubiquitin have been implicated as components of the neurofibrillary tangles of Alzheimer disease. We have examined the relationship of ubiquitin staining with immunoreactivity for some of these proteins, both in frozen sections and in cytoskeletal fractions of Alzheimer brain material. We noted (i) antibodies specific solely for neurofilament and glial filament proteins failed to stain the fibrils stainable with ubiquitin. Tau-1 antibody stained some but not all of the ubiquitin-stained profiles; fibers staining only for tau or only for ubiquitin were also seen. (ii) The Tau-1-stained material was rather diffuse and granular, in contrast to the very sharply defined ubiquitin-positive profiles. (iii) When Tau-1 and ubiquitin stain the same fiber, Tau-1 immunoreactivity is often visualized as a diffuse cortical layer of material surrounding a core of ubiquitin immunoreactivity. (iv) The tau immunoreactivity can be almost totally removed by boiling Alzheimer brain cytoskeletal material in 2% NaDodSO4 containing a sulfhydryl reducing agent, this procedure apparently having no effect on the ubiquitin immunoreactivity. If similar material is boiled in 2% NaDodSO4 in the absence of a sulfhydryl reducing agent, the tau immunoreactivity is removed less efficiently, suggesting that tau epitopes are bound to the ubiquitin reactive material in a manner partially dependent on covalent disulfide bridges. These results show that the tau and ubiquitin distributions, both characteristic of Alzheimer disease, are qualitatively different, and that the two markers define immunologically and biochemically distinct structures.

Alzheimer Disease↗
PubMed1988

Müllerian inhibiting substance production and testicular migration and descent in the pouch young of a marsupial.

The ontogeny of Müllerian inhibiting substance (MIS) production by the developing testis of an Australian marsupial, the tammar wallaby (Macropus eugenii), was determined during pouch life using an organ-culture bioassay of mouse fetal urogenital ridge. This information was related to the morphological events during testicular migration and descent. MIS biological activity was found in testes (but not ovaries or liver) of pouch young from 2 to 85 days of age. MIS production had commenced by day 2, which is within a day of the first gross morphological signs of testicular differentiation. Müllerian duct regression occurred between 10 and 30 days, which partly coincided with testicular migration to the inguinal region and enlargement of the gubernacular bulb (15 to 30 days). These observations are consistent with the hypothesis that MIS may be involved in testicular transabdominal migration. The epididymis commenced development and growth only after the testis had descended through the inguinal ring. This provides no support for the suggestion that the epididymis is involved in testicular descent into the scrotum. The basic sequence of events in post-testicular sexual differentiation in the wallaby is sufficiently similar to that seen in eutherian mammals to make it an excellent experimental model for future studies of testicular differentiation, migration and descent.

Animals↗
PubMed1988

Experimental manipulation of sexual differentiation in wallaby pouch young treated with exogenous steroids.

We have investigated the effects of androgen or oestrogen treatment of female or male tammar wallabies from the day of birth, when the gonads are histologically undifferentiated, to day 25 of pouch life, when the gonads and the Wolffian and Müllerian ducts have differentiated and the testes have migrated through the inguinal canal. Female tammars treated with testosterone propionate (24-50 mg kg-1 day-1) orally for 25 days had enlarged Wolffian and Müllerian ducts. Mammary and pouch development, however, was indistinguishable from that of control females. The treatment had no apparent effect on ovarian development, or on ovarian position in the abdomen. The phallus of males and females was similar in size, and neither experimental treatment had a significant effect on its size at day 25. Male tammars treated with oestradiol benzoate (1.2-2.5 mg kg-1 day-1) orally for 25 days had gross hypertrophy of the urogenital sinus. Testicular morphology was abnormal; many of the germ cells appeared necrotic, the seminiferous tubules were of reduced diameter, and there were few Leydig cells and increased amounts of fibrous tissue between the tubules. The cortex of these gonads contained some areas which had an ovarian appearance, lacking tubules and containing numerous germ cells. The Müllerian ducts of control males had regressed, but this was prevented by oestrogen treatment, suggesting an inhibition of either Müllerian Inhibiting Substance (MIS) production or its action. Normal testicular migration was inhibited in treated males; the testes remained high in the abdomen, similar in position to the ovaries of control females, whilst control males all had testes in the inguinal region. The gubernaculum and processus vaginalis of control males extended into the scrotum, but in treated males they terminated outside it. Oestrogen treatment had no effect on the size of the scrotum and did not induce mammary or pouch development. These experiments show that marsupials, like eutherians, have a dual hormonal control of Wolffian and Müllerian development. By contrast, the initial development of the mammary glands, pouch, gubernaculum and scrotum does not appear to be under hormonal control and is therefore likely to be autonomous and dependent on genotype.

Animals↗
PubMed1987

Results using medium supplemented with either fresh or frozen stored serum in human in vitro fertilization.

This study retrospectively compared the success of in vitro fertilization (IVF) among patients whose gametes had been incubated either in medium supplemented with freshly prepared pooled serum (331 cases) or in pooled serum which had been stored at -20 degrees C prior to use (728 cases). Frozen stored serum was as effective as fresh serum with regard to the proportion of oocytes which fertilized and embryos which implanted and was not associated with any increased incidence of fetal loss during postimplantation development.

Blood Physiological Phenomena↗
PubMed1987

Dedifferentiation of cultured thyroid cells by epidermal growth factor: some insights into the mechanism.

Epidermal growth factor (EGF) has been shown to enhance both the proliferation and dedifferentiation of thyroid cells in culture, leading to a maintained dedifferentiated state, even in the presence of thyrotropin (TSH). Since this maintained loss of differentiated function is not seen with other mitogens, it may relate to a regulatory role for EGF in thyroid function. Therefore, we have examined the loci affected by the dedifferentiative actions of EGF using porcine thyroid cells in culture. EGF (10 ng/ml) induces a loss of thyrotropin (TSH) receptors with a time course identical to the loss in ability to transport iodide. This could account for the difference in extent of iodide uptake and morphological dedifferentiation seen between TSH- and cAMP-supported cells, although the fact that cAMP-supported cells also dedifferentiate implies a lesion distal to the cyclase. Reciprocal plot analysis of iodide uptake in control and EGF-treated cells shows that EGF increases the Km for iodide transport, corresponding to a decreased affinity of iodide pump sites for iodide. These effects on iodide pump affinity and TSH receptor number may result from reversal of thyroid cell polarity in monolayer culture, or they may be the result of more specific actions of EGF at these loci. It has been possible to discriminate between the proliferative and dedifferentiating actions of EGF using amiloride, a non-specific inhibitor of the Na+/H+ antiporter. An optimum concentration of amiloride (0.1 mM) was able to block EGF-stimulated incorporation of [3H]thymidine into DNA without preventing the blockade of iodide uptake, which implies that dedifferentiation is not a consequence of proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1987

Isolation and partial purification of an enzyme catalyzing the formation of O-xylosylzeatin in Phaseolus vulgaris embryos.

An enzyme catalyzing the formation of a cytokinin metabolite, an O-pentosyl derivative of zeatin [Lee, Y. H., Mok, M. C., Mok, D. W. S., Griffin, D. A. & Shaw, G. (1985) Plant Physiol. 77, 635-641], was isolated from Phaseolus vulgaris embryos. Of all the potential pentose donors tested, UDP-xylose was the only substrate recognized by the enzyme. This indicates that the O-pentosyl derivatives previously obtained are O-xylosylzeatin and its ribonucleoside. The enzyme (UDP-xylose:zeatin O-xylosyltransferase, EC 2.4.2.-) has high affinity for trans-zeatin (K(m) 2 muM) and dihydrozeatin (K(m) 10 muM) but does not recognize cis-zeatin or ribosylzeatin. The molecular weight of the enzyme is approximately 50,000 and the pH optimum of the reaction is 8-8.5. Under comparable isolation and reaction conditions, similar enzyme activity could not be detected in P. lunatus embryos, confirming the genetic differences observed in vivo.

Journal Article↗
PubMed1987

Ubiquitin is detected in neurofibrillary tangles and senile plaque neurites of Alzheimer disease brains.

Neurofibrillary tangles (NFT) and neurites associated with senile plaques (SP) in Alzheimer disease-affected brain tissues were specifically immunostained with affinity-purified antibody preparations directed against ubiquitin. In addition, a class of neurites seen in brain regions containing NFT and SP were also specifically stained. Cross-reactivity of the ubiquitin antisera for tau protein, neurofilament proteins, and high molecular weight microtubule-associated proteins (MAPs) were ruled out by (i) the inability of the ubiquitin antisera to stain these proteins in immunoblotting experiments and (ii) the inability of tau, neurofilament, and MAP preparations, when preincubated with the ubiquitin antisera, to inhibit the selective neurofibrillar staining observed. Our results are consistent with the suggestion that ubiquitin is covalently associated with the insoluble neurofibrillary material of NFT and SP. We propose that the ubiquitin-mediated degradative pathway may be ineffective in removing these fibrillar structures in Alzheimer disease brain.

Aged↗
PubMed1987

Vehicular transport safety for the child with disabilities.

This article reviews transport safety for the child with disabilities in vans, school buses, and automobiles. Because very little research has been done in this area, information about safety for children with disabilities has been extrapolated from information based on the nondisabled population. Commercially available car seats and harnesses, most of which are designed for the nondisabled child, can provide a high level of crash protection. Several available restraint systems are recommended.

Accidents, Traffic↗
PubMed1987

Spatial distribution of disease: three case studies.

Maps transformed so as to have constant density of residential population were used to analyze the spatial distribution of disease in three specific areas. Each area had received recent attention because of suspected environmental pollution. The area adjacent to the Rocky Flats Facility (CO) was examined to identify any association between possible plutonium releases and increases in lung cancer or leukemia incidence. The industrial area of northern Contra Costa County (CA) was studied to explore a relationship between petrochemical industrial emissions and histologic-specific lung cancers. Finally, a suspected increase in the risk of congenital cardiac defects possibly related to pollution of the Santa Clara County (CA) water supply was investigated. No evidence of elevated risk of disease was found to be associated with either the Rocky Flats Facility or the polluted water of Santa Clara County. An increase in lung cancer, found by other investigators in earlier years, was shown to persist in association with industrial emissions in Contra Costa County.

Adult↗
PubMed1987

Assessment of potential acute health effects in agricultural workers exposed during the application of chlordimeform.

Agricultural workers exposed to chlordimeform (Cdf) used as a pesticide on cotton in Imperial County, California, were monitored during the 1982 application season. Cdf metabolites were found in the urine of 132 workers and were positively correlated with the length of exposure and nature of job activity. Persons mixing and loading and engaged in miscellaneous tasks such as cleaning and maintenance of equipment had the greatest exposure. There was no evidence of urinary tract irritation by microscopic analysis of the urine, nor were significant differences found between preseason and postseason serum chemistry results. Despite the use of protective clothing and closed system transfer devices, Cdf was absorbed by workers as evidenced by urinary metabolite excretion.

Agricultural Workers' Diseases↗
PubMed1986

A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation.

The mRNAs of transiently expressed genes frequently contain an AU-rich sequence in the 3' untranslated region. We introduced a 51 nucleotide AT sequence from a human lymphokine gene, GM-CSF, into the 3' untranslated region of the rabbit beta-globin gene. Our experiments demonstrate that this caused the otherwise stable beta-globin mRNA to become highly unstable in vivo. The instability conferred by the AU sequence in the mRNA was partially alleviated by treatment of the cells with cycloheximide. We propose that the AU sequences are the recognition signal for an mRNA processing pathway which specifically degrades the mRNAs for certain lymphokines, cytokines, and proto-oncogenes.

Base Sequence↗