Drug-induced stuttering treated with propranolol.
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Biomedical subjects
Publications and source records attributed to S Leong.
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Peripheral blood T-lymphocyte subsets in 179 Chinese subjects were enumerated by an indirect immunoalkaline staining method done on ordinary blood smears. Absolute counts (X 10(9)/L) were 1.32 +/- 0.53 (T11), 0.73 +/- 0.31 (T4), 0.45 +/- 0.22 (T8) for males (n = 135) and 1.22 +/- 0.39 (T11), 0.69 +/- 0.20 (T4), 0.44 +/- 0.19 (T8) for females (n = 44). T4:T8 ratio for males and females were 1.79 and 1.58, respectively (0.05 less than P less than 0.10). Within-film area-to-area difference was 4.2 +/- 2.1% (n = 537 films). Interobserver discrepancy was 54 per 3,000 cells counted, or 1.8%. Film-to-film difference was 5.4 +/- 2.6% (30 pairs). T-lymphocyte subsets enumeration by immunostaining blood smears is a simple and reliable alternative to the immunofluorescence method. It avoids procedures that could artifactually affect lymphocyte subsets. The lower T4:T8 ratios revealed in this study could result because of technical reasons.
We have used molecular hybridization techniques to show that hepatitis B virus (HBV) DNA from different individuals may have substantial differences in sequence homology. Seven specimens of HBV DNA were isolated from plasma of different blood donors. Samples were applied as dots to membranes and nick-translated to form probes. Densitometry of the radioautograms showed that hybridization was most extensive with probe prepared from the same specimen. The hybridization bias was statistically significant (P less than .02) and visible to the naked eye. Hybridization to probes that were digested with nuclease S1 before nick translation did not eliminate the bias. Nor was the bias related to the d/y subdeterminants; on the average, 15 other specimens hybridized equally well to probes prepared from HBV with the same or different subdeterminant. Many specimens among 37 other serum samples showed greater or lesser degrees of homology to different probes, as demonstrated by reprobing of samples fixed to nylon membranes.
The effects of interferon (IF) on erythropoietin (Ep) action and production were studied in mice. In comparison to control animals, Ep action in exhypoxic, polycythemic mice was significantly decreased (p less than 0.05) following two low dose injections of IF (2.9-3.5 X 10(4) units). In addition, renal Ep production in normal intact mice was also significantly decreased (p less than 0.01) following a single injection of IF (5.4-6.3 X 10(4) units) and hypoxic exposure.
Renal concentrating capacity following 18 hours of fluid deprivation was measured in 75 patients receiving prophylactic lithium therapy, and in 30 affectively ill subjects receiving other drugs. The lithium-treated patients had significantly lower urine osmolality and higher serum osmolality than the control subjects. Older subjects, patients maintained at higher serum lithium levels and those with a history of previous neurotoxicity showed the most impairment. Ten patients with urine osmolalities of less than 700 mOsm/1 following this test were investigated further. Inulin and para-amino hippurate (PAH) clearance rates were determined and the effect of a subpressor challenge of dopamine on these measures was observed. Half of the patients showed some reduction in inulin and PAH clearance, which was greatest in those patients who had been taking lithium for over 10 years. However, all of the patients tested showed the expected increase in renal blood flow and sodium and water excretion in response to dopamine. Six additional patients had clearance estimations made before starting lithium treatment which were repeated after a period of 3-6 months on the drug. No consistent changes in haemodynamics were observed. Lithium clearly reduces renal concentrating capacity, but other measures of renal tubular function were well preserved in patients receiving long-term therapy. Glomerular function may be slightly reduced in patients taking lithium for long periods. The results show that prophylactic lithium treatment does not affect renal cortical function adversely in the majority of patients, but impaired renal concentrating ability is a common accompaniment.
Three types of cleft lip were studied histologically before and during lip formation in mouse embryos. C57BL/6 embryos observed near term following treatment with 6-aminonicotinamide (6AN) at gestation D9/12 (vp day = day 0) had 18% median cleft lip. Treated embryos observed at D10 and D11 showed retarded somite and nasal placode development. Sections at lip closure time showed marked reduction of medial and some reduction of lateral nasal processes, and the mitotic index was significantly reduced in the nasal area on D10 and D11 but less consistently in the neural area. 6AN-treatment on D10/8, caused 22% lateral cleft lip. Treated embryos showed initial retardation of somite and nasal placode development that became normal by D11/14. Sections showed reduction of the medial and lateral nasal processes, and less organized denser nasal ectoderm. The mitotic index was significantly reduced in the nasal and neural areas on D10 and D11. In crosses having the major gene mutation dancer (Dc) 20% of embryos had lateral cleft lip and potential cleft lip mutant embryos showed reduced lateral and medial nasal processes. Mitotic index was not reduced in the nasal area but it was in the neural area. The CL/Fr strain, with a predisposing face shape in which 26% of the embryos have cleft lip of multifactorial origin, had a mitotic index similar to that of C57BL/6 (0% cleft lip) at lip closure time, D11/14, and prominent medial nasal processes. It is postulated that 6AN-induced median cleft lip is due to reduced cell proliferation in and size of the medial nasal processes; 6AN-induced lateral cleft lip to reduced cell proliferation and reduced medial and lateral nasal processes and dancer lateral cleft lip to reduction of the medial nasals.
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Fatty acid components of infant brain were determined to assess fatty acid requirements for synthesis of structural lipids in brain tissue during the last trimester of development in the fetus. Quantitative fatty acid analysis of cerebellum, frontal and occipital brain lobes indicated rapid accretion of chain elongation and desaturation products during the last trimester of brain growth. Frontal and occipital brain lobes were similar in fatty acid content. Fatty acid accretion rates were determined by regression analysis of tissue fat components at varying gestational ages. Tissue accretion of saturated and omega-9 fatty acids, as well as total fatty acid content, paralleled increases in whole brain weight. Levels of linoleic (C18:2, omega-6) and linolenic (C18:3, omega-3) acids were consistently low in brain during the last trimester of development, while marked substantial accretion of long chain desaturation products, arachidonic (C20:4, omega-6) and docosahexaenoic (C22:6, omega-3) acids occurred. Accretion of individual fatty acids of cerebellum also reflected changes in tissue total fatty acid content, with exception of the levels of C18:3, omega-3 and its chain elongation products present in cerebellum during the last trimester. These developmental changes and estimates of fatty acid incorporation into whole brain and cerebellum are quantitatively relevant to estimation of fatty acid requirements of the low birth weight neonate.
Total fatty acid content of infant brain was determined to assess minimal fatty acid requirements for synthesis of structural lipids in brain tissue during the first 13 weeks of life. Fatty acid accretion rates were determined by regression analysis of tissue fat components at varying postnatal ages. Quantitative fatty acid analysis indicated that postnatal accretion of long-chain polyenoic fatty acids in cerebellum, frontal and occipital brain lobes initially appeared to lag behind the rate of increase in brain weight and brain fat content. After a 4-week period total long-chain fatty acids increased at a rate similar to the increase in brain weight. Accretion of individual fatty acids in cerebellum also reflected changes in tissue total fatty acid content. These developmental changes in fatty acid components of whole brain and cerebellum are quantitatively relevant to estimation of the minimal extrauterine fatty acid requirements of the human neonate.
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The pattern of malformations in congenital anomalies such as Möbius syndrome and following prenatal cocaine exposure suggests that there is a zone of vascular vulnerability or ischemic sensitivity in the paramedian region of the developing brain stem. In the present study, postmortem examination of the brain of an infant with Möbius syndrome revealed mineralized foci concentrated in paramedian wedge-shaped areas of the pontine and medullary tegmentum. We also examined the development of brain stem vasculature in the rat at the light and ultrastructural level to determine whether anatomical features of the paramedian brain stem region could contribute to elevated incidence of vascular accidents in that zone. Several observations of relevance to the question of vascular vulnerability of the midline were made. Firstly, and as previously noted by other authors, the brain stem midline remains avascular for protracted periods during fetal life. We propose that the inability of vessels in the paramedian region to anastomose across the avascular midline gives rise to paramedian watershed zones that could be vulnerable to ischaemia in the event of hypoperfusion due to teratogenic action. Secondly, we studied the development of cytochrome oxidase activity in the fetal brain stem and noted high oxidative metabolic activity of the somatic efferent nuclei in the paramedian region, which could render their constituent neurons particularly susceptible to hypoxia. Thirdly, our ultrastructural examination revealed large amounts of extracellular space surrounding paramedian pontine vessels in comparison to laterally placed vessels, although there was no significant difference between the vessels of the two regions in tight junction length and endothelial thickness. We propose that the greater proportion of unoccupied extracellular space surrounding medial vessels may contribute to poorer support of these vessels in ischemic/reperfusion episodes. This poor support could in turn give rise to an increased risk of hemorrhage.
The smut fungi are obligately parasitic during the sexual phase of their life cycle, and the mating-type genes of these fungi play key roles in both sexual development and pathogenicity. Among species of smut fungi it is common to find a bipolar mating system in which one locus with two alternate alleles is believed to control cell fusion and establishment of the infectious cell type. Alternatively, several species have a tetrapolar mating system in which two different genetic loci, one of which has multiple alleles, control fusion and subsequent development of the infection hyphae. Cloned sequences from the a and b mating-type loci of the tetrapolar smut fungus Ustilago maydis were used as hybridization probes to DNAs from 23 different fungal strains, including smut fungi with both tetrapolar and bipolar mating systems. In general, all of the smut fungi hybridized with the mating-type genes from U. maydis, suggesting conservation of the sequences involved in mating interactions. A selection of DNAs from other ascomycete and basidiomycete fungi failed to hybridize with the U. maydis mating-type sequences. Exceptions to this finding include hybridization of DNA from the a1 idiomorph of U. maydis to DNA from one strain of U. violacea and hybridization of both a idiomorphs to DNA from Saccharomyces cerevisiae.