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Biomedical subjects

M Y Ho

Publications and source records attributed to M Y Ho.

At least 55 records · Page 3Linked to original sources

Oxytocin transgenic mice.

We have compared the expression patterns in transgenic mice of bovine oxytocin constructs consisting of the 0.9 kilobase pair (kbp) structural gene flanked by varying lengths of upstream and downstream sequences. Over 200 offspring were derived from fertilized one-cell mouse eggs injected with construct bOT6.5, which consists of 3 kbp of upstream sequences and 2.6 kbp of downstream sequences. However, no transgenic founders were identified. In parallel experiments with other constructs, 30% of pups carried integrated copies of the injected transgene DNA. It therefore appears that bOT6.5 is toxic to mouse embryos. As previously reported (Ang et al., 1991), bOT, consisting of 2.6 kbp of downstream sequences and 0.6 kbp of upstream sequences, was expressed in lung and in testicular Sertoli cells, but no expression was detected in the hypothalamus. bOT3.5, which consists of 0.6 kbp of upstream sequences and 1.9 kbp of downstream sequences, retains testis and lung expression, but, surprisingly, is also expressed in the hypothalamus. These data suggest that the 0.7 kbp of downstream sequences that are present in bOT, but which are absent from bOT3.5, contain elements that mediate the repression of hypothalamic expression. The activity of this repressor must be itself overcome in the normal genomic context of the bovine OT gene. Within the hypothalamus, in situ hybridisation analysis has revealed expression of bOT3.5 in the supraoptic nucleus (SON) and paraventricular nucleus (PVN), but not in the suprachiasmatic nucleus (SCN). In parallel with the response of the endogenous murine OT RNA, 7 days of salt-loading resulted in a significant increase in the level of transgene RNA in the SON. In the PVN, neither the endogenous OT RNA nor the transgene RNA responded significantly to salt-loading. Transgene RNA levels in the hypothalamus have also been shown to be elevated during late pregnancy and lactation.

Animals↗

Ectopic vasopressin expression in MMTV-Wnt-1 transgenic mice modifies mammary tumor differentiation and pathology.

A transgenic mouse model has been developed to test the involvement of ectopic neuropeptide production as a secondary factor in cancer. Mice bearing a mouse mammary tumor virus-vasopressin (MMTV-VP) fusion transgene synthesized authentic vasopressin in mammary ducts and alveoli, but this had no effect on mammary gland development and growth. Mice bearing the MMTV-VP transgene were then mated with mice bearing the MMTV-Wnt-1 transgene to produce bitransgenic animals. Two types of mammary tumor develop in MMTV-Wnt-1 mice; type A mammary adenocarcinomas are uniform with fine acinar structure composed of small epithelial cells arranged to form round cavities and elongated tubules, while adenocarcinoma type B tumors have acinar areas, cystic spaces filled with blood or fluid, intracystic papillary projections, and cords as well as sheets of cells. Compared to the MMTV-Wnt-1 mice, the bitransgenic animals developed proportionally less type B tumors. Further, type B mammary adenocarcinomas from bitransgenic mice exhibited increased proliferation and growth, as judged by mitotic index and argyrophilic nucleolar organizer region counts, compared to type B tumors from MMTV-Wnt-1 mice. These data provide evidence that ectopic neuropeptide production can modulate the development of tumors in vivo.

Adenocarcinoma↗

Facilitated acquisition of a temporal discrimination following destruction of the ascending 5-hydroxytryptaminergic pathways.

This experiment examined the effect of destroying the 5-hydroxytryptaminergic (5HTergic) pathways on the acquisition and performance of discrimination between two brief time intervals. Rats that had received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei, and sham-lesioned control rats were trained in a series of discrete trials to press lever A following a 200-ms presentation of a light stimulus and lever B following an 800-ms presentation of the same stimulus. Both groups gradually acquired accurate performance, attaining 80%-85% accuracy by the end of 40 sessions. The lesioned group learnt the task significantly faster than the control group. When stable performance had been attained, "probe" trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. The bisection point (duration corresponding to 50% choice of lever B) did not differ significantly between the two groups; however, the Weber fraction was significantly smaller in the lesioned group than in the control group. The levels of 5HT and 5-hydroxy-indole-acetic acid were markedly reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered. The results indicate that destruction of the 5HTergic pathways facilitates acquisition of a temporal discrimination. The lack of an effect of the lesion on the bisection point contrasts with our previous finding using longer stimulus durations; it is suggested that different behavioural processes may underlie millisecond-range and second-range temporal discrimination, and that these may be differently affected by 5HT depletion.

5,7-Dihydroxytryptamine↗

Effect of lesions of the ascending 5-hydroxytryptaminergic pathways on timing behaviour investigated with the fixed-interval peak procedure.

Twelve rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei; 12 rats received sham lesions. The rats were then trained for 60 sessions under a discrete-trials fixed-interval schedule (peak procedure). In half the trials, a reinforcer became available 40 s after trial onset, and the trial was terminated upon reinforcer delivery; the remaining trials were 120 s in duration, and reinforcement did not occur in these trials. Performance during the 120-s trials was characterized by increasing response rate during the first 40 s of the trial, declining response rate between 40 s and 80 s, and a secondary increase in response rate during the final 40 s of the trial. The lesioned group showed a broader "spread" of the response rate function than the control group (time between attainment of 70% of the peak response rate and subsequent decline of response rate below this level); however, the peak response rate and the time from trial onset until attainment of the peak response rate did not differ significantly between the groups; the spread/peak-time ratio was significantly greater in the lesioned group than in the control group. The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were markedly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected by the lesion. The results confirm the involvement of 5HTergic function in timing behaviour.

5,7-Dihydroxytryptamine↗

Direct high-performance liquid chromatographic separation of enantiomeric peptidoleukotriene antagonists.

Enantiomeric peptidoleukotriene antagonists, SK&F R-106203 and SK&F S-106203 can be effectively separated on a cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase. The utility of this chiral high-performance liquid chromatographic method in assigning absolute stereochemistry to SK&F S-106203-Z2, a non-crystalline amorphous compound which is not amenable to single crystal X-ray analysis, is demonstrated by correlation with the absolute configuration determined crystallographically for a second salt form.

Chromatography, High Pressure Liquid↗

Neuropeptide gene expression in transgenic animals.

Transgenic animal techniques offer today's neuroscientist the ability to experimentally manipulate neurosecretory systems with a precision undreamt of by our predecessors. The range of techniques now available, building as it does on our growing knowledge of physiological systems at the inter- and intercellular level, allows us to critically define molecular lesions and ask about their consequences to the whole organism. Neuroscientist should grasp the opportunities afforded by these recent developments.

Animals↗

Intracellular pH and catecholamine secretion from bovine adrenal chromaffin cells.

To study the role of intracellular pH (pHi) in catecholamine secretion and the regulation of pHi in bovine chromaffin cells, the pH-sensitive fluorescent indicator [2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein] was used to monitor the on-line changes in pHi. The pHi of chromaffin cells at resting state is approximately 7.2. The pHi was manipulated first by incubation of the cells with NH4+, and then the solution was replaced with a NH4(+)-free solution to induce acidification of the cytoplasm. The pHi returned toward the basal pH value after acidification within 5-10 min in the presence of Na+ or Li+, but the pHi stayed acidic when Na(+)-free buffers were used or in the presence of amiloride and its analogues. These results suggest that the pH recovery process after an acid load is due to the Na+/H+ exchange activity in the plasma membrane of the chromaffin cells. The catecholamine secretion evoked by carbachol and Na+ removal was enhanced after the cytoplasm had been made more acidic. It appears that acidic pH favors the occurrence of exocytosis.

Adrenal Medulla↗

Malignant mesothelioma in infancy.

Malignant mesothelioma in infancy has rarely been reported in the literature. A 19-month-old female infant with massive malignant epithelial mesothelioma of the pleura underwent postmortem examination. Histochemical study confirmed the diagnosis by revealing acid mucosubstance in the tumor, which was removed by hyaluronidase. The tumor cell had clear cytoplasm that was positive for periodic acid-Schiff staining, which could be totally abolished by diastase. This correlated well with the electron microscopic finding that there had been massive accumulation of glycogen in the cytoplasm. There was no information about environmental exposure to asbestos.

Adenocarcinoma↗

Diagnosis of enteric fever by inhibition assay using peroxidase-labelled monoclonal antibody and Salmonella typhi lipopolysaccharide.

An enzyme-linked immunoassay was developed for diagnosing enteric fever. The test measured the inhibition of binding between a labelled, monoclonal IgM antibody and the insolubilized antigen, Salmonella typhi lipopolysaccharide (LPS). Good discrimination was seen between 32 proven typhoid cases (88.0 +/- 4.4% inhibition) and non-typhoid cases. The latter consisted of 27 febrile patients bacteriologically and serologically (Widal test) found to be negative for typhoid (26.3 +/- 10.8% inhibition), 46 patients screened for syphilis (VDRL test) but found negative (31.2 +/- 13.3% inhibition), and 27 healthy blood donors (44.6 +/- 13.9% inhibition). The test also efficiently detected all 5 known typhoid carriers (90.6 +/- 3.4% inhibition). The antibody binds antigen 9 in the LPS; however, this reaction was inhibited by antibodies directed against both this antigen and an adjacent antigen, 12. Anti-12 antibodies presumably inhibit by steric hindrance and their importance in the test is discussed. Thus, the assay potentially detects (only) those systemic infections caused by salmonellae that possess antigen 9 or 12 (viz. S. typhi and S. paratyphi A).

Adult↗

Group B Streptococcal infection in neonates: an 11-year review.

Group B Streptococcal (GBS) infection is an important cause of infant morbidity and mortality. The purpose of this study is to evaluate the incidence, clinical characteristics, mortality and complications of this infection. From 1985 through 1995, 66 infants with early onset disease (EOD) and 23 infants with late onset disease (LOD) were treated at Mackay Memorial Hospital (MMH). The occurrence rate of EOD was 3.26-10.08/1000 admissions. The incidence of the disease was 0.11-1.39/1000 live births. Of the 66 EOD infants, 24 (36%) were preterm infants. There were 33 (50%) infants in EOD category with respiratory distress and 40 (60%) infants with sepsis. Among the 23 LOD infants, 3 (13%) were preterm infants. There were 6 (13%) infants in LOD category with respiratory distress and 16 (69%) with sepsis. Nine (13%) EOD infants and 14 (60%) LOD infants had meningitis. Leukopenia occurred in 24 (36%) EOD infants and 5 (21%) LOD infants. Twelve (18%) EOD infants and 9 (39%) LOD infants had a history of prolonged rupture of membrane (PROM). The mortality rate was 14% in EOD and 4% in LOD infants. Four (17%) LOD infants developed neurological seguelae. Clinically, EOD infants were often premature and prone to develop sepsis, respiratory distress and leukopenia, while LOD often presented with meningitis and sepsis. Our estimated occurrence rate and incidence of EOD were similar to the European estimates. The influence of prenatal measures on EOD and the meaning of PROM on LOD need further evaluation.

Age of Onset↗

Liveborn trisomy 22: report of one case.

A case of trisomy 22 liveborn female baby with multiple congenital anomalies is described. Physical manifestations included failure to thrive, hypotonia, pre-auricular sinus, low set ears, hypertelorism, posterior low hair line, micrognathia, cleft palate, congenital heart disease, imperforated anus with anovulvar fistula, contracted pelvis and bilateral rocker-bottom feet. The infant died at two months of age. Cases of trisomy 22 usually present with many severe malformations, and they rarely survive to term. A review of the literature is presented to delineate this chromosome disorder.

Adult↗

[Complications in the use of mechanical ventilator in newborns: one year's experience].

A retrospective study was undertaken of 175 patients (119 males, 56 females) admitted to the neonatal intensive care unit of Mackay Memorial Hospital during the period of July 1, 1985 to June 30, 1986 who received mechanical ventilation during their stay at the hospital. Upon reviewing the clinical histories of these patients, the complication rate of mechanical ventilation was 31.9%. The percentages of each complication were: pneumothorax 50.0%, pneumomediastinum 5.2%, pulmonary interstitial emphysema 1.7%, atelectasia 13.8%, pneumonia 13.8%, chronic lung disease 13.8%, nasopharyngeal infection 1.7%. Survival rate of these ventilated patients with or without complication was not significant statistically (69.2% vs 65.6%). However, with regard to the hospital course, cases with complication had a significantly longer duration of ventilator usage, hospital stay and oxygen usage than uncomplicated cases. In conclusion, experienced personnel are needed to supervise the use of mechanical ventilation in neonates, and a team of well-trained nurses working in the neonatal intensive care unit are essential to minimize complications.

Chi-Square Distribution↗