Search PubMed⌕ Search

Biomedical subjects

J Ho

Publications and source records attributed to J Ho.

At least 73 records · Page 4Linked to original sources

A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis.

Mouse embryos lacking the receptor tyrosine kinase, Flk1, die without mature endothelial and hematopoietic cells. To investigate the role of Flk1 during vasculogenesis and hematopoiesis, we examined the developmental potential of Flk1-/- embryonic stem cells in chimeras. We show that Flk1 is required cell autonomously for endothelial development. Furthermore, Flk1-/- cells do not contribute to primitive hematopoiesis in chimeric yolk sacs or definitive hematopoiesis in adult chimeras and chimeric fetal livers. We also demonstrate that cells lacking Flk1 are unable to reach the correct location to form blood islands, suggesting that Flk1 is involved in the movement of cells from the posterior primitive streak to the yolk sac and, possibly, to the intraembryonic sites of early hematopoiesis.

Amnion↗

The nuclear receptor homologue Ftz-F1 and the homeodomain protein Ftz are mutually dependent cofactors.

Nuclear hormone receptors and homeodomain proteins are two classes of transcription factor that regulate major developmental processes. Both depend on interactions with other proteins for specificity and activity. The Drosophila gene fushi tarazu (ftz), which encodes a homeodomain protein (Ftz), is required zygotically for the formation of alternate segments in the developing embryo. Here we show that the orphan nuclear receptor alphaFtz-F1 (ref. 3), which is deposited in the egg during oogenesis, is an obligatory cofactor for Ftz. The two proteins interact specifically and directly, both in vitro and in vivo, through a conserved domain in the Ftz polypeptide. This interaction suggests that other nuclear receptor/homeodomain protein interactions maybe important and common in developing organisms.

Alleles↗

Design of an instrument for real-time detection of bioaerosols using simultaneous measurement of particle aerodynamic size and intrinsic fluorescence.

A prototype instrument has been constructed to measure individual airborne particles based on their aerodynamic size and their intrinsic fluorescence at selected excitation and emission wavelength bands. The instrument combines features of an aerodynamic particle sizing device with capabilities similar to those of a liquid flow cytometer. The goal of the instrument is to provide real-time data indicative of particle characteristics, and it is especially targeted to respond to bioaerosols from 0.5 to 10 micrometers (aerodynamic diameter) with intrinsic fluorescence exited at a wavelength of 325 nm and emitting from 420 to 580 nm. This size range covers individual airborne bacteria and bacteria clusters, and the fluorescence sensitivity is selected for biological molecules commonly found in cellular systems, for example, reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H] and riboflavin. Initial tests with nebulised Bacillus subtilis var. niger (BG, ATCC 9372) spores have shown that, for both individual spores and spore clumps, a low level of fluorescence is detected from 17% of the particles. This detection percentage is on the same order as previous experiments that have measured viability of about 12% for mechanically dispersed BG spores (Ho and Fisher (1993) Defense Research Establishment Suffield Memorandum 1421) and suggests a need for further investigation into the possible relationship between the detected fluorescence and viability of bacterial spores.

Aerosols↗

Parental involvement in diabetes management tasks: relationships to blood glucose monitoring adherence and metabolic control in young adolescents with insulin-dependent diabetes mellitus.

OBJECTIVES: The goal of this study was to identify parental behaviors that relate to adherence and metabolic control in a population of young adolescents with insulin-dependent diabetes mellitus (IDDM), and to understand the interrelationships among the variables of parental involvement, adherence to blood glucose monitoring, and glycemic control. STUDY DESIGN: A cross-sectional design was used to investigate parental involvement in diabetes regimen tasks in 89 youth, aged 10 to 15 years, with IDDM. Levels of parental involvement in blood glucose monitoring (BGM) and insulin administration were evaluated through interviews. Assessment of adherence was made by physicians or nurses, independent of patient or parent reports of adherence. Glycemic control was assessed with glycosylated hemoglobin (HbA1c) (reference range, 4% to 6%). RESULTS: There were significant differences in the mean HbA1c values between the older (13 to 15 years of age) (HbA1c = 8.9% +/- 1.03%) and younger (10 to 12 years) patients (HbA1c = 8.4% +/- 1.06%) (p < 0.02). Parental involvement in BGM was significantly related to adherence to BGM (number of blood sugar concentrations checked daily) in both groups of adolescent patients. The younger patients monitored their blood glucose levels more frequently than did the older patients, 39% of the younger patients checked sugar concentrations four or more times daily compared with only 10% of the older group (p < 0.007). In a multivariate model controlling for age, gender, Tanner staging, and duration of diabetes, the frequency of BGM was a significant predictor of glycemic control (R2 = 0.19, p < 0.02). Increased frequency of BGM was associated with lower HbA1c levels. When the frequency of BGM was zero or once a day, the mean HbA1c level was 9.9% +/- 0.44 (SE); when the frequency of BGM was two or three times a day, the mean HbA1c level was 8.7% +/- 0.17; and when the frequency of BGM was four or more times daily, the mean HbA1c level was 8.3% +/- 0.22. CONCLUSIONS: Parental involvement in BGM supports more frequent BGM in 10- to 15-year-old patients with IDDM. This increased adherence to BGM is associated with better metabolic control (i.e., lower HbA1c levels). These findings suggest that encouraging parental involvement in BGM with 10- to 15-year-old patients with IDDM may help to prevent the well-documented deterioration in glycemic control and adherence to treatment that often occurs in later adolescence.

Adolescent↗

Micromachined analytical devices: microchips for semen testing.

Micromachined devices (microchips) have been designed and tested for a range of clinically important assays. In this study we compare sperm motility determined using disposable glass microchips and a conventional Makler chamber. The 17 x 14 mm glass microchips contained three etched test structures each comprising either duplicate or quadruplicate analytical microchannels. Semen samples with sperm counts ranging from 21 to 78 million sperm per ml and forward progression scores of from 1+ to 3+ were evaluated and swimming times ranging from 360 s (3.3+ progression) to 770 s (1+,2 forward progression) observed in the microchips. Motility determined by the time taken for sperm to swim to the end of a microchannel (100 microns wide x 40 microns deep x 10 mm long) in the microchip correlated with forward progression of the sperm determined by the conventional Makler chamber method. This study demonstrates the feasibility of microchips for sperm motility testing and suggests that this technique would be applicable to the study of other types of motile cells.

Biotechnology↗

Mobilization of predominantly Philadelphia chromosome-negative blood progenitors using cyclophosphamide and rHUG-CSF in early chronic-phase chronic myeloid leukaemia: correlation with Sokal prognostic index and haematological control.

Mobilization of Philadelphia chromosome (Ph) negative blood progenitors was attempted in 23 newly diagnosed chronic myeloid leukaemia (CML) patients using a regimen of cyclophosphamide (CY) 5 g/m2 and rHUG-CSF 150 microg/m2 daily. This regimen was well tolerated with no major adverse events reported. More than 2 x 10(6)/kg CD34+ cells were collected in 21 patients (91%). Predominantly Ph-negative mobilization (0-25% Ph-positive) was seen in 30% of cases overall and was confined to patients with a Sokal prognostic score < 1 (7/11 with Sokal score <1; 0/12 with Sokal score > or = 1). Within the low Sokal index group, a low WBC count pre-mobilization and a low WBC nadir both correlated strongly with Ph-negative mobilization (P = 0.006 and 0.02 respectively). Five of 19 patients receiving at least 6 months of Roferon A therapy post mobilization achieved a major cytogenetic response; all five patients were Ph-negative mobilizers. Therefore CML patients can be divided into a good-prognosis group in whom predominantly Ph-negative progenitors can be mobilized using a regimen of moderate intensity if haematological control is achieved pre-mobilization, and a poor-prognosis group for whom predominantly Ph-positive cells are mobilized with this regimen regardless of haematological control.

Adult↗

Movement and subcellular localization of a tobamovirus in Arabidopsis.

Tobamoviruses represent a well-characterized system used to examine viral infection, whereas Arabidopsis is a choice plant for most genetic experiments. It would be useful to combine both approaches into one experimental system for virus-plant interaction. Most tobamoviruses, however, are not pathogenic in Arabidopsis. Here, we describe infection of Arabidopsis by a recently discovered crucifer-infecting turnip vein clearing tobamovirus (TVCV). Using this system, we determined patterns and kinetics of viral local and systemic movement within Arabidopsis plants. Localization studies showed that the virus infects both vegetative and reproductive plant tissues. However, there may be a transport barrier between the seed coat and the embryo which virions cannot cross, preventing seed transmission of TVCV. The ability to move both locally and systemically in Arabidopsis, causing mild and fast-developing symptoms but allowing survival and fertility of the infected plants, distinguish TVCV infection of Arabidopsis as a model system to study virus-plant interaction.

Arabidopsis↗

Clinicopathologic studies of thymic carcinoids in multiple endocrine neoplasia type 1.

Thymic carcinoid is part of the multiple endocrine neoplasia type 1 (MEN1) syndrome occurring predominantly in male patients who were heavy smokers, presenting most commonly in middle age. In contrast with metastatic midgut carcinoids, MEN1-related thymic carcinoid is not associated with carcinoid syndrome, nor is it associated with Cushing syndrome, in contrast with sporadic thymic carcinoids. Local invasion and metastasis are common. Prognosis is poor because of late detection, lack of effective treatment, and the aggressive nature of the tumor. All patients with thymic carcinoids should be investigated for MEN1, including thorough clinical evaluation and family studies. Anterior mediastinal lesions in MEN1 male patients should be considered thymic carcinoids until proven otherwise. All male MEN1 patients and asymptomatic gene carriers should be warned of the risk of thymic carcinoids and the possible link to smoking. Computed tomography (CT) of the chest is recommended on first screening for MEN1 in male patients more than 25 years of age, followed by yearly chest X-rays and chest CT every 3 years. Prophylactic thymectomy should be carried out during subtotal or total parathyroidectomy on MEN1 patients.

Adult↗

Can misoprostol and omeprazole reduce nicotine and ethanol induced gastric mucosal injury? A quantitative macroscopic and microscopic analysis in rats.

We compared the effects of misoprostol, omeprazole and methylcellulose (control) on gastric mucosal injury induced by nicotine and/or ethanol. The results demonstrate that misoprostol and omeprazole each significantly reduce macroscopic injury and deep injury at a microscopic level (P < 0.05) induced by nicotine alone, ethanol alone or a combination of ethanol and nicotine. Misoprostol and omeprazole each reduced the leakage of fluorescein isothiocyanate-albumin into the interstitium in the gastric mucosa. Misoprostol and omeprazole are each effective in preventing injury induced by nicotine and ethanol and vascular factors are involved.

Animals↗

Putative kappa-2 opioid agonists are antihyperalgesic in a rat model of inflammation.

It has been demonstrated that kappa-2 opioid receptor agonists can inhibit the current that flows through the N-methyl-o-aspartate (NMDA) subclass of excitatory amino acid receptor. NMDA receptor antagonists have been shown to be effective antihyperalgesic agents when administered intrathecally into rats. Antihyperalgesia is defined as the ability to block enhanced sensitivity, usually produced by nerve injury or inflammation, to nociceptive stimuli. Thus, the hypothesis was proposed that kappa-2 opioid receptor agonists would be antihyperalgesic when injected intrathecally into rats with an inflamed hind paw. The kappa agonists bremazocine and GR89,696 were effective at reversing the hyperalgesia associated with the inflamed hind paw but did not influence the sensitivity of the noninflamed hind paw to noxious heat. The kappa-1-selective agonist U69,593 had no effect on the heat sensitivity of either the inflamed paw or the noninflamed paw. Intrathecal injection of the mu-selective agonist [D-Ala2,N-MePhe4,Gly5-ol]enkephalin or the delta-selective agonist [D-Pen(2,5)]enkephalin elevated paw withdrawal latencies to heat in both hind paws. These findings indicate that activation of presumed kappa-2 receptors in the rat spinal cord results in suppression of the hyperalgesic state without influencing normal sensitivity to noxious stimuli. It is proposed that the antihyperalgesic effect of kappa-2 receptor activation is mediated by the ability of the opioid receptor to reduce the flow of current through the NMDA receptor ionophore.

Analgesics↗

Changes in hepatic portal resistance and in liver morphology during regeneration: in vitro study in rats.

OBJECTIVE: To study the effects of liver regeneration on hepatic portal resistance and on the morphology of liver sinusoids. DESIGN: Experimental in vitro study. SETTING: University laboratory, Hong Kong. ANIMALS: 10 Groups of 6 male Sprague Dawley rats each. INTERVENTIONS: Two thirds hepatectomy, with subsequent re-hepatectomy for measurements 0, 1, 3, 7, 21 and 56 days later. Perfusion of isolated livers and histomorphometry. MAIN OUTCOME MEASURES: Hepatic portal resistance and measurement of width and length of sinusoids. RESULTS: Liver weight was restored within 7 days of hepatectomy. Hepatic portal resistance/g of liver increased, reaching a maximum at 3 and 7 days of hepatectomy, and subsequently returned to initial values after 56 days. Width of sinusoids decreased to a minimum within 3 to 7 days of hepatectomy, and subsequently returned close to initial values within 56 days of hepatectomy. The changes in hepatic portal resistance occurred in phase with the changes in the width of liver sinusoids. CONCLUSIONS: There is a transient increase in hepatic portal resistance/g of liver during regeneration; transient narrowing of sinusoids may contribute to this change.

Animals↗

Pathogenesis of gastric lymphoma: the enigma in Hong Kong.

BACKGROUND: Helicobacter pylori (H. pylori) infection has been postulated to be a pathogenetic factor in gastric lymphoma. However, the etiological factors for gastric lymphoma could vary in different populations. MATERIALS AND METHODS: We looked for histological evidence of H. pylori infection in 53 gastrectomy specimens from Hong Kong Chinese patients with primary gastric B-lymphoma. We also screened for Epstein-Barr virus (EBV) in these cases using in situ hybridization with oligonucleotide probes for EBV-encoded small RNA1 and 2. RESULTS: H. pylori was found in 29 of 53 (55%), including 8 of 13 (62%) cases of low-grade lymphoma of mucosa-associated lymphoid tissue (MALT) type. These infection rates in gastric lymphoma are lower than those reported in Western populations (80%-100%) and comparable to that found in healthy Chinese blood donors (55%) or in non-ulcer dyspeptic patients (52%-57%). EBV was found in tumor cells only in one case of high-grade gastric lymphoma with low-grade MALT component which was H. pylori-negative, and in occasional nontumor-lymphoid cells in 7 other cases. CONCLUSIONS: These results suggest that (1) the role of H. pylori in pathogenesis of gastric lymphoma may vary in different populations; (2) very few gastric lymphomas are associated with EBV; (3) not all low-grade gastric MALT lymphomas are H. pylori-dependent.

Adult↗

Gastric cancers in Singapore: poor prognosis arising from late presentation.

BACKGROUND: Mortality rates from gastric cancer, apart from those derived from Japanese series, remain poor. This paper sought to determine the present outcome of gastric carcinoma in a predominantly Chinese population in Singapore. Prognostic factors useful in predicting survival were also evaluated in this population. METHOD: All cases of histologically confirmed gastric adenocarcinoma presenting in 1992 were entered into a prospective database. Prognostic factors related to age, sex, site of disease, depth of invasion, histological grade, nodal status and stage of disease were evaluated in patients with resectable disease to determine their utility in predicting survival. RESULTS: Of 131 consecutive patients with histologically proven adenocarcinomas, 37% had distant metastases at presentation predominantly in the liver (21%) and peritoneal cavity (20%). Sixty-four per cent of patients underwent surgery and in only 51% of these patients was resection of the tumour possible. Stages III and IV (T4N2) locally advanced disease were present in 38% of patients. Thus the majority of patients presented with late or metastatic disease (75%, stages III and IV). Sixty per cent of patients were alive at 1 year and 40% at 2 years after resection of the tumour (Kaplan-Meier survival plots). In contrast, no patient survived longer than a year if the tumour was not resectable (P < 0.001, log-rank test). Median survival of patients without surgery was 12 weeks. Median survival for patients with resected stage IV disease was 23 weeks, compared to 18 weeks after surgical bypass. Age, sex, site, depth of invasion and histological grade did not significantly predict survival. Patients with node-negative disease survived longer (2 years. 70%) than those with nodal involvement (2 years, 44%: P = 0.06, log-rank test). Pathologic staging with the TNM system was useful in predicting survival (P < 0.001). Sixty per cent of patients with stage I and II disease were alive at 2 years compared to 54% with stage III disease and 0% with stage IV disease. CONCLUSION: The prognosis of stomach cancer remains poor, due predominantly to late presentation. Pathologic TNM staging and nodal status were useful in predicting survival outcome after resection. If the tumour were resectable, survival was appreciable even in patients with advanced stage III (2 years. 54%) and stage IV (1 year, 40%) disease. Strategies to improve outcome should focus on early detection of gastric carcinomas.

Adult↗

An incremental response to high-dose therapy in multiple myeloma.

Results of conventional chemotherapy for multiple myeloma are disappointing. High-dose chemoradiotherapy with auto-transplantation is increasingly reported and some results are encouraging. We report the results of peripheral blood stem cell transplantation (PBSCT) for multiple myeloma at a single institution over a 6-year period. Forty patients, including 18 de novo patients, received debulking chemotherapy consisting of vincristine, adriamycin, and dexamethasone or methyl-prednisolone followed by stem cell mobilization with high-dose cyclophosphamide. Twenty-nine patients received PBSCT following high-dose chemoradiotherapy. Following PBSCT 92% of evaluable patients obtained at least a partial remission and 29% reached complete remission. Objective treatment responses, defined as at least a 50% reduction in serum paraprotein or marrow plasma cells, were observed following each treatment step of debulking chemotherapy, mobilization and PBSCT in 50, 42 and 71% of patients, respectively. The median overall survival from diagnosis in patients transplanted was 50 months and the median overall and progression-free survivals following transplant were 26 and 18 months, respectively. Median follow-up was 28 months. Overall treatment-related mortality was 20% but was significantly lower in de novo vs previously treated patients at 6 and 33% respectively (P = 0.027). De novo patients were more likely to obtain complete remission and had a longer overall survival following transplant but overall survival from diagnosis was similar to previously treated patients. A low serum B2M before mobilization predicted a longer progression-free survival. PBSCT needs to be considered early following diagnosis to maximise treatment response and reduce the high treatment-related mortality seen in heavily pretreated patients. In this treatment program a dose response effect in multiple myeloma was observed possibly suggesting that more intensive therapy than a single transplant may effect greater disease response.

Adult↗

Hepatic manifestation of malignant histiocytosis: a case study.

Malignant histiocytosis, as defined by Rappaport, is now known as a manifestation of malignant lymphoma, the majority of which is the T-cell type. However, unlike the typical presentation of most non-Hodgkin lymphomas, this condition presents with atypical features mimicking acute hepatitis or infectious mononucleosis. The latter diagnosis is often made because of the occurrence of atypical mononuclear cells on the peripheral blood films. This is clearly seen in the seven patients we report where the initial diagnoses were that of viral fever or hepatitis. Some characteristics were found in these patients to differentiate the condition from infectious mononucleosis (IMS) and acute hepatitis (AH): paucity of lymph nodes, cholestasis and prolonged prothrombin time (PT) which is atypical IMS; persistent fever, thrombocytopaenia and disproportionately high aspartate aminotransferase which is unusual in AH in the absence of any drug or alcohol history. The PT is the most important prognosis factor. Early diagnosis and treatment led to improved survival in an otherwise aggressive and rapidly fatal condition.

Acute Disease↗

Sudden death from ruptured septic myocardial infarct in an intravenous drug addict.

A case of ruptured septic myocardial infarct with death from cardiac tamponade in an intravenous drug addict with left-sided infective endocarditis and septic coronary artery embolism is described. To the best of our knowledge, there is no previous report of such a case in the literature. Although uncommon, infective endocarditis with coronary embolisation is a well-documented cause of myocardial infarction, although not normally associated with ventricular free wall rupture, and should be considered in intravenous drug addicts who present with cardiac symptoms and signs of sepsis.

Coronary Thrombosis↗