Search PubMed⌕ Search

Biomedical subjects

P Ho

Publications and source records attributed to P Ho.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of human follicular fluid on spermatozoa that have been cocultured with human oviductal cells.

OBJECTIVE: To investigate the sequential effects of human oviductal cells and human follicular fluid (hFF) on various sperm functions. DESIGN: Laboratory experimental study. SETTING: University gynecology unit. PATIENT(S): Fallopian tubes were from patients undergoing tubal ligation or hysterectomy. Semen was from men attending the subfertility clinics. INTERVENTION(S): Spermatozoa were treated with [1] 6 hours in Earle's balanced salt solution (EBSS-BSA; control); [2] 5 hours in EBSS-BSA and 1 hour with hFF (hFF); [3] 5 hours with oviductal cells and 1 hour in EBSS-BSA (coculture); and [4] 5 hours with oviductal cells and 1 hour with hFF (sequential). MAIN OUTCOME MEASURE(S): Motility, acrosome reaction, zona binding, and oocyte fusion. RESULT(S): Groups II and III spermatozoa had similar motility and were better than that of group I. Group IV displayed higher motility parameters than the other groups. Human follicular fluid induced acrosome reaction. The incidence of acrosome reaction in group IV was significantly lower than that in group II. Group III did not affect the acrosome reaction. Spermatozoa in groups II-IV had lower zona binding capacity than those in group I. Human follicular fluid stimulated oocyte penetration, whereas oviductal cells suppressed this effect of hFF. CONCLUSION(S): Oviductal cells maintained the fertilizing capacity of spermatozoa, whereas hFF facilitated the fertilization process of oviductal spermatozoa.

Acrosome Reaction↗
PubMed1999

A novel orthotopic model of breast cancer metastasis to bone.

Breast cancer affects approximately one woman in twelve and kills more women than any other cancer. If detected early, patients have a five year survival rate of 66%, but once metastatic disease has developed, there is no effective treatment. About 70% of patients with metastatic disease have bone involvement, while lungs and liver are the other common targets. Bone metastases cause severe pain, pathological fractures and hypercalcaemia and thus are a significant clinical problem. The development of new therapies for metastatic breast carcinoma depends on a better understanding of the mechanism of homing of the tumour cells to bone, liver and lungs and the factors required for their growth in these organs. Research on mechanisms of breast cancer metastasis, particularly to bone, has relied on in vitro studies or on tumour models in which the inoculation route is designed to promote delivery of tumour cells to a specific organ. Metastases in bone are achieved by inoculation into the right ventricle of the heart. To our knowledge there has been no report of a model of metastatic spread from the mammary gland to distant sites which reliably includes bone. In this paper, we describe our recent development of a novel murine model of metastatic breast carcinoma. The new model is unique in that the pattern of metastatic spread closely resembles that observed in human breast cancer. In particular, these murine breast tumours metastasise to bone from the primary breast site and cause hypercalcaemia, characteristics not normally found in murine tumours, but common in human disease. Furthermore, in a preliminary characterisation of this model, we show that secretion of parathyroid hormone-related protein, a role for which has been implicated in breast cancer spread to bone, correlates with metastasis to bone. This model therefore provides an excellent experimental system in which to investigate the factors that control metastatic spread of breast cancer to specific sites, particularly bone. The special advantage of this system is that it involves the whole metastasis process, beginning from the primary site. Existing models consider mechanisms that pertain to growth of tumour once the site has been reached. An understanding of the regulation of these factors by potential therapeutic agents could lead to improvement in therapies designed to combat metastatic disease. For the first time, this development will allow exploration of the molecular basis of site-specific metastasis of breast cancer to bone in a clinically relevant model.

Animals↗
PubMed1999

Further clinical clarification of the muscle dysfunction in cervical headache.

The Headache Classification Committee of the International Headache Society listed impairments in cervical muscle function as criteria for headaches of cervical spine origin. Fifteen subjects with cervical headache and 15 controls were tested for the frequency of abnormal responses to passive stretching and abnormal muscle contraction. A new test of cranio-cervical flexion was used to assess the contraction of the deep neck flexors. Results indicated a trend towards a higher frequency of abnormal response to passive stretching of the muscles examined in the cervical headache group but only the upper trapezius proved significantly different to the control group. Deep neck flexor muscle contraction was significantly inferior in the cervical headache group. From the perspective of physical characterization of cervical headache, it appears that response from passive stretch of muscle may not be a strong criterion for cervical headache but deep neck flexor performance may have potential to identify musculoskeletal involvement in headache. The finding may also provide positive directions for conservative treatment of cervical headache.

Adult↗
PubMed1998

LPS-induced TNF-alpha release from and apoptosis in rat cardiomyocytes: obligatory role for CD14 in mediating the LPS response.

The bacterial endotoxin lipopolysaccharide (LPS) contributes to the cardiovascular collapse and death observed in patients with sepsis. Because LPS has such profound effects on cardiac performance, we speculate that direct effects of LPS could be demonstrated on cardiomyocytes in culture, and that these direct effects are mediated by the LPS receptor, CD14. Accordingly, in this study, we provide evidence for CD14-dependent cardiotoxic effects of LPS including the LPS-stimulated secretion of tumor necrosis factor alpha (TNF-alpha) from cardiomyocytes. TNF-alpha is an inflammatory cytokine which is known for its negative inotropic effects on cardiac performance, but has not until recently been shown to be produced by cardiac cells. In this study, LPS was found to stimulate strongly in a dose-dependent manner the secretion of TNF-alpha from cultured adult rat cardiomyocytes. Further, LPS-induced TNF-alpha secretion was blocked by an inhibitor of TNF-alpha processing, metallomatrix protease inhibitor (TAPI). Molecular and immunological evidence demonstrated the presence of LPS receptors (CD14) on cardiomyocytes. Attenuated TNF-alpha secretion following PI-PLC treatment confirmed the functional importance of CD14 for LPS-mediated myocardial effects. Importantly, LPS also triggered apoptosis in cultured cardiomyocytes as quantified by single-cell gel electrophoresis of nuclei exhibiting DNA fragmentation patterns characteristic of apoptosis (i.e. cardiac comets). Apoptotic cell death was blocked by pre-incubation with the soluble TNF-alpha receptor fragment (TNFRII:Fc), suggesting that LPS-induced apoptosis was TNF-alpha-dependent and probably involved an autocrine function for the TNF-alpha whose secretion was under LPS control. The results of this study suggest that the cardiodepressant effects of LPS are dependent on CD14 signaling and may not only be due to acute negative inotropic effects of TNF-alpha but also may be complicated by TNF-alpha-induced apoptotic cell death which effectively reduces the number of working myocardial cells.

Animals↗
PubMed1998

Effect of modifying O2 diffusivity and delivery on glomerular and tubular function in hypoxic perfused kidney.

Is O2 diffusivity within renal capillaries rate limiting for O2 delivery to hypoxic renal tubules? Equations based on diffusion theory and developed here predict that soluble hemoglobin (Hb) increases O2 diffusivity by a factor of 1 + [442 Hb%/(P50 + PO2)], where P50 is the partial pressure of O2 at which the Hb is half saturated. To examine the effect of P50 and Hb concentrations on renal function, we perfused isolated rat kidneys with Hb-P35 (P50 = 35 mmHg) and Hb-P11 (P50 = 11 mmHg). Venous PO2 was lower with Hb-P11 (10 +/- 1 vs 16 +/- 1 mmHg with arterial PO2 = 35 mmHg and 28 +/- 2 vs. 40 +/- 2 mmHg with arterial PO2 = 140 mmHg; P < 0.001). Perfusate P50 did not influence vascular resistance, glomerular filtration rate, O2 consumption, Na reabsorption, protein excretion, or free water clearance. Percent glucose and phosphate excretion were lower with Hb-P11 than with Hb-P35 (P < 0.001). Urine glucose was 0.17 mmol/l with Hb-P11 and 0.77 mmol/l with Hb-P35 (P < 0.001). Hb-P35 (2%) doubled O2 delivery and lowered glucose and phosphate excretion to the level obtained with 1% Hb-P11. Thus Hb-P11 delivered O2 twice as effectively as Hb-P35 to high-affinity sodium glucose and phosphate cotransporters in the late proximal tubule (S3 segment). Hb-P11 may also have shunted O2 from the outer cortex to the outer medulla and facilitated O2 diffusion where PO2 was low. We conclude that diffusivity is a limiting factor in delivery of O2 to hypoxic tubules.

Animals↗
PubMed1998

Conduct of phase I trials in children with cancer.

PURPOSE AND METHODS: Future progress in the care of children with cancer requires appropriate evaluations of promising new agents for pediatric indications, beginning with well-conducted phase I trials. This report summarizes current guidelines for the conduct of pediatric phase I trials and represents a consensus between American and European investigators. The primary objective of pediatric phase I trials is to define safe and appropriate doses and schedules of new agents that can subsequently be used in phase II trials to test for activity against specific childhood malignancies. Prioritization of agents for evaluation in children is critical, since many more investigational agents are evaluated in adult patients than can be systematically evaluated in children. Considerations used in prioritizing agents include activity in xenograft models, novel mechanism of action, favorable drug-resistance profile, and activity observed in adult trials of the agent. RESULTS AND CONCLUSION: Distinctive characteristics of pediatric phase I trials, in comparison to adult phase I trials, include the necessity for multiinstitutional participation and their higher starting dose (typically 80% of the adult maximum-tolerated dose [MTD]), both of which reflect the relative unavailability of appropriate patients. The application of uniform eligibility criteria and standard definitions for MTD and dose-limiting toxicity (DLT) help to assure that pediatric phase I trials are safely conducted and reliably identify appropriate doses and schedules of agents for phase II evaluation. Where possible, pediatric phase I trials also define the pharmacokinetic behavior of new agents in children.

Antineoplastic Agents↗
PubMed1997

Sensitization to inhaled allergens as a risk factor for asthma and allergic diseases in Chinese population.

BACKGROUND: Allergen sensitization is associated with asthma and allergic disease in children, but such a relationship has not been confirmed in Chinese populations. OBJECTIVES: The objective of this study was to evaluate the effects of allergen sensitization and family history of atopy on asthma and allergic disease in Chinese schoolchildren from three southeast Asian populations. METHODS: Written questionnaires on respiratory and allergic symptoms were completed by parents of children of secondary-school age (age range 12 to 18 years) in Hong Kong (n = 1062), Kota Kinabalu in eastern Malaysia (n = 409), and San Bu in southern China (n = 737). A subsample of school-children underwent skin prick testing to common inhalant allergens (Hong Kong 471 children, Kota Kinabalu 321, San Bu 647). RESULTS: The prevalence of asthma and allergic disease in schoolchildren was highest in Hong Kong, intermediate in Kota Kinabalu, and lowest in San Bu. However, the overall rate of atopic sensitization was similar in the three populations (49% to 63%). House dust mite and cockroach were the two most common allergens causing sensitization and these gave rise to more than 95% of the positive skin test results in all three populations. By regression analysis, mite allergy was associated with rhinitis and asthma in all three populations, and a family history of asthma, rhinitis, or eczema was strongly associated with respective symptoms in the subjects. After adjusting for age, sex, atopic status, and family history of allergic disease, the place of residence remained a significant independent factor for asthma (odds ratio [OR] = 1.0 for Hong Kong, 0.57 for Kota Kinabalu, 0.15 for San Bu, p < 0.001), rhinitis (OR = 1.0 for Hong Kong, 0.59 for Kota Kinabalu, 0.15 for San Bu, p < 0.001), or eczema (OR = 1.0 for Hong Kong, 0.35 for Kota Kinabalu, 1.01 for San Bu, p < 0.001). CONCLUSION: Sensitization to indoor allergens was a significant risk factor for asthma and allergic disease, and familial clustering of disease was common in the region. However, the marked difference in disease prevalence in the three southeast Asian populations of Chinese schoolchildren cannot be explained by atopic sensitization and family history alone, and the place of residence was an independent risk factor for asthma and allergies, which suggests an important environmental role in disease pathogenesis.

Adolescent↗
PubMed1997

New drugs in non-Hodgkin's lymphoma.

While novel agents designed to target molecular abnormalities involved in lymphoma pathogenesis are most likely to improve current therapeutic results, cytotoxic therapy remains the main-stay of therapy. Several new chemotherapy agents, including purine antimetabolites, taxanes, camptothecins, suramin, and protein kinase C inhibitors, are discussed. Other issues important in lymphoma drug development, including the limited patient population available for evaluation of investigational agents, are also considered.

Adenosine↗
PubMed1996

Telomerase activity in hematopoietic cells is associated with self-renewal potential.

It has been proposed that the biological clock underlying the limited division potential of eukaryotic cells is telomere length. We assayed telomerase activity in single cells of the hematopoietic and immune systems. We examined hematopoietic stem cells at four stages of differentiation, lineage-committed progenitors, and mature myeloid and lymphoid cells. The frequency of telomerase-expressing cells within each population was proportional to the frequency of cells thought to have self-renewal potential. Among bone marrow hematopoietic stem cells, 70% exhibited detectable telomerase activity. The telomerase-expressing somatic cells observed in this study are not thought to be immortal, and expression was not correlated with cell cycle distribution or differentiation state. This study demonstrates that the developmental characteristic most consistently associated with telomerase expression is self-renewal potential.

Animals↗
PubMed1996

Pediatric phase I drug tolerance: a review and comparison of recent adult and pediatric phase I trials.

PURPOSE: We evaluated the ratio of pediatric to adult maximum tolerated doses (MTDs) from 70 Phase I studies conducted between 1975 and 1995. The aim of this study was to determine whether previously observed differences in drug tolerance between adult and pediatric Phase I patients have persisted over the 20-year period of this analysis. PATIENTS AND METHODS: Phase I trials of pediatric and adult patients with solid tumors as the predominant diagnosis and sharing similar dosing regimens were evaluated. For consistent comparison between Phase I studies, the MTD was defined as the drug dose one level below that yielding dose-limiting toxicity in >30% of patients. The ratio of pediatric to adult MTDs was calculated and plotted chronologically by year of pediatric study closure. Statistical evaluation of MTD ratios included regression and correlation analysis. The extent of therapy before Phase I study entry was also examined. RESULTS: Ninety-three Phase I studies were reviewed. Twenty-one drugs (70 studies) met our criteria for paired review of MTDs and analysis of the variation of ratio with time. The pediatric to adult MTD ratios ranged from 0.4 to 2.8, with a median of 1.2. Regression analysis of the ratio of MTD versus date of pediatric study closure supports a linear relationship of decreasing ratio with time (p<0.01). Analysis of the regression line predicts MTD ratios of 2.02 and 0.76 for 1974 and 1995, respectively. Of patients included in this analysis, 37.1% and 68.6% of adult and pediatric patients, respectively, were considered to have been heavily pretreated before study entry. A significant (p<0.001) downward trend with time was observed in the proportion of adult patients entering Phase I studies who had received both radiation and chemotherapy. CONCLUSIONS: The results of this review continue to show an equal or greater drug tolerance in the pediatric population when compared with adult patients for most drugs studied during Phase I trials. However, there appears to be significant trend of decreasing differences in drug tolerance between pediatric and adult Phase I patients with time, as defined by the descent of the MTD ratio toward values <1.0. Mechanisms to explain greater drug tolerance in children and the observation of decreasing maximum tolerated dose ratios with time are discussed. Limited data suggest that changes in degree of therapy before Phase I study entry may be influencing the MTD ratio.

Adult↗
PubMed1996

A rare case of multiple intussusceptions: intense segmentary lipomatosis of the ileum.

We report a patient who presented with intestinal obstruction; his small intestine showed intense segmentary lipomatosis associated with unusually situated multiple intussusceptions. Preoperatively, we diagnosed intussusceptions in the ileocecal region by ultrasonography and computed tomographic scan. During surgery, the ileum was dilated and contained numerous movable polypoid masses. One reducible intussusception was encountered in the ileocecal region. In addition, an ileoileal intussusception that could not be reduced was resected with an end-to-end anastomosis. At histological examination, more than 150 submucosal lipomas were found.

Adult↗
PubMed1995

Changing patterns of susceptibilities of blood, urinary and respiratory pathogens in Hong Kong.

The incidence and antimicrobial susceptibility of organisms isolated from blood, urine and respiratory specimens at a teaching hospital in Hong Kong were studied retrospectively from 1986-1993. The incidence of Gram-positive bacteraemia, particularly coagulase-negative staphylococci (CNS), increased significantly from 33.6 to 47.3% (P < 0.001) while that of Gram-negative bacteraemia fell from 60.0 to 47.0% (P < 0.001). Among blood isolates, methicillin resistance of CNS increased from 17.0 to 58.0% (P < 0.001) and cefuroxime resistance of Enterobacter spp. increased from 21.0 to over 50% (P < 0.01). Among urinary isolates, cefuroxime resistance of Klebsiella spp. (11.0 to 24.0%, P < 0.001) and Enterobacter spp. (32.0 to 75.0%, P < 0.001) increased. Nalidixic acid resistance among Gram-negative urinary isolates, except Proteus mirabilis, rose by three- to sixfold. For Streptococcus pneumoniae, isolated from the respiratory tract, penicillin resistance increased dramatically (2 to 18%, P < 0.001). For respiratory isolates of Haemophilus influenzae, ampicillin resistance increased from 17.0 to 29.0% (P < 0.001). These data are useful in guiding empirical treatment of nosocomial infections.

Bacteremia↗
PubMed1994

Asthma, allergy, and atopy in three south-east Asian populations.

BACKGROUND: Whilst many recent reports have suggested a rise in the prevalence of asthma and allergic disease in Western countries, little is known about the epidemiology of these common conditions in south-east Asia. This study compared the prevalence of asthma and allergic disease amongst secondary school students in three south-east Asian populations--Hong Kong, Kota Kinabalu in Malaysia, and San Bu in China--and investigated the associations with atopy and family history. METHODS: Secondary school students were given standard questionnaires on respiratory and allergic symptoms for completion by parents with response rates of 89.2% in Hong Kong (611 male, 451 female; mean (SD) age = 13.9 (1.8 years), 87.6% in Kota Kinabalu (134 male, 275 female; 15.5 (2.1) years), and 98.6% in San Bu (492 male, 245 female; 16.4 (1.8) years). Skin tests were performed in a subsample of students to determine atopic status. RESULTS: The respective prevalence (and 95% CI) for hayfever, eczema, and wheeze or asthma were 15.7% (13.5, 17.9), 20.1% (17.7, 22.5), 11.6% (9.3, 13.9) in Hong Kong, 11.2% (8.2, 14.3), 7.6% (5.0, 10.1), 8.2% (5.5, 10.9) in Kota Kinabalu, and 2.1% (1.2, 3.1), 7.2% (5.4, 9.1), 1.9% (0.7, 3.1) in San Bu. Atopy was common and was present in 49.0-63.9% of subjects in the three populations. Dust mite and cockroach were the commonest allergens that gave positive reactions in 42.8-60.5% and 25.7-35.9% of students respectively. A higher proportion of students in Hong Kong had severe degree of reactivity on skin test than the other two populations. Family history was associated with asthma and allergic symptoms in the three populations conferring a 3-80-fold increase in risk to family members and was a stronger predictor for asthma and allergy than atopy. CONCLUSIONS: Prevalence of asthma and allergic disease is low compared with Western countries, but considerable differences exist between the three south-east Asian populations despite similar rates of atopy. Asthma and allergic disease are more strongly associated with family history than atopy, which suggests that genetic and environmental factors common to the family, other than aeroallergen sensitisation, are important in the pathogenesis of asthma and allergy in the region.

Adolescent↗
PubMed1994

Endogenous renal dopamine production regulates phosphate excretion.

We examined the effect of endogenous dopamine production on Pi and citrate excretion by Wistar rats. Carbidopa (20-40 mumol/kg ip) decreased dopamine, Pi, and citrate excretion within 20 min (86%, 47%, and 38%, respectively); Pi reabsorption increased 11 +/- 4% (P = 0.03). The decreases were sustained for at least 18 h. 3-Hydroxybenzylhydrazine (45 mumol/kg ip) reduced Pi excretion 24%. Benserazide (40 mumol/kg ip and 0.1 mumol/min iv) reduced dopamine excretion (94%) and blocked the effect of carbidopa on Pi and citrate excretion. In isolated perfused kidneys benserazide, carbidopa, and 3-hydroxybenzylhydrazine all decreased Pi excretion. Dopamine (1 mumol/l) added to cortical minceates reduced brush-border membrane vesicle (BBMV) 32P uptake by 8% (P < 0.02) and amiloride-inhibitable 22Na uptake by 19%. Carbidopa added to minceates increased 32P uptake by 12%. Carbidopa pretreatment increased (75%) amiloride-sensitive 22Na uptake into BBMV of rats fed a high-salt diet. Uptake was not increased into BBMV from rats fed a low-salt diet. Carbidopa increased (17%) basolateral membrane Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) gradually over 4 h. Na(+)-K(+)-ATPase did not increase in rats fed a low-phosphorous diet, but did increase when dopa was added to the diet. Thus endogenous dopamine appears to directly control Na(+)-Pi and Na+/H+ transport and secondarily alter basolateral membrane Na(+)-K(+)-ATPase.

Animals↗
PubMed1994

Endogenous dopamine regulates phosphate reabsorption but not NaK-ATPase in spontaneously hypertensive rat kidneys.

Dopamine's modulatory actions on signal transduction in the spontaneously hypertensive rat (SHR) proximal tubule are blunted; therefore, it was predicted that dopamine does not regulate phosphate (Pi) reabsorption in SHR. To test this hypothesis, dopamine production was inhibited with carbidopa (10 mg/kg ip) 18 h before and during clearance measurements of chronically denervated SHR and Wistar-Kyoto (WKY) rat kidneys. Dopamine excretion decreased 80% from SHR and 85% from WKY rats. Pi excretion decreased 60 to 67%. Plasma Pi and calcium, inulin clearance, and Na excretion did not change. Citrate excretion, which reflects proton secretion by proximal tubules, decreased 72% from WKY rats. Citrate excretion was significantly lower from SHR (5 +/- 10 pmol/min) than from WKY rats (73 +/- 11 pmol/min) and was not altered by carbidopa. Carbidopa, injected 18 and 1 h before kidneys were collected, increased NaK-ATPase in cortical basolateral membranes from WKY rats (27%) but not in membranes from SHR. After the incubation of renal cortical minceates for 15 min with L-DOPA (10(-5) M), there was no change in brush border membrane vesicle uptake of 32Pi, (3H)glucose, or (14C)citrate. Incubation with carbidopa (10(-4) M) increased 32Pi uptake by 11% (P < 0.001) and (3H)glucose uptake by 9% (P = 0.02). (14C)citrate uptake was not increased by carbidopa but was higher in SHR (977 +/- 2 pmol/10 s.mg) than in WKY rats (823 +/- 43 pmol/10 s.mg; P = 0.04). In summary, dopamine produced in WKY rat and SHR proximal tubules decreases Pi uptake by using a signaling process distinct from those that regulate NaK-ATPase and the antiporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

A radiation hybrid map of the BRCA1 region of chromosome 17q12-q21.

The chromosomal region 17q12-q21 contains a gene (BRCA1) conferring susceptibility to early-onset familial breast and ovarian cancer. An 8000-rad radiation-reduced hybrid (RH) panel was constructed to provide a resource for long-range mapping of this region. A large fraction of the hybrids (approximately 90%) retained detectable human chromosome 17 sequences. The complete panel of 76 hybrids was scored for the presence or absence of 22 markers from this chromosomal region, including 14 cloned genes, seven microsatellite repeats, and one anonymous DNA segment. Statistical analysis of the marker retention data employing multipoint methods provided both comprehensive and framework maps of this chromosomal region, including distance estimates between adjacent markers. The comprehensive RH map includes 17 loci and spans 179 cRays(8000). Likelihood ratios of at least 1000:1 support the 10-locus framework order: cen-D17S250-ERBB2-(THRA1, TOP2A)-D17S855-PPY-D17S190-MTBT1-GP3A++ +-BTR-D17S588-tel. The order obtained from RH mapping, when used in conjunction with other methods, will be useful in linkage analysis of breast cancer families and will facilitate the development of a physical map of this region.

Base Sequence↗