Search PubMed⌕ Search

Biomedical subjects

J Ho

Publications and source records attributed to J Ho.

At least 91 records · Page 5Linked to original sources
PubMed1995

A teratocarcinoma developing after gross total excision of a pineal teratoma in a patient with systemic lupus erythematosus.

This is a rare case of a teratocarcinoma developing at the same site one year after the gross total excision of a mature pineal teratoma. The malignant tumour arose probably from microscopic remnants of the teratoma. This patient also suffered from systemic lupus erythematosus. Autoimmune diseases have been associated with an increased risk of malignancy, and in this case may have contributed to the malignant transformation of the teratoma.

Child↗
PubMed1995

Comparison study of DNA content of primary and metastatic lymph node lesions of colorectal cancer.

Abnormal DNA content or aneuploidy in cells usually indicates malignancy. In colorectal cancer aneuploidy has been shown to confer a poorer prognosis suggesting that aneuploid cancers are more aggressive. The mechanisms involved in the aggressive behaviour of an aneuploid tumour are still unknown. The aim of this study was to compare the patterns of aneuploidy of colorectal cancers and that of their corresponding lymph node metastases and to relate them to clinical outcomes. One hundred and one patients were studied, 81 (Dukes C) with lymph node metastasis only and 20 (Dukes D) with obvious distant metastasis as well. Forty-six (46.5%) of the tumours and an equal number of the lymph nodes were found to be aneuploid. Twenty-eight (60.9%) of the aneuploid tumours showed aneuploid metastasis and 18 (39.1%) showed diploid metastasis. Similarly, 37 (67.3%) of the diploid tumours showed diploid metastasis whereas 18 (32.7%) showed aneuploid metastasis. Local recurrence and distant metastasis were compared among the aneuploid and diploid primary tumours. Although there was no statistically significant difference, distant metastasis was more common in aneuploid tumour. Ploidy of the lymph node was not related to local recurrence or distant metastasis. We conclude that DNA ploidy by itself does not determine the metastatic potential of the tumour cell and that in about 50% of the tumours, the lymph node metastasis consists of clones of cells different from the primary tumours. We also conclude that the clinical outcome of the disease in terms of recurrence and metastasis cannot be predicted by the ploidy of the lymph node metastatic lesions.

Aneuploidy↗
PubMed1995

Disposition and cardioselectivity of MDL 74,405, a vitamin E-like free radical scavenger, in rats and dogs after intravenous infusion.

The disposition kinetics of MDL 74,405, a potent free radical scavenger for cardiac reperfusion and a vitamin E analog, was investigated in rats (1.2, 6.0, and 12 mg/kg) and dogs (1 and 10 mg/kg) after an intravenous infusion. Because the heart is the target site of drug action, a tissue distribution study was also conducted in rats (1.2 mg/kg) to explore the affinity of the drug to rat heart. In both animal species, plasma drug concentrations declined rapidly in the early distribution phase and exhibited a multiexponential pattern of elimination. Of the total excretion (95-96% of the dose) in 120 hr in rats, 45-51% was excreted in urine and 45-50% in feces. Of the total excretion (86-89% of the dose) in 120 hr in dogs, 41-43% of the dose was excreted in urine and 41-43% in feces. The dose was excreted mainly unchanged (62-78% in rat and 80-86% of the dose in dog urine) with several potential minor metabolites, indicating that renal and biliary excretions are the two major, equally important, routes of drug elimination in both species. Rats cleared the drug from the body markedly faster than dogs: the mean residence time in rats. (1.9-3.2 hr) was 15-20 times shorter, the terminal elimination half-life in rats (3.6-7.0 hr) was 10 times shorter; and the total clearance in rats (148-216 ml/min/kg) was 6-9 times greater. The steady-state volume of distribution was very large for both species. (19-37 liters/kg for rats and 59-64 liters/kg for dogs), which is consistent with the extensive tissue uptake of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Prophylactic ganciclovir is more effective in HLA-identical family member marrow transplant recipients than in more heavily immune-suppressed HLA-identical unrelated donor marrow transplant recipients. Australasian Bone Marrow Transplant Study Group.

A multi-centre Australasian study of the efficacy of prophylactic ganciclovir in 88 recipients of marrow allografts at high risk for post-transplant cytomegalovirus (CMV) disease was conducted. The actuarial incidence of CMV disease was 10% in 74 recipients of HLA-identical family member transplants given ganciclovir but was 33% in 14 recipients of HLA-identical unrelated donor transplants given more immune-suppression pre- and post-transplant (P = 0.006). CMV disease developed in 4 of the 14 recipients of HLA-identical unrelated donor transplants at a median of 59 days post-transplant and was associated with concurrent graft-versus-host disease (GVHD) in 2 of the 4. CMV disease occurred in 5 of 74 recipients of an HLA-identical family member transplant at a median of 137 days post-transplant and was associated with concurrent moderate to severe GVHD in 4 of the 5. Thus the risk of CMV disease was higher in recipients who were not genotypically identical for HLA with their donors and who (in consequence) were given more immune-suppression than HLA-identical family member transplant recipients. Additionally, CMV disease can occur beyond the period of prophylactic ganciclovir administration (first 3 months post-transplant) in patients developing significant chronic GVHD and prophylaxis should be reintroduced at that time in such patients.

Adolescent↗
PubMed1994

Breakpoint cluster region gene product-related domain of n-chimaerin. Discrimination between Rac-binding and GTPase-activating residues by mutational analysis.

The breakpoint cluster region gene product (Bcr) is a GTPase-activating protein (GAP) for members of the Rho family, Cdc42Hs, and Rac1, as is the brain protein n-chimaerin. At least 15 proteins have sequence identity to the GAP domain (150 amino acid residues) of Bcr. The widespread occurrence of proteins that possess sequence identity to the Bcr-related GAP domain makes it especially important to understand its structure/function relationships. Amino acid sequence alignment of these proteins reveals three blocks of conservation in the GAP domain. Here, we present a mutational analysis of this domain using n-chimaerin sequences. Ten mutations were constructed (at least two in each of the blocks of conservation), expressed as glutathione S-transferase fusion proteins in Escherichia coli, and purified. Seven of the mutants, including deletions, still possessed GAP activity for Rac1. Three of the mutants had no Rac1-GAP activity but were still able to bind Rac1. IC50 values obtained from competition experiments suggest that n-chimaerin and the mutants with no GAP activity bound Rac1 with similar apparent binding constants. Thus, this mutant analysis allows discrimination between Rac1-binding and Rac1 GTPase- activating residues.

Amino Acid Sequence↗
PubMed1994

Response to thymectomy in Chinese patients with myasthenia gravis.

Myasthenia gravis was diagnosed in 48 patients between 1985 and 1991 in this Chinese community. Thymectomy was performed on 36 patients and the mean postoperative follow-up period was 49 months. Significant improvement was seen in 72% of the thymectomised patients, with 33% achieving complete remission. Patients with mild generalised myasthenia at presentation or those found to have thymic hyperplasia had the best prognosis. Patients with more severe symptoms or those with an underlying thymoma also responded favourably. Only patients with ocular myasthenia or those with a normal or atrophic thymus gland had no more than an even chance of gaining significant improvement. Although previous reports suggested a high prevalence of ocular myasthenia and of thymoma among Chinese myasthenic patients, the present study has found no evidence that they respond differently to thymectomy than their Western counterparts.

Adolescent↗
PubMed1994

Early sperm-egg interaction after sperm microinjection.

The early events of sperm-egg interaction occurring 1-3 h after multiple sperm injection into the perivitelline space (PVS) and after direct injection into the ooplasm of human oocytes are reported. The sperm acrosome reaction occurred in the PVS but was not detected within the ooplasm. Sperm in the PVS were incorporated into the ooplasm in the usual manner described in vitro, after completion of the acrosome reaction, and a block to polyspermy was evident at the oolemma. However, sperm incorporation into the ooplasm was not clearly defined and requires further investigation. Sperm were also incorporated into oolemma-bound vacuoles within the ooplasm and breaches in the ooplasm were seen after intracytoplasmic injection. Both normal and abnormal sperm were found in the PVS and ooplasm, even though sperm from donors with normal semen parameters were used. The effect of freezing in liquid nitrogen on demembranation of sperm for microinjection is also reported.

Acrosome↗
PubMed1994

In situ detection of Epstein-Barr virus in gastric and colorectal adenocarcinomas.

The association of Epstein-Barr virus (EBV) with lymphoepithelioma-like carcinoma in the nasopharynx, which is common in Chinese from the southern region, is well established. Recently, EBV has also been found to be associated with lymphoepithelioma-like carcinomas (LELCs) and carcinomas with prominent lymphoid infiltrates in the stomach. We investigated for the presence of EBV in 74 cases of gastric adenocarcinoma and 36 cases of colorectal adenocarcinoma from Chinese patients by in situ hybridization (ISH) using an antisense EBER probe. In seven cases (9.5%) of gastric carcinoma, EBER was highly expressed in the adenocarcinoma cells and metastatic tumor cells in regional lymph nodes. In all these cases, the normal gastric epithelium was EBV negative. None of the colorectal carcinomas showed a positive signal. Isolated positive lymphoid cells were frequently found in both tumors. Of the seven positive cases, only one was LELC, and the others were conventional adenocarcinomas of the intestinal type. Five showed expression of the viral RNA in all tumor cells as well as the surrounding dysplastic epithelium. Interestingly, the sixth case showed distinct negative islands of dysplastic glands adjacent to strongly positive dysplastic glands and invasive carcinoma cells. This pattern of positivity, together with negative normal gastric epithelium and positive metastatic tumor, suggested that EBV infection occurred in the dysplastic phase and that an apparent growth advantage was conferred by the EBV infection.

Adenocarcinoma↗
PubMed1994

Influence of chronic nicotine intake and acute ethanol challenge on gastric mucus level and blood flow in rabbits.

The effects of nicotine pretreatment on ethanol-induced gastric mucosal lesions and changes of gastric mucosal mucus levels and blood flow (GBF) were studied in anaesthetized rabbits. Nicotine treatment 25 or 50 micrograms/ml drinking water did not affect the volume of water consumption during the 10-day experimental period. It did not produce gastric mucosal lesions or affect the superficial adherent mucus content. The length of mucus-containing cells and the basal GBF were also unaffected. Intragastric administration of absolute ethanol reduced GBF, this effect was not altered by nicotine. However, the alkaloid potentiated the ulcerogenic actions of ethanol both on lesion formation and mucus depletion evoked by graded oral doses of ethanol (50 or 100%, v/v). Ultrastructurally, the mucous cells were more degenerated in the animals co-treated with nicotine and ethanol. It is concluded that reductions of mucus-containing cells and adherent mucus on the gastric mucosa are likely to be the contributory factors involved in the aggravating action of nicotine on ethanol-induced gastric mucosal lesions in rabbits.

Animals↗
PubMed1994

Role of Na(+)-H+ exchange in mediating effects of endothelin-1 on normal and ischemic/reperfused hearts.

Endothelin (ET) has been shown to be elevated under conditions of cardiac pathology and to produce diverse cardiac effects, including coronary constriction and a positive inotropic influence. We characterized the concentration- and time-dependent effects of the most potent of the ET isoforms, ET-1 (0.4, 2, and 4 nmol/L), on myocardial contractility and coronary resistance and assessed its effects on the ischemic and reperfused heart. Because ET-1 has been shown to activate the Na(+)-H+ exchanger in cardiac myocytes, we determined the contribution of the antiport by examining the effects of ET-1 in the presence of the Na(+)-H+ exchange inhibitor methylisobutyl amiloride (MIA). At all three concentrations, ET-1 produced an initial positive inotropic effect that was reversed with continued perfusion, the degree of the reversal being dependent on ET-1 concentration. With 0.4 nmol/L, contractility returned to pre-ET-1 values, whereas after 75 minutes of perfusion with 4 nmol/L ET-1, contractility was depressed by 75%. At all concentrations, ET-1 produced a coronary-constricting effect, whereas an elevation in resting tension was observed only with 4 nmol/L ET-1. MIA significantly prevented the positive inotropic effect of ET-1 but had no effect on loss in function or elevation in resting tension produced by 4 nmol/L ET-1. Furthermore, MIA partially, but not significantly, attenuated the constricting effects of all ET-1 concentrations. In the ischemic heart, 0.4 nmol/L ET-1 appeared to delay the loss in contractility produced by cessation of flow, although the effect was not significant. Higher concentrations of ET-1 were without effect on ischemia-induced contractile depression, although their presence produced a marked elevation in resting tension during ischemia that was attenuated by MIA. Recovery in contractility was reduced by all concentrations of ET-1, although the effects of the lowest concentration were associated primarily with defective relaxation. The depressant effects of ET-1 either in normal or ischemic/reperfused hearts were irreversible. The inhibitory effects of ET-1 on contractile recovery were associated with diminished tissue glycogen and elevated lactate levels. High-energy phosphates after reperfusion were depressed in hearts treated with 4 nmol/L ET-1. The attenuation in contractile recovery and alterations in metabolite content were prevented by MIA. These results provide evidence that ET-1 produces complex effects on heart function that are likely mediated via different mechanisms and demonstrate its ability to aggravate ischemic and reperfusion injury through a mechanism possibly involving Na(+)-H+ exchange activation.

Animals↗
PubMed1994

The multifocality of bronchioloalveolar lung carcinoma: evidence and implications of a multiclonal origin.

Bronchioloalveolar lung carcinoma (BAC) is a unique type of lung cancer with distinguishing pathologic, biologic, epidemiologic, and perhaps etiologic features that set it apart from all other forms of lung cancer, including general adenocarcinoma, into which it is traditionally grouped. Recent studies at our institution have demonstrated a near exponential increase in BAC cases with 25% showing evidence of multifocality. Although some theories suggest that this multifocality is caused by intrapulmonary aerosol/aspiration or lymphatic spread, this study provides evidence for multiclonality as the basis for some cases of multifocal BAC by exploiting a novel strategy for clonality determinations that involves polymerase chain reaction amplification of a 511-base pair region located within the first intron of the human hypoxanthine phosphoribosyltransferase gene, a site that contains inactive X chromosomal obligately methylated HpaII/MspI sites and single-base allelic polymorphisms in 5 to 10% of females. BAC cells, obtained by enzymatic dissociation of different fresh/paraffin-embedded tumoral foci from polymorphic individuals with multilobar or bilateral BAC, were sorted to homogeneity with a fluorescein-conjugated anticarcinoembryonic antigen and then subjected to genomic DNA extraction and HpaII digestion before polymerase chain reaction amplification and subsequent analysis of the product on denaturing gradient gel electrophoresis. The differing migrations of the single homoduplexes generated were indicative of BAC clonal nonidentity or multiclonality in three separate cases. The demonstration of multiclonality in some cases of BAC provides an alternate explanation for multifocality.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1993

Contribution of loops and nicks to the formation of DNA dumbbells: melting behavior and ligand binding.

We have evaluated the thermodynamic contribution of thymine loops and nicks to the overall stability of double-helical DNA by investigating (1) the melting behavior of two unligated DNA dumbbells and their corresponding core duplexes and (2) the association of netropsin to the central core of four A.T base pairs of these molecules. Temperature-dependent UV absorption and differential scanning calorimetry techniques have been used to characterize the helix-coil transitions of all four deoxyoligonucleotide duplexes. In 10 mM NaP(i) buffer at pH 7.0, all transitions were monophasic. The dumbbells melt with transition temperatures, Tm, independent of strand concentration, while each duplex melts with transition temperature dependence on strand concentration, characteristic of mono- and bimolecular processes, respectively. The Tm's for the dumbbells correspond to those of single hairpins containing only four base pairs in the stem. We obtain dTm/d log [Na+] values of 10.9-12.5 degrees C for these molecules, which correspond to similar counterion releases and suggest helical structures with similar charge densities and helical strandedness. Standard thermodynamics profiles at 5 degrees C reveal that the favorable free energy of forming these ordered structures results from the partial compensation of favorable enthalpies with unfavorable entropies. The stabilization of the dumbbells relative to the core duplexes is enthalpic, due to extra stacking of the nearest loop thymines on the G.C base pairs at both ends of the stem.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1993

Surgical lateral clearance in resected rectal carcinomas. A multivariate analysis of clinicopathologic features.

BACKGROUND: Incomplete removal of the tumor is the main cause of local recurrence in rectal carcinomas; this often occurs at the lateral aspects devoid of the peritoneum. The authors examined prospectively 80 resected rectal carcinoma specimens in an attempt to discover a reliable method to detect lateral resection margin (LRM) involvement by these tumors and to identify pathologic factors that would be prognostically important. METHODS: In each of the 80 resected specimens, the whole tumor was embedded, and whole-mount sections of the entire tumor and the surrounding mesorectum were examined after serial transverse slicing. The distance from the outermost part of the tumor to the LRM (surgical clearance) was measured. RESULTS: Six (7.5%) of the 80 specimens showed LRM involvement (defined as surgical clearance < or = 1 mm) in the single slice seen macroscopically to have the deepest tumor invasion, whereas 16 specimens (20%) were found to have LRM involved after examining all slices microscopically. Surgically clearance had a strong inverse relationship with Dukes staging (P < 0.001) and depth of tumor invasion (P = 0.001). The overall local recurrence rate was 28%; it was much higher (53%) in the patients who had LRM involved by tumor. As a whole, local recurrence was related significantly to LRM involvement (P = 0.006). Survival rates were correlated with macroscopic (n = 3) and microscopic (n = 13) features of the resected specimens using Cox multivariate regression analysis. Three of the nine pathologic parameters isolated (i.e., surgical clearance, cellular differentiation, and number of involved pericolic lymph nodes) were identified as favorable independent prognostic factors. CONCLUSIONS: Local recurrence is related closely to LRM involvement. Embedding and examining the entire tumor and mesorectum is the only reliable and satisfactory means of assessing LRM. Detailed pathologic study on the resected tumor is important when assessing the prognosis.

Adenocarcinoma↗
PubMed1993

Cocaine and metabolites in the hair of ancient Peruvian coca leaf chewers.

Cocaine and its metabolites, benzoylecgonine (BZE) and ecgonine methylester (EME), were found in hair samples from ancient Peruvian coca-leaf chewers dating back to AD 1000. Hair was analyzed by gas chromatography/mass spectrometry (GC/MS) to quantitate the concentrations. The two metabolites were found in higher concentration than the parent drug. The metabolite levels appear to be below that of modern cocaine abusers. Gender does not appear to be a factor in the incorporation of drug into hair.

Adult↗