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Biomedical subjects

T Ho

Publications and source records attributed to T Ho.

At least 73 records · Page 4Linked to original sources
PubMed1991

Clinical and electrophysiological aspects of acute paralytic disease of children and young adults in northern China.

Acute peripheral nervous system diseases leading to paralysis in children are rare in Europe and the USA, whereas epidemics of a Guillain-Barré-like syndrome occur annually among children in rural parts of northern China. To clarify the features of this disorder 36 patients, aged 15 months to 37 years (median 7) with this syndrome were investigated; 91% were from rural areas. In 47%, a prodromal illness was reported in the preceding 4 weeks. Leg weakness and resistance to neck flexion were the earliest symptoms. The weakness ascended rapidly and symmetrically to affect the arms and respiratory muscles, with maximum weakness occurring a mean of 6 days after onset of weakness. Bulbar weakness occurred in 61% of patients, but only 1 had extraocular paresis. Respiratory assistance was needed by 31% of patients. Tendon reflexes were lost as weakness developed. 42% of patients had raised concentrations of protein in the cerebrospinal fluid, and the mean cell count was 3 cells/microliters (range 0-12/microliters). Electrodiagnostic studies in 22 patients showed severe reductions in motor evoked amplitudes from distal stimulation. Sensory action potentials were normal. Electromyography revealed denervation potentials in limb muscles. The distinctive epidemiological, clinical, and neurophysiological characteristics of this illness suggest that the disorder is different from both Guillain-Barré syndrome and poliomyelitis. The neurophysiological findings support the hypothesis that the disorder is a reversible distal motor nerve terminal or anterior horn cell lesion.

Acute Disease↗
PubMed1991

Gene silencing in mammalian cells by uptake of 5-methyl deoxycytidine-5'-triphosphate.

Chinese hamster ovary (CHO) cells were subjected to electroporation in the presence of 5-methyl deoxycytidine-triphosphate. This treatment increases by 10 to 100-fold the frequency of cells lacking thymidine kinase, hypoxanthine-guanine phosphoribosyltransferase, or adenine phosphoribosyltransferase. The inactivation of the genes coding for these enzymes is thought to occur following the direct incorporation of the methylated nucleotide triphosphate into DNA. The enzyme-deficient clones were stable, but almost all were reactivated at high frequency by the demethylating agent 5-azacytidine, to produce derivatives with enzyme activity. The results indicate that there is a direct relationship between DNA methylation and gene silencing.

Adenine Phosphoribosyltransferase↗
PubMed1991

Transforming growth factor alpha expression helps to distinguish keratoacanthomas from squamous cell carcinomas.

Keratoacanthomas may be difficult to distinguish histologically from squamous cell carcinomas. We studied 20 keratocanthomas and 22 squamous cell carcinomas immunohistochemically using an antibody directed against transforming growth factor alpha to determine if the pattern of transforming growth factor alpha expression would provide a useful method of differentiating these tumors. Ninety percent of the keratoacanthomas demonstrated a diffuse pattern within tumor lobules in which all but the most peripheral rim of cells were stained. A similar localization of transforming growth factor alpha was not identified in squamous cell carcinomas. In addition, 40% of the squamous cell carcinomas but none of the keratoacanthomas showed focal transforming growth factor alpha immunostaining. Our results suggest that transforming growth factor alpha expression may be a marker of epithelial differentiation and may help distinguish between these two tumors.

Carcinoma, Squamous Cell↗
PubMed1990

Integrin-associated protein: a 50-kD plasma membrane antigen physically and functionally associated with integrins.

Phagocytosis by monocytes or neutrophils can be enhanced by interaction with several proteins or synthetic peptides containing the Arg-Gly-Asp sequence. Recently we showed that an mAb, B6H12, specifically inhibited this enhancement of neutrophil phagocytosis by inhibiting Arg-Gly-Asp binding to the leukocyte response integrin (Gresham, H. D., J. L. Goodwin, P. M. Allen, D. C. Anderson, and E. J. Brown. 1989. J. Cell Biol. 108:1935-1943). Now, we have purified the antigen recognized by B6H12 to homogeneity. Surprisingly, it is a 50-kD molecule that is expressed on the plasma membranes of all hematopoietic cells, including erythrocytes, which express no known integrins. On platelets and placenta, but not on erythrocytes, this protein is associated with an integrin that can be recognized by an anti-beta 3 antibody. In addition, both the anti-beta 3 and several mAbs recognizing the 50-kD protein inhibit Arg-Gly-Asp stimulation of phagocytosis. These data demonstrate an association between integrins and the 50-kD protein on several cell types. For this reason, we call it Integrin-associated Protein (IAP). We hypothesize that IAP may play a role in signal transduction for enhanced phagocytosis by Arg-Gly-Asp ligands.

Amino Acid Sequence↗
PubMed1990

Evidence for allelic exclusion in Chinese hamster ovary cells.

Earlier results suggested that the functional hemizygosity of genes in pseudodiploid Chinese hamster ovary (CHO) cells is due to the silencing of one allele by DNA methylation. From this one could make a strong prediction that we have now been able to confirm by genetic experiments, using thymidine kinase (TK) alleles. TK- mutants induced by ethylmethane sulphonate (EMS) were all revertible to TK+ at high frequency by the demethylating agent 5-azacytidine (5-aza-CR). This revertibility was due to reactivation of a silent nonmutant TK allele. Further mutagenesis by EMS yielded TK- derivatives that were no longer revertible by 5-aza-CR; these are assumed to have mutations in both alleles. TK- cells were also transfected with equine herpes virus TK+ DNA, and the TK+ derivatives were shown to be markedly less stable than cells with the normal TK+ gene. CHO cells lack metallothionein activity (sensitive to cadmium), and also require proline for growth, because genes have become silenced during the establishment of the cell line. In both cases 5-aza-CR reactivates these genes to give the cadmium resistant and proline independent phenotypes. Long-term experiments with reactivants in the absence of selection showed that the genes become silent, presumably as a result of de novo methylation. A strain resistant to cytosine arabinoside (araCR) was also resistant to 5-azadeoxycytidine (5-aza-CdR), but not to 5-aza-CR, which would be expected if the araCR strain lacked deoxycytidine kinase.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1990

An in vitro approach to the kinetics of insulin antibodies in diabetic patients.

The purpose of this study is to evaluate the binding behavior of plasma insulin antibodies (Iab) in diabetic patients, by the following parameters: Incubation time, temperature, buffer pH, and Iab titer. We investigated the plasma insulin binding patterns of 12 insulin-treated diabetic patients, and they were separated as higher titer group (Iab = 51.9 +/- 7.28, n = 6) and lower titer group (Iab = 14.88 +/- 4.75, n = 6). The procedure was: (1) plasma samples were deinsulinized by 0.12N HCL, dextran coated charcoal suspension and 0.12N NaOH. (2) I-125 monoiodoinsulin was used to prevent artifacts resulting from variability in ligand binding due to excessive iodination, (3) separation of free and bound insulin was accomplished by rapid precipitation of hormone-antibody complex with polyethylene glycol, and (4) decanting the supernatants and counting the pellets in the automatic gamma counter. The data were obtained as the condition of incubation time, temperature, buffer pH, and Iab titer. The results obtained by the Scatchard analysis indicated that high temperature (39 degrees C vs 37 degrees C) in vitro would increase the free insulin levels and decrease the low affinity binding capacity (Q2-Q1) of Iab in patients with high titer of Iab (greater than 40%), whereas this phenomenon is not observed in patients with low affinity binding sites of Iab in patients with low titers of insulin antibodies (less than 20%).

Antigen-Antibody Reactions↗
PubMed1989

An investigation of the pathological and physiological effects of intraosseous sodium bicarbonate in pigs.

Recent interest in the intraosseous (IO) route as an alternative venous access for drug and fluid administration has increased. This study examined the physiological and skeletal pathological effects of IO NaHCO3 in pigs. In the pathological studies, swine (8-10 kg) received NaHCO3 (1 mEq/kg) in one tibia and saline (1 ml/kg) in the other tibia via an 18-gauge spinal needle inserted into the anteromedial surface of the bone. The animals were then observed for one month, sacrificed, and the tibias were isolated, sectioned, and stained for pathological examinations. The physiological effects of IO NaHCO3 infusion were studied and compared with that of intravenous (IV) administration using a cardiac arrest model as previously described. The results demonstrated that NaHCO3 had no effect on the mean arterial blood pressure and plasma catecholamine levels, but increased arterial pH values within two minutes of administration. Similar effects were found with IV NaHCO3. Pathological data indicated signs of minimal local increase in skeletal turnover associated with IO NaHCO3 infusion. It is concluded that the IO route is a safe alternative venous access for NaHCO3 administration in swine.

Animals↗
PubMed1989

Insulin resistance in obesity and noninsulin dependent diabetes mellitus.

Insulin clamp studies were carried out on 13 non-diabetics and 12 non-insulin-dependent diabetics (NIDDM). Based upon the body mass index (BMI), they were further divided into obese (BMI greater than or equal to 27 kg/m2) and nonbese groups (BMI less than 27 kg/m2). All received euglycemic insulin clamp study (Humulin-S 40mU/m2/min). Thermoregulated venous samplings were done every five minutes for measurements of plasma glucose (PG) and immunoreactive insulin (IRI). Steady state plasma glucose (SSPG) was obtained 20-80 minutes and kept for 100 more minutes. The data of final 40 minutes of clamp were used for analysis. Variations in SSPG and metabolic clearance rate of glucose (MCRG) instead of glucose infusion rate (M) value were used to assess the insulin sensitivity. The results showed that insulin resistance was noted in obese non-diabetic and diabetic subjects as well as in non-obese diabetic patients, as evidenced by higher basal IRI and lower MCRG than non-obese normal controls. Correlation analysis revealed that there was no correlation between the reduction of MCRG and the BMI in either non-diabetic or diabetic patients. There was a strong negative correlation between MCRG and the ambient fasting plasma glucose in the diabetic group, whereas this correlation was not found in the non-diabetic group. In conclusion, obesity with or without diabetes did have remarkable insulin resistance. In non-diabetic obese subjects the insulin resistance did not go up as the BMI increased further. In diabetic patients, both obesity and hyperglycemia contributed significantly insulin resistance.

Adult↗
PubMed1988

Choroidal melanoma: I-125 plaque therapy.

An iodine-125 eye plaque was used to treat 58 patients with choroidal melanoma. Patients were followed up for a mean of 48.7 months. Fifty patients had medium-sized lesions (height between 3.1 and 8.0 mm and base diameter less than 16.0 mm), and six patients had large lesions. There were 24 lesions less than 3.0 mm from the optic nerve. The average radiation dose to the apex of the tumor was 8,468 cGy (dose rate, 71 cGy per hour). Initial local disease control was achieved in 50 patients (86.2%). One patient with local treatment failure received another plaque treatment, which controlled disease, so the total disease control rate was 87.9%. Only eight patients died of their disease. Complications were similar to those with other treatment methods, but none of the patients in this study developed optic nerve atrophy.

Brachytherapy↗
PubMed1987

[Treatment of tumor hypercalcemia with clodronate. Effect on parathormone and calcitriol].

Clodronate (dichlormethylene diphosphonate) was administered to 21 patients with hypercalcemia due to malignant tumor. The drug was initially given intravenously, then orally. In 20 patients the serum calcium level had been reduced to the normal range within one week of the start of treatment (from 3.3 +/- 0.5 mmol/l to 2.4 +/- 0.3 mmol/l). With oral administration there was a renewed rise in calcium levels in some patients, which had to be treated with higher oral doses or intravenous administration. Parallel with the reduction in calcium levels there was an improvement in the originally impaired renal function. The serum level of intact parathormone(1-84) and 1.25-dihydroxy-vitamin-D3 (calcitriol) rose significantly from usually lowered initial levels. There was a non-linear inverse correlation between parathormone and calcium. No side effects were noted, even after long-term administration.

Adult↗
PubMed1987

The effect of intraosseous sodium bicarbonate on bone in swine.

Five domestic swine weighing 8 to 12 kg were anesthetized with ketamine 20 mg/kg IM and pentobarbital 20 mg/kg IV. After a sterile prep each animal received NaHCO3 1 mEq/mL/kg in one tibia and saline 1 mL/kg in the other. The animals were allowed to recover and were observed for 30 days. At the end of this period, roentgenographs were obtained of each tibia and triple phase 99m technetium bone scans were obtained. The tibias also were sectioned, stained, and examined under light microscopy for microscopic abnormalities. The only deficit found was a small cortical calcification at the site of the needle puncture in an animal that received NaHCO3. All other roentgenographs, bone scans, and microscopic specimens were normal. This study demonstrates that NaHCO3 does not have permanent adverse effects when injected into the marrow cavity of swine and supports previous clinical observations regarding the safety of NaHCO3.

Animals↗
PubMed1984

Antagonism of thromboxane A2/prostaglandin H2 by 13-azaprostanoic acid prevents platelet deposition to the de-endothelialized rabbit aorta in vivo.

The present study evaluated the direct involvement of thromboxane A2/prostaglandin H2 (TXA2/PGH2) in the process of thrombus formation at a site of vascular damage. De-endothelialization of the rabbit aorta was performed by a balloon catheter technique. Platelet deposition to the injured vessel was measured using 111Indium-labeled autologous platelets. Studies using the radiolabeled TXA2/PGH2 antagonist, 13-azaprostanoic acid (13-APA), indicated that 13-APA has an in vivo half-life of approximately 35 min and is excreted by the kidney in the metabolized form. Addition of 13-APA to rabbit plasma samples in vitro produced a dose-dependent inhibition of arachidonic acid-induced platelet aggregation. When comparable plasma levels of 13-APA were achieved by infusion of 13-APA (300 micrograms/kg/min for 90 min), a similar dose-dependency of inhibition of ex vivo aggregation was observed. Furthermore, at a plasma concentration of 40 microM, 13-APA was found to inhibit platelet deposition to the de-endothelialized rabbit aorta by 45%. Because 13-APA does not interfere with arachidonic acid metabolism, the ability of 13-APA to suppress thrombus formation is presumably due to direct antagonism of TXA2/PGH2 at the platelet receptor level. These findings, therefore, provide evidence that TXA2 and/or PGH2 have a major role in platelet deposition at a site of vascular damage.

Animals↗
PubMed1982

The reduction of platelet thrombi on damaged vessel wall by a thromboxane synthetase inhibitor in rabbits.

The role of thromboxane A2 (TXA2) in platelet-vessel wall interaction was investigated using 1-benzylimidazole (1-BI), a selective thromboxane synthetase inhibitor. 1-BI (0.9 mM) will reduce the aggregatory response of rabbit platelets to 0.2 mM arachidonate by 50% and their production of TXA2 by 84%. The effect of 1-BI on platelet thrombus formation was evaluated in vivo on New Zealand white male rabbits using the autologous indium-111 labeled platelet technique. After injection of autologous 111In-platelets, 10 cm of the abdominal aorta was de-endothelialized with a balloon catheter. Three hours later the animals were sacrificed and injured and uninjured segments of the aorta removed. The radioactivity and dry weight of the tissue were determined. The radioactivity/gm of tissue was greater for the injured tissue than for the uninjured tissue. 1-BI at 10 mg/kg reduced the specific platelet accumulation at the injured site (n = 5; 4.8 +/- 0.3 X 10(5) cpm/gm) compared to the controls (n = 10; 11.7 +/- 2.1 X 10(5) cpm/gm). Platelet accumulation on the injured tissue was further reduced by increasing the dosage to 30 mg/kg. Thirty minutes after 1-BI administration (30 mg/kg), platelets were less sensitive to arachidonate-induced aggregation (a 67% decrease) and TXA2 production was decreased 82%. Alterations in platelet sensitivity persisted for up to 3 hours. These findings indicate that TXA2 plays an important role in platelet-vessel wall interaction.

Animals↗
PubMed1980

Compactibility of granules prepared by a novel method of granulation and their dissolution.

Increasing particle size during prolonged grinding by a ballmill has been used as a novel means of producing a pharmaceutical granulation. The compactibility properties of granules of sodium chloride and of paracetamol produced by this method have been elucidated and compared with those produced by conventional granulation techniques. Force-displacement diagrams and double compactions were used to measure the net energy input on tableting. When compared with conventional granulation methods, the agglomerative phase of comminution (APOC) method produced mechanically stronger tablets with a higher dissolution rate than those compacted from granules made by a conventional wet granulation method irrespective of the compaction energy used. Tablet tensile strength is related to the elasticity and yield strength of the substance used. It is suggested that binderless tablets may be prepared using this method, thus simplifying tablet formulation and enhancing stability. A possible mechanism for the increased dissolution rate is the increased internal surfaces area of the granules produced by the prolonged grinding method.

Acetaminophen↗
PubMed1978

Energy-related pollutants in the environment: use of short-term tests for mutagenicity in the isolation and identification of biohazards.

In an effort to gather information on the potential genetic hazards of existing or proposed energy-generating or -conversion systems, we have begun a correlated analytical and genetic analysis of a number of technologies. The work is divided into two phases: one deals with known compounds expected to occur in the environment through energy production, conversion, or use; the other deals with actual samples from existing or experimental processes. To approach the problems of coping with and testing large numbers of compounds, we set up a form of the "tier system." Operating units utilizing Salmonella, Escherichia coli, yeast, human leukocytes, mammalian cells, and Drosophila have been initiated. Various liquid-liquid extraction methods and column chromatographic separations have been applied to crude products and effluents from oil-shale, coal-liquefaction, and coal-gasification processes. Mutagenicity of the various fractions is assayed by means of reversion of histidine-requiring auxotrophs of Salmonella typhimurium; comparative studies are carried out with the other genetic systems. In order to incorporate metabolic activation of these fractions and compounds, rat liver homogenates (S-9) are used in the various assays. Results implicate chemicals occurring in the basic (ether-soluble) and the neutral fractions as potential genetic hazards. Chemical constituents of these fractions (identified or predicted) were tested individually for their mutagenic activity.

Animals↗