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Biomedical subjects

L T Ho

Publications and source records attributed to L T Ho.

180 records · Page 10Linked to original sources

Calcium buffering capacity of human seminal plasma: the role of EGTA in stimulating sperm motility.

The role of EGTA in stimulating human sperm motility (reported in Lancet i: 460-461, 1984) was investigated by measuring the calcium buffering capacity of human seminal plasma. Human seminal plasma contains 9.5 +/- 1.1 mM (mean +/- SE) calcium of which 0.16 +/- 0.01 mM only exists as free Ca2+. The free Ca2+ concentration was not changed by the addition of either 1 mM CaCl2 or 1 mM EGTA. The ability of seminal plasma to bind calcium ions was determined by adding varying amounts of CaCl2. Scatchard analysis of the results indicates the presence of high amounts of high-affinity (Kd1 = 3.4 +/- 0.2 microM, Bm1 = 11.5 +/- 1.5 mM) and low-affinity (Kd2 = 0.55 +/- 0.04 mM, Bm2 = 30.4 +/- 1.7 mM) Ca2+-complexing agents. The low-affinity Ca2+-binding substance may be citrate. These results seem to suggest that human seminal plasma has a high Ca2+ buffering capacity and the stimulation of sperm motility by EGTA ought to be mediated via a mechanism other than the reduction of the free calcium concentration in semen.

Calcium↗

Diurnal variation of insulin clearance and sensitivity in normal man.

Sixteen normal healthy volunteers were randomized into two groups, receiving either low doses insulin infusion clamp study (8mU/M2/min) or high dose (40mU/M2/min) to determine the diurnal insulin clearance and sensitivity. Each subject received the assigned dose of insulin clamp twice; one in the morning (0800-1000) and the other in the evening (1800-2000), each with a precedent 9 hours of fasting, respectively. The results showed that there were diurnal variation of serum insulin clearance in the high dose study (AM:791 +/- 54ml/min/M2, PM:947 +/- 53ml/min/M2, p less than 0.01), and the small dose study (AM:411 +/- 32ml/min/M2, PM:716 +/- 87ml/min/M2, p less than 0.001). Diurnal variation of insulin sensitivity as judged by dividing glucose infusion rate by the ambient serum free insulin level (M/FI ration), was only noted in the low dose insulin infusion clamp study (AM:14.6 +/- 2.4, PM:10.5 +/- 1.1, p less than 0.05). In summary, at low physiological levels of insulin the insulin sensitivity is better in the morning, whereas at both high and low insulin levels the insulin clearance of normal subject is greater in the evening. The mechanism of this diurnal variation of insulin clearance and sensitivity awaits further studies.

Adult↗

Hypothalamic involvement in the locomotor stimulant or satiety action of thyrotropin-releasing hormone and amphetamine.

To determine whether the locomotor stimulant and the anorexic actions of thyrotropin-releasing hormone (TRH) and amphetamine were mediated through the hypothalamic nuclei, rats were infused with either TRH or amphetamine through previously implanted hypothalamic cannulae. Administration of TRH or amphetamine into the ventromedial hypothalamus, but not the lateral hypothalamus and the anterior hypothalamus, caused locomotor stimulation in rats. On the other hand, administration of TRH or amphetamine into the lateral hypothalamus, but not the ventromedial hypothalamus or the anterior hypothalamus, caused a reduction in food consumption without affecting relative water intake (or water-to-food ratio) in the rat. The data indicate that the ventromedial hypothalamus is the most sensitive site of the TRH- or amphetamine-induced locomotor stimulation and the action of TRH or amphetamine on the lateral hypothalamus is also a possible mechanism mediating anorexia.

Amphetamine↗

The antilipemic effectiveness of pentaerythritol tetranicotinate on hyperlipidemic patients with or without diabetes mellitus--a double-blind, randomized and two-period change-over experiment.

Pentaerythritol tetranicotinate (Perycit), at an oral dosage of 750 mg daily, was given to 12 patients with idiopathic hyperlipidemia and to 12 patients with hyperlipidemia superimposed with diabetes mellitus (DM). With 2 months off-drug period as the baseline, each patient then received 3 months of placebo and 3 months of Perycit. The sequence of treatment was randomized and balanced in frequency. Blood glycosylated hemoglobin (Hb A1) and fasting plasma glucose (FPG) were used as indices of diabetic control. Serum triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and TC/HDL-C ratio were measured and calculated in order to compare the antilipemic effectiveness of Perycit with that of placebo. The non-parametric Wilcoxon test was used for the statistical analysis. The results showed that in the idiopathic group, Perycit significantly lowered the serum level of TG and the ratio of TC/HDL-C, and elevated the serum level of HDL-C. In the diabetic group, although there was a similar improvement in diabetic control in both periods of placebo and Perycit treatments, there was no change in the serum levels of TG and HDL-C. There was a slight increase of the serum levels of TC in the periods of Perycit treatment, whereas a small increase of HDL-C resulted in a mild decrease of the TC/HDL-C ratio. There was mild and transient facial flushing during the Perycit treatment in 6 out of 12 diabetic patients. Otherwise, there was no side effects in either group. Pooling the two groups' data together, Perycit increased the serum levels of HDL-C and decreased the TC/HDL-C ratio. It is concluded that Perycit has antilipemic effects in patients with idiopathic hyperlipidemia, and may be helpful in reducing the atherogenic risks in these patients. In patients with hyperlipidemia superimposed with DM, although the serum lipids composition was not significantly changed after Perycit, the atherogenic risks might also be reduced as demonstrated by the decrease of the TC/HDL-C ratio.

Clinical Trials as Topic↗

Characterization of human growth hormone from acromegalic pituitary tumors.

Human growth hormone (HGH) was extracted from acromegalic pituitary tumors at pH 10.5 and precipitated with ammonium sulfate at 20-40% saturation. It was purified on a Sephadex G-100 column to yield monomeric HGH. The tumor-HGH was indistinguishable from the authentic one in polyacrylamide gel electrophoresis at pH 8.3 or in the presence of sodium dodecyl sulfate, high-performance liquid chromatography, radioimmunoassay, peptide map, amino acid composition and N-terminal partial amino acid sequence. The tumor-HGH is active in the tibia assay and bodyweight gain test in hypophysectomized rats with comparable potency to that of the authentic sample.

Acromegaly↗

A therapeutic trial of bezafibrate on patients with hyperlipidemia with or without diabetes mellitus.

Bezalip (bezafibrate), at an oral dosage of 200 mg three times a day, has been used on 12 patients with idiopathic hyperlipidemia, and on 12 patients with hyperlipidemia superimposed with diabetes mellitus. Each patient received bezafibrate for 3 months and placebo for 3 months. Blood glycosylated hemoglobin (HbA1) and fasting plasma glucose (FPG) were used as indices of diabetic control. Serum triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), and TC/HDL-C ratio were measured and calculated in order to compare the antilipemic effects of bezafibrate with that of placebo. Non-parametric Wilcoxon test was used for statistical analysis. In both the idiopathic group and diabetic group, bezafibrate significantly lowered the serum levels of TG and TC/HDL-C, as well as elevated the level of HDL-C. The serum TC levels were not significantly altered in either of the groups. These effects could not be ascribed to an improved diabetic control, since the percent changes of HbA1 were not different between the bezafibrate periods and the placebo periods. There were no significant facial flushing, nor other side effects during the treatment with bezafibrate. It is concluded that bezafibrate has antilipemic effects, and may be helpful in reducing the atherogenic risks.

Administration, Oral↗

Effects of anterior pituitary hormones and their releasing hormones on physiological and behavioral functions in rats.

The effects of direct administration of TRH, TSH, LHRH, LH, ACTH, GH, FSH and prolactin into cerebral ventricle system on metabolic, respiratory, cardiovascular and behavioral responses were assessed in unanesthetized rats, Intraventricular administration of TRH, TSH, LHRH or LH caused hypothermia, decreased metabolism and/or cutaneous vasodilation at room temperature (22 degrees C). Intraventricular administration of FSH, ACTH or prolactin caused hyperthermia, increased metabolism and/or cutaneous vasoconstriction. Intraventricular administration of GH caused an insignificant change in thermoregulatory responses. There was no change in respiratory evaporative heat loss in response to either of the drugs tested. In addition, intraventricular administration of TRH, LHRH or LH caused tachycardia, hypertension and a reduction in the epinephrine-induced reflex bradycardia. In contrast, intraventricular administration of prolactin caused bradycardia, hypotension and an enhancement in the epinephrine-induced reflex bradycardia in conscious rats. There was no change in cardiovascular function in response to intraventricular administration of TSH, FSH, ACTH or GH. Furthermore, following intraventricular administration of TRH, but not TSH, LHRH, LH, FSH, GH, ACTH or prolactin three main categories of behavior were provoked: activity of normal type--forward locomotion stimulation, head and body rearing; stereotype activity--increased grooming and head swaying; and abnormal type behavior--tail elevation and piloerection in rats. The data indicate that most of the anterior pituitary hormones and their releasing hormones act through a central mechanism to influence physiological and/or behavioral functions.

Animals↗

The lack of effects of somatostatin on gastric responses induced by electrical vagal stimulation.

The effects of somatostatin on ulcer formation, gastric acid secretion and histamine release were assessed during vagus nerve stimulation in rats. Direct electrical vagal stimulation significantly increased histamine release and acid output in gastric secretion but decreased mast cell counts in gastric glandular mucosa. Hemorrhagic ulceration on the gastric glandular mucosa was also observed. Somatostatin pretreatment (10 micrograms/kg) did not inhibit gastric ulcer formation, gastric acid secretion or histamine release induced by vagal stimulation. Cimetidine (an H2 blocker) pretreatment, however, significantly decreased gastric acid secretion as well as ulcer formation. The present study indicates the direct vagal stimulation increases gastric acid secretion and ulcer formation. These effects are partially histamine dependent. Somatostatin did not inhibit histamine release induced by vagal stimulation and reflects the inability of the drug to prevent ulcer formation and gastric output under these conditions in rats. However, the inhibition of basal gastric acid secretion produced by somatostatin might be useful clinically in humans.

Animals↗

A dopamine-acetylcholine link in the caudate-putamen complex which mediates metabolic rate.

In order to investigate the possible involvement of the dopaminergic and the cholinergic neurons of caudate-putamen complex (CP) in temperature regulation, we have assessed the effects of administration of either acetylcholine (Ach), atropine (Ach receptor antagonist), apomorphine (DA receptor agonist), or haloperidol (DA receptor antagonist) into the CP on metabolic, respiratory, vasomotor and temperature responses in conscious rats at various ambient temperature (Ta). The results show that intra-CP injection of either Ach or apomorphine caused hypothermia, decreased metabolism and cutaneous vasoconstriction at Ta 8 and 22 degrees C, as well as hyperthermia and cutaneous vasoconstriction at Ta 30 degrees C. On the other hand, intra-Cp injection of either atropine or haloperidol caused hyperthermia, increased metabolism and cutaneous vasoconstriction at all Ta (8, 22, and 30 degrees C) studied. There was no change in respiratory evaporative heat loss in response to these agents at all Ta studied. Furthermore, the Ach-induced hypothermia or hypo-metabolism was antagonized by pretreatment with atropine, but not with haloperidol. However, the apomorphine-induced hypothermia or hypo-metabolism at Ta 8 and 22 degrees C was antagonized by pretreatment with either atropine or haloperidol. These observations tend to indicate that a dopamine-acetylcholine link occurs in the caudate-putamen complex which mediate metabolic rate in the rat.

Acetylcholine↗

Using semi-automated oscillometric blood pressure measurement in diabetic patients and their offspring.

To determine whether a semi-automatic oscillometric blood pressure (BP) monitor Dinamap 1846SX (DIN) can replace the standard mercury sphygmomanometer (SMS) for BP measurements in diabetic patients and their offspring, we compared SMS with DIN in 105 diabetic patients and their families. Their mean age was 50.6 (range 24-86) years, of whom 41 had diabetes mellitus (DM), 32 impaired glucose tolerance and 32 non-DM. After resting quietly for 10 min, their right arm BP were measured twice with each device at random and with 1-min intervals between each measurement. Agreement between measurements was tested by plotting the differences between the methods against means and by intraclass correlation coefficient (r(I)). The DIN was also evaluated by the criteria of American Association for the Advancement of Medical Instrumentation (AAMI), the British Hypertension Society (BHS) criteria and clinical criteria of O'Brien. All measurements by DIN [first readings or averaged readings of duplicate measurements of systolic BP (SBP) or diastolic BP (DBP)] satisfied the AAMI criteria and had good agreement with SMS (r(I)=. 951 for SBP and r(I)=.905 for DBP). The first readings of systolic BP measured by DIN vs. SMS failed to satisfy the criteria by O'Brien and reached BHS grade C level. Other measurements passed the limits of O'Brien and reached BHS grade A or B. In conclusion, averaged readings of duplicate BP measurements by DIN are interchangeable with that by SMS in Chinese diabetic patients and their offspring. Only one single DIN measurement is not acceptable for clinical application.

Adult↗

Dialysis-related amyloidosis: history and clinical manifestations.

Dialysis-related amyloidosis (DRA) or beta(2)-microglobulin amyloidosis (A beta(2)M) is a unique type of amyloidosis that has been described in individuals with both long-standing chronic renal disease and end-stage renal disease (ESRD). It has been associated with serious complications that significantly add to the morbidity of long-term dialysis patients. The deposition of beta(2)M in amyloid fibrils in various joint and osteoarticular surfaces leads to the clinical complaints and findings typical of this disorder. However, a visceral form with systemic organ involvement has also been described. Despite advances in the understanding of this disorder and in the delivery of dialysis, the ability to alter the incidence of DRA and its course remains uncertain.

Amyloidosis↗

Microencapsulation and controlled release of insulin from polylactic acid microcapsules.

Insulin has been encapsulated in biodegradable polylactic acid microcapsules and non-biodegradable ethylcellulose microcapsules by using an emulsification-solvent evaporation process. Gelatin and polyvinylalcohol were used as protective colloids. The concentrations and types of protective colloids affecting the micromeritic properties and release behavior of insulin microcapsules were studied. The higher the concentration of protective colloids the smaller the particle size of microcapsules. The median diameter of microcapsules decreased with the increase of the viscosity of protective colloids. Scanning electron microscopic observations suggested that microcapsules prepared from higher concentrations of polyvinylalcohol solution resulted in a nonporous and compact surface on the microcapsules, compared to the porous microcapsules prepared from gelatin solution. The residual crystals and porous structure of microcapsules affected the release rate of microcapsules. After the initial burst effect the release rate of insulin from microcapsules was found to be constant, so that prolonged release was obtainable. Three percent of polyvinylalcohol was the best choice for the preparation of polylactic acid microcapsules.

Biocompatible Materials↗

Recombinant human growth hormone (Genotropin) in treatment of children with growth hormone deficiency: the first year observation.

Five prepubertal children with previously untreated growth hormone deficiency were enrolled in this trial and treated with authentic recombinant human growth hormone hGH, 0.1 IU/Kg/day, subcutaneously, for one year. All of the children markedly increased their growth rate; the height velocity increased from 3.4 +/- 0.7 cm/yr to 11.3 +/- 2.0 cm/yr during one year's treatment. The height-standard deviation score for chronological age increased from -4.03 +/- 0.52 to -2.70 +/- 0.68. The bone age increased from 5.6 +/- 1.5 year before treatment to 6.4 +/- 1.6 years after one-year treatment. Only one child acquired low titer anti-hGH antibodies during the course of treatment (1:2 to 1:6). No untoward symptoms were complained of by these children and no biochemical abnormalities occurred except transient subclinical hypothyroidism in one child during the treatment course.

Body Height↗

Modification of adenylate cyclase by photoaffinity analogs of forskolin.

Photoaffinity labeling analogs of the adenylate cyclase activator forskolin (PF) have been synthesized, purified and tested for their effect on preparations of membrane-bound, Lubrol solubilized and forskolin affinity-purified adenylate cyclase (AC). All analogs of forskolin significantly activated AC. However, in the presence of 0.1 to 0.3 microM forskolin, the less active forskolin photoaffinity probes at 100 microM caused inhibition. This inhibition was dose-dependent for PF, suggesting that PF may complete with F for the same binding site(s). After cross-linking [125I]PF-M (see Figure 1 for structure) to either membrane or Lubrol-solubilized AC preparations by photolysis, a radiolabeled 100-110 kDa protein band was observed after autoradiography following SDS-PAGE. F at 100 microM blocked the photoradiolabeling of this protein. Radioiodination of forskolin-affinity purified AC showed several protein bands on autoradiogram, however, only one band (Mr = 100-110 kDa) was specifically labeled by [125I]PF-M following photolysis. The photoaffinity-labeled protein of 100-110 kDa of AC preparation of rat adipocyte may be the catalytic unit of adenylate cyclase of rat adipocyte itself as supported by the facts that [a] no other AC-regulatory proteins are known to be of this size, [b] the catalytic unit of bovine brain enzyme is in the same range and [c] this PF specifically stimulates AC activity when assayed alone, and weekly inhibits forskolin-activation of cyclase. These studies indicate that radiolabeled PF probes may be useful for photolabeling and detecting the catalytic unit of adenylate cyclase.

Adenylyl Cyclases↗

Production and assay of antibodies to an activator of adenylate cyclase, forskolin.

Forskolin is a unique diterpene activator of adenylate cyclase which has been extensively used in the study of cAMP generating systems. This report describes the production of antibodies to forskolin and the optimization of two sensitive assay methods for such antibodies. 7-0-Hemisuccinyl 7-deacetyl forskolin, coupled to either human serum albumin or goat IgG, was injected into goats to elicit antibodies to the forskolin hapten. Two assay methods, a radioimmunoassay with [12-3H]forskolin as a tracer and a colorimetric enzyme-linked immunosorbent assay (ELISA) with horse radish peroxidase-labelled rabbit anti-goat IgG as an indicator, were optimized to test for the presence of forskolin antibodies in antisera and isolated IgG fractions. The titers for forskolin antisera were 4000-10000. Both assay methods can be adapted to quantify forskolin and its protein conjugates. The availability of antibodies to this diterpene will be useful in accelerating the understanding of the mechanism of adenylate cyclase activation by forskolin.

Adenylyl Cyclases↗