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Biomedical subjects

K K Ho

Publications and source records attributed to K K Ho.

At least 145 records · Page 8Linked to original sources
PubMed1993

Regulation of growth hormone binding protein in man: comparison of gel chromatography and immunoprecipitation methods.

GH circulates in part bound to a high affinity binding protein (GHBP). Gel chromatography is the established method for measuring GH binding activity in plasma, but is slow and tedious. The separation of bound from free GH by immunoprecipitation using a monoclonal antibody to the GH receptor may be a more practical alternative. We have examined the effects of GH and estrogen status on GHBP measured in 24-h pool samples and compared results obtained from gel filtration and immunoprecipitation. GHBP activity (percent specific binding of [125I]GH) was measured in normal, GH-deficient, and acromegalic subjects; and in two groups of postmenopausal women before and after oral (ethinyl estradiol 20 micrograms daily) or transdermal (17 beta-estradiol 100 micrograms daily) estrogen therapy. GHBP activity was not significantly different between normal, GH-deficient, and acromegalic subjects matched for age and sex. Neither GH administration to GH-deficient and normal subjects, nor octreotide treatment of patients with acromegaly, significantly altered GHBP activity. Oral estrogen treatment significantly increased GHBP activity. This change was associated with an increase in binding capacity (P = 0.001) but not affinity, as revealed by Scatchard analysis. GHBP activity did not change significantly with transdermal estrogen therapy. GHBP activity obtained by the two methods was significantly correlated (n = 70, r = 0.92, P = 0.001) although values for the antibody method were 25% higher. Similarly, capacity estimates were highly correlated (r = 0.90, P = 0.0001), with values by immunoprecipitation being 40% higher. We conclude that GH secretory status is not a determinant of GHBP. Oral estrogens increase GHBP activity through an increase in capacity and not affinity. The estrogen effect is route dependent and the oral response is likely to reflect a first pass hepatic effect. The higher binding activity and capacity estimated from immunoprecipitation are likely to reflect a more rapid separation process thereby minimizing dissociation of GHBP complex. Immunoprecipitation offers the advantages of simplicity, convenience, and accuracy for the measurement of GH binding activity and GHBP concentrations in serum.

Acromegaly↗
PubMed1993

Activation of the somatotropic axis by testosterone in adult males: evidence for the role of aromatization.

To determine whether testosterone modulates the somatotropic axis in adult males, we compared 24-h GH secretion (from 20-min sampling, using Cluster analysis) and insulin-like growth factor-I (IGF-I) levels of five hypogonadal men (aged 20-32 yr) with those of six normal men (aged 21-27 yr), and examined the effects of testosterone replacement (testosterone enanthate 250 mg im monthly). To elucidate whether the action of testosterone on the somatotropic axis is direct, or requires the aromatization of testosterone to estradiol, we also examined the effects of the nonsteroidal antiestrogen, tamoxifen (20 mg/day for 3 weeks), on 24-h GH secretion and IGF-I levels in the normal men and in four of the hypogonadal men during concurrent testosterone treatment. Compared to the normal men, the hypogonadal men had significantly reduced mean GH pulse amplitude (3.1 +/- 0.6 vs. 8.4 +/- 1.7 micrograms/L, P < 0.05), but not pulse frequency. Testosterone treatment resulted in a significant increase in 24-h mean serum GH (0.7 +/- 0.2 to 1.4 +/- 0.2 micrograms/L, P < 0.05), mean GH pulse amplitude (3.1 +/- 0.6 to 5.2 +/- 0.8 micrograms/L, P < 0.01) and serum IGF-I (0.9 +/- 0.1 to 1.1 +/- 0.1 U/mL, P < 0.05). In the normal men, tamoxifen significantly reduced 24-h mean serum GH (1.1 +/- 0.3 to 0.5 +/- 0.1 micrograms/L, P < 0.05), mean GH pulse amplitude (8.4 +/- 1.7 to 4.7 +/- 0.4 micrograms/L, P < 0.05), and serum IGF-I (1.0 +/- 0.1 to 0.7 +/- 0.1 U/mL, P < 0.001). In the hypogonadal men on testosterone replacement, tamoxifen lowered 24-h mean serum GH (1.3 +/- 0.2 to 0.6 +/- 0.2 micrograms/L, P < 0.01), mean GH pulse amplitude (5.5 +/- 1.0 to 2.4 +/- 0.8 micrograms/L, P < 0.01), and serum IGF-I (1.2 +/- 0.1 to 0.8 +/- 0.1 U/mL, P < 0.05). We conclude that testosterone plays an important role in the modulation of the male somatotropic axis in adulthood, as appears to be the case in puberty, and that this effect is partly dependent on the aromatization of testosterone to estradiol.

Adult↗
PubMed1993

A survey on orthodontics and the dental practitioner.

A questionnaire was mailed to locally trained Division One dental surgeons. The questionnaire was designed to assess the practice of orthodontics, the undergraduate orthodontic curriculum in relation to the dental practitioner and continuing orthodontic education. The results showed that the undergraduate orthodontic curriculum was of limited use to the practitioner and that there was a need for a continuing orthodontic education programme. Information pertaining to various aspects of orthodontic practice was presented.

Curriculum↗
PubMed1992

Impact of short-term estrogen administration on growth hormone secretion and action: distinct route-dependent effects on connective and bone tissue metabolism.

We recently reported that estrogen exerts distinct effects on the GH/IGF-1 axis that are dependent on the route of delivery, probably reflecting a first-pass effect on hepatic IGF-1 production. Oral administration reduces IGF-1 and increases GH levels; transdermal administration elevates IGF-1 without changing GH concentrations. Since mesenchymal tissue is a target for GH and IGF-1 action, we studied changes in the GH/IGF-1 axis following oral (ethinyl estradiol, 20 micrograms/day) versus transdermal (Estraderm 100 TTS, Ciba Geigy, 100 micrograms 17 beta-estradiol per day) estrogen delivery and compared corresponding effects on connective and bone tissue metabolism. Mean 24 h GH levels, IGF-1, markers of fibroblast (procollagen III) and osteoblast (procollagen I, osteocalcin) function, and indices of bone turnover (fasting urinary hydroxyproline and calcium to creatinine ratios, UOHPr/Cr and UCa/Cr) were measured before and after 2 months of either oral or transdermal therapy in two groups of postmenopausal women. Transdermal estrogen administration significantly (p less than 0.05) increased IGF-1, procollagen III, procollagen I, osteocalcin, and UOHPr/Cr. In contrast, oral estrogen administration had a suppressive effect; the levels of IGF-1 (p = 0.001), procollagen III (p = 0.018), procollagen I (p = 0.002), osteocalcin (p = 0.015), and UOHPr/Cr (p = 0.004) were significantly different from those measured during transdermal administration. Both treatments significantly reduced UCa/Cr (p less than 0.015). IGF-1 changes during estrogen therapy were significantly related (p less than 0.05) to changes in procollagen III, procollagen I, osteocalcin, and UOHPr/Cr. Transdermally delivered estrogen stimulates IGF-1 production, increases osteoblastic function, and stimulates bone and nonbone collagen synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1992

A specific stain for the detection of nonheme iron proteins in polyacrylamide gels.

Nonheme iron proteins can be visualized as blue bands in native polyacrylamide gels using a staining method that is both simple and rapid. The reaction of potassium ferricyanide with protein-bound iron atoms to form royal blue complexes occurs almost instantaneously and is sensitive enough to detect 1 microgram of analytical-grade ferritin and 2 micrograms of purified ferredoxin from cyanobacteria. No special treatment of reagents or apparatus was necessary. On comparison, this stain was found to be more specific than the Ferene S stain, not detecting bovine serum albumin even when present as a hundredfold excess over ferritin. The method was found to be effective for isoelectric focusing gels as well.

Animals↗
PubMed1992

Pyoderma gangrenosum, polycythemia rubra vera, and the development of leukemia.

A patient with long-standing, well-controlled polycythemia rubra vera developed recurrent episodes of bullous pyoderma gangrenosum followed by the transformation of his hematologic disease into a rapidly progressive acute myeloid leukemia. This case, together with previously described patients, indicates that the appearance of bullous pyoderma gangrenosum in a patient with polycythemia rubra vera is often of ominous prognostic significance.

Humans↗
PubMed1992

Soft-tissue cephalometric norms in Chinese adults with esthetic facial profiles.

Using a double selection process comprised of professional and lay judges, the cephalometric tracings on a final sample of 48 Chinese adults with esthetically pleasing profiles were analyzed. The soft-tissue cephalometric norms and standard deviations of two widely accepted soft-tissue analyses, the Legan and Burstone analysis and the Holdaway analysis, were determined. In comparison with white norms, the Chinese nose was less prominent (P < .01), the nasolabial angle was less obtuse (P < .01), both the upper and lower lips were more protrusive (P < .05), the upper lip curvature was greater (P < .01), and the soft-tissue chin thickness was less (P < .05). This variance between racial types emphasizes the need to recognize that soft-tissue lateral cephalometric norms are specific for the racial group and cannot always be applied across different racial types.

Adolescent↗
PubMed1992

Topical retinoic acid augments ultraviolet light-induced melanogenesis.

Melanin, the natural pigment found in human skin, absorbs and protects against the ultraviolet (UV) components of sunlight. Melanin production (melanogenesis) is increased by exposure to sunlight, causing a darker skin colour which is regarded as aesthetically pleasing by many humans, who therefore expose themselves to large amounts of potentially damaging sunlight. We have found that topically applied all-trans retinoic acid, a metabolic derivative of vitamin A, greatly enhances UV light-induced melanogenesis: the same preparation on its own had no effect on skin pigmentation. An orally administered retinoid, temarotene, did not have this effect. These observations were made using a lightly pigmented mouse strain, HRA: Skh-2, and confirmed in 2 human volunteers. This is the first time that metabolic derivatives of vitamin A have been shown to augment UV light-induced melanogenesis, suggesting a role for vitamin A in this process.

Animals↗
PubMed1992

Sunscreens protect epidermal Langerhans cells and Thy-1+ cells but not local contact sensitization from the effects of ultraviolet light.

This study compares the ability of two commonly used sunscreens--octyl dimethyl para-aminobenzoate (Padimate O) and 2-ethylhexyl-p-methoxycinnamate (2-EHMC)--to protect Langerhans cells (LC), Thy-1+ dendritic epidermal cells (Thy-1+ dEC), and local contact sensitivity (CS) from the effects of ultraviolet (UV) light. Chronic exposure of mice 5 d per week for 4 weeks with an intermediate dose of solar-simulated sunlight from which any UVC had been filtered reduced the LC and Thy-1+ dEC density of murine epidermis. This irradiation procedure was designed to simulate closely the daily exposure of humans to sunlight. This effect on LC and Thy-1+ dEC occurred in both albino and pigmented mice that develop a tan during the irradiation procedure, indicating that a tan does not protect these cells from the effects of UV light. Sunscreen preparations with Padimate O and 2-EHMC, both of which also contained benzophenone-3, as well as Padimate O or 2-EHMC in organic solvent, inhibited UV light from depleting LC from the epidermis of both mouse strains. Padimate O and 2-EHMC in organic solvent were used to ensure that these were the active ingredients in the sunscreen preparations. In contrast to the effects on LC, Padimate O, but not 2-EHMC, protected Thy-1+ dEC from UV exposure in both mouse strains, but neither protected against the development of local immunosuppression using a contact sensitivity model. Thus, even in a mouse strain that is sensitive to UV-induced immunosuppression, local immunosuppression can occur in the presence of normal densities of LC and Thy-1+ dEC.

Animals↗
PubMed1992

Regulation of the skin immune system by retinoids during carcinogenesis.

One of the immunosuppressive effects of both ultraviolet (UV) light and chemical carcinogens is to deplete Langerhans cells (LC) from the epidermis, suggesting that these cells play an important role in inducing immune responses to developing tumors during the early phases of carcinogenesis. Retinoids such as all-trans-retinoic acid (RA) are natural or synthetic derivatives of vitamin A; RA binds to nuclear receptors in the skin, effecting transcription of a wide range of genes. Topical application of RA prevents the tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) from depleting the density of LC in murine epidermis. In contrast, topical RA did not itself alter the normal LC density. RA also inhibited the development of TPA-induced immunosuppression to a locally applied contact sensitizer. Topical RA also prevented UV light from reducing the density of both LC and Thy-1+ dendritic epidermal cells (Thy-1+ dEC). However, the RA treatment did not prevent local immunosuppression to the contact sensitizer from developing in response to UV irradiation. The reasons for this are unclear, however, it is possible that RA does not inhibit some other immunosuppressive effect of UV light. Temarotene, a recently developed synthetic retinoid also inhibited UV light from reducing the LC and Thy-1+ dEC density from murine epidermis. Thus part of the anti-carcinogenic activity of retinoids may be due to their ability to protect LC during the early stages of carcinogenesis.

Animals↗
PubMed1992

Impact of octreotide, a long-acting somatostatin analogue, on glucose tolerance and insulin sensitivity in acromegaly.

OBJECTIVE: We aimed to investigate the impact of a long-acting somatostatin analogue, octreotide, on glucose tolerance and on insulin sensitivity in acromegaly. DESIGN: We performed a non-randomized controlled trial. PATIENTS: Seven patients with active acromegaly were assessed before and during octreotide therapy given in a dose of 500 micrograms three times daily subcutaneously. MEASUREMENTS: The effects of octreotide on carbohydrate metabolism were assessed by performing a glucose tolerance test and a euglycaemic hyperinsulinaemic clamp. These latter tests were undertaken 8 hours after the last dose, allowing GH and glucagon to return to pretreatment levels during the study. RESULTS: Octreotide significantly reduced (P less than 0.05) mean +/- SEM 12-h GH (from 42 +/- 13 to 10 +/- 3 mIU/I) and IGF-I (from 4.2 +/- 0.5 to 2.1 +/- 0.5 U/ml) concentrations. Glucose tolerance was normalized in four of five patients with impaired glucose tolerance without a significant change in mean insulin concentrations. The improvement in fasting and mean blood glucose during glucose tolerance testing was dependent on the pretherapy blood glucose concentrations (r = -0.95, P = 0.002). The glucose infusion rate during the hyperinsulinaemic (5 U/h) clamp was significantly increased (P less than 0.05, 15.3 +/- 1.8 vs 24.2 +/- 5.4 mumol/kg min) following octreotide treatment. Insulin infusion during the glucose clamp completely suppressed hepatic glucose production during but not before octreotide treatment (7.9 +/- 2.4 vs 0.7 +/- 2.2 mumol/kg min, P = 0.02). Insulin-mediated stimulation of peripheral glucose uptake was unaffected by treatment. Mean GH and glucagon levels during both clamp studies were not significantly different. CONCLUSIONS: Octreotide improves whole body insulin sensitivity by an increased ability of insulin to suppress hepatic glucose production without affecting the substantial impairment of peripheral insulin action. Octreotide has beneficial effects on carbohydrate metabolism in acromegalic patients with glucose intolerance.

Acromegaly↗
PubMed1992

Familial non-diabetic necrobiosis lipoidica.

Necrobiosis lipoidica (NL) is a cutaneous disorder with distinctive clinical and morphologic characteristics. It is associated with diabetes mellitus in two thirds of cases. The aetiology and pathogenesis of NL are unknown but familial cases of NL seem to be extremely rare. We report the occurrence of NL in two sisters with normal glucose tolerance.

Biopsy↗
PubMed1992

Angiotensinogen secretion by single rat pituitary cells: detection by a reverse haemolytic plaque assay and cell identification by immunocytochemistry.

A reverse haemolytic plaque assay (RHPA) for angiotensinogen was developed in rat hepatoma H4 cells and applied to investigate the possible secretion of angiotensinogen from rat pituitary cells in primary culture. Over a 24-hour incubation period in Cunningham chambers plaques with a mean area of 2,800 +/- 430 and 590 +/- 220 microns2/plaque (SD, n = 6) formed around all viable H4 cells and 2.8 +/- 0.59% of viable pituitary cells respectively. As a positive control PRL secretion from lactotrophs was routinely checked by the RHPA and shown to form plaques with a mean area of 4,050 +/- 1,850 microns2/plaque after a 4-hour incubation. By comparing plaque size in H4 cells with angiotensinogen release in cell culture, as quantified by radioimmunoassay, the secretion rate of angiotensinogen from pituitary cells was calculated as 22 +/- 8 ng/10(6) cells/24 h. Plaque-forming cells consisted of two morphologically distinct populations; 78% being small cells (less than 6 microns diameter) containing little cytoplasm and 22% were large (greater than 9 microns diameter) cells with an abundant cytoplasm. Immunocytochemical staining of pituitary cells after formation of plaques with anti-angiotensinogen, anti-LH and anti-PRL antiserum showed that the large plaque-forming cells were gonadotrophs and none were lactotrophs. All plaque-forming cells stained for angiotensinogen but only 44% of the viable cells which stained for angiotensinogen actually formed plaques. The possibility that cellular angiotensinogen was imported from extracellular sources was investigated by incubation of pituitary cells with pure 125I-angiotensinogen for periods up to 24 h. No uptake of the radiolabelled protein was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗
PubMed1991

Characterization of a soluble inorganic pyrophosphatase from Microcystis aeruginosa and preparation of its antibody.

A soluble inorganic pyrophosphatase was isolated from a crude extract of Microcystis aeruginosa by adsorption chromatography. The enzyme was purified to homogeneity as judged by sodium dodecyl sulfate (SDS) and nondenaturing polyacrylamide gel electrophoresis and N-terminal amino acid analysis. The molecular mass was estimated to be 80 kDa by gel filtration chromatography, 87 kDa by nondenaturing polyacrylamide gel electrophoresis, and 28 kDa by SDS-polyacrylamide gel electrophoresis. The enzyme has an isoelectric point of 4.5, which is similar to the pI values reported for other soluble inorganic pyrophosphatases. The sequence of 29 N-terminal amino acids was determined; only 4 of these amino acids are identical to those in the sequence of Saccharomyces cerevisiae inorganic pyrophosphatase. M. aeruginosa inorganic pyrophosphatase is a Mg(2+)-dependent enzyme exhibiting a pH optimum of around 7.5. Its KM value for inorganic pyrophosphate was estimated to be 1.30 mM. A specific antibody was raised in chicken to M. aeruginosa inorganic pyrophosphatase. No immunological cross-reactivity was seen when Western blots of partially purified S. cerevisiae or Escherichia coli inorganic pyrophosphatase were probed with the antibody.

Amino Acid Sequence↗
PubMed1991

Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man.

We have examined the mechanisms underlying reduced circulating GH concentrations in the obese human. Computer-assisted (deconvolution) analysis was used to determine endogenous GH secretory and clearance rates quantitatively from entire 24-h plasma GH concentration profiles. These analyses revealed that the half-life (t 1/2) of endogenous GH was significantly shorter in obese (11.7 +/- 1.6 min) than in normal weight subjects (15.5 +/- 0.81 min; P less than 0.01). The accelerated blood disposal rate of GH was not due to decreased circulating concentrations of GH-binding protein, since the latter were similar in obese (25 +/- 1.0%) and normal weight (24 +/- 2.3%) men. However, obese men had significantly fewer GH secretory bursts (3.2 +/- 0.53 vs. 9.7 +/- 0.67/day; P less than 0.01). Among the rare GH secretory bursts that occurred in obese subjects, there were significantly prolonged mean intersecretory burst intervals (282 +/- 65 vs. 131 +/- 11 min; P less than 0.05). The resultant daily GH production rate in obese men was reduced to one fourth that in normal weight individuals. Both GH secretion rate and burst frequency were negatively correlated with the degree of obesity (ponderal index). The decreases in GH burst frequency and half-life were specific, since GH secretory pulse amplitude (maximal rate of GH release), the mass of GH released per burst, and the duration of computer-resolved GH secretory bursts were not different in obese and normal weight men. We conclude that obese men harbor a double defect in GH dynamics involving both GH secretion and clearance, and that the severity of the GH secretory deficiency is proportionate to the degree of obesity.

Adult↗