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Biomedical subjects

S W Yang

Publications and source records attributed to S W Yang.

68 records · Page 4Linked to original sources

Role of selected endogenous peptides in growth hormone-releasing hexapeptide activity: analysis of growth hormone-releasing hormone, thyroid hormone-releasing hormone, and gonadotropin-releasing hormone.

The purpose of this study was to evaluate the contribution of endogenous GH-releasing hormone (GHRH) to exogenous GH-releasing hexapeptide (GHRP-6) activity, and to determine whether TRH or GnRH are endogenous analogs of GHRP-6. The activity of GHRP-6, a synthetic GH secretagogue, was significantly attenuated in rats administered GHRH antiserum or alpha-methyl-rho-tyrosine to reduce endogenous GHRH concentrations, and also in rats administered 5-50 micrograms/kg of [N-Ac-Tyr1,D-Arg2]-GRF 1-29 amide to block pituitary GHRH receptors. However, GHRP-6 activity was potentiated in rats administered 150 micrograms/kg [N-Ac-Tyr1,D-Arg2]-GRF 1-29 amide, presumably due to partial agonist activity of the GHRH receptor antagonist at the higher dose. These data show that endogenous GHRH contributes to full expression of exogenous GHRP-6 activity in vivo. Like TRH, a subthreshold dose of GHRP-6 was significantly more effective in hypothyroid rats than in euthyroid rats. However, suprathreshold doses of GHRP-6 were less effective in hypothyroid rats. Unlike TRH, GHRP-6 had no effect on GH and prolactin release from GH3 cells, and TRH and GnRH were poor competitors for 3H-GHRP-6 binding sites on pituitary membranes. A GnRH receptor antagonist did not block GHRP-6 activity in vivo, and GnRH administered alone or in combination with GHRP-6, did not stimulate GH release. The results of this study suggest that synergy between GHRH and GHRP-6 seen in pharmacological studies is physiologically relevant, and that TRH and GnRH are not endogenous analogs of GHRP-6.

Animals↗

Effects of coadministered growth hormone (GH)-releasing hormone and GH-releasing hexapeptide on maladaptive aspects of obesity in Zucker rats.

The purpose of this study was to determine the effect of chronic pharmacological stimulation of the pituitary gland on GH hyposecretion and other maladaptive aspects of obesity. Obese Zucker rats were coadministered GH-releasing hormone (GHRH; 3 micrograms/kg) and GH-releasing hexapeptide (GHRP-6; 300 micrograms/kg), a potent combination of synergistic GH secretagogues, once daily for 60 consecutive days. Although pituitary weights and GH concentrations were higher in obese rats administered the peptides than in obese rats administered saline, stimulated GH secretion was lower in obese rats than in lean rats. However, compared to those in lean rats, plasma insulin-like growth factor-I and insulin concentrations were higher in the obese rats regardless of treatment. The GH secretagogues did not alter food intake or body weight gain in sexually mature obese rats, whereas body weight gain was significantly increased when they were administered to prepubertal obese rats. Although glucose tolerance was impaired in both groups of obese rats, it improved in obese rats administered GHRH and GHRP-6 compared to that in obese rats administered saline. On the other hand, plasma cholesterol concentrations were elevated in obese rats administered the GH secretagogues but not saline. In conclusion, the results of this study suggest that hyposensitivity to GHRH and GHRP-6 in obese Zucker rats results from high concentrations of plasma insulin-like growth factor-I that negatively feedback on stimulated GH secretion. Nonetheless, daily episodes of endogenous GH secretion resulting from chronic coadministration of GH secretagogues significantly influenced the pituitary gland as well as lipid and carbohydrate metabolism.

Animals↗

Robust growth hormone (GH) secretion in aged female rats co-administered GH-releasing hexapeptide (GHRP-6) and GH-releasing hormone (GHRH).

Aging is associated with a blunted growth hormone (GH) secretory response to GH-releasing hormone (GHRH), in vivo. The objective of the present study was to assess the effects of aging on the GH secretory response to GH-releasing hexapeptide (GHRP-6), a synthetic GH secretagogue. GHRP-6 (30 micrograms/kg) was administered alone or in combination with GHRH (2 micrograms/kg) to anesthetized female Fischer 344 rats, 3 or 19 months of age. The peptides were co-administered to determine the effect of aging upon the potentiating effect of GHRP-6 on GHRH activity. The increase in plasma GH as a function of time following administration of GHRP-6 was lower (p less than 0.001) in old rats than in young rats; whereas the increase in plasma GH secretion as a function of time following co-administration of GHRP-6 and GHRH was higher (p less than 0.001) in old rats than in young rats (mean Cmax = 8539 +/- 790.6 micrograms/l vs. 2970 +/- 866 micrograms/l, respectively; p less than 0.01). Since pituitary GH concentrations in old rats were lower than in young rats (257.0 +/- 59.8 micrograms/mg wet wt. vs. 639.7 +/- 149.2 micrograms/mg wet wt., respectively; p less than 0.03), the results suggested that GH functional reserve in old female rats was not linked to pituitary GH concentration. The differential responses of old rats to individually administered and co-administered GHRP-6 are important because they demonstrate that robust and immediate GH secretion can occur in old rats that are appropriately stimulated. The data further suggest that the cellular processes subserving GH secretion are intact in old rats, and that age-related decrements in GH secretion result from inadequate stimulation, rather than to maladaptive changes in the mechanism of GH release.

Aging↗

Finite-element modeling of the synthetic intervertebral disc.

An ideal and realistic finite-element analysis should include several factors, such as geometry (shape and size), the relative volumes of the nucleus to the anulus fibrosus, the fiber volume fraction within the anulus, and material properties. In this study, a finite-element analysis model for the disc that included these factors was developed. In addition, synthetic disc prostheses with the same specifications of geometry and material properties were manufactured. The developed model was found to be reliable and accurate when finite-element analysis results were compared with experimental synthetic disc data. The model also matched the mechanical behavior of the natural disc. This finite-element analysis model provides a tool to study the mechanical behavior of discs with varying degrees and types of injury and degeneration.

Biomechanical Phenomena↗

[A study on BrdU labelling index of gastric cancer using in vitro labelling method].

In order to reveal the effect of environmental factors to BromodeoxyUridine labelling index (BrdU L.I.) and its usefulness as clinicopathological information, 522 specimens obtained from 121 lesions of gastric cancer were studied. Five hundred twenty two specimens in which BrdU had been incorporated using an in vitro labelling method were divided into 3 groups according to their degree of necrosis and cell infiltration. The average L.I. of the specimens with no or slight necrosis was 23.3 +/- 8.7%, medium, 14.2 +/- 10.0%, and severe necrosis, 6.6 +/- 3.8%, with no or slight cell infiltration, 25.3 +/- 9.5%, medium, 21.0 +/- 7.1%, and severe cell infiltration, 21.2 +/- 6.1%, therefore L.I. correlated to necrosis and cell infiltration. Representative values for each lesion were adopted and compared using 3 methods. In method A, a representative value of the L.I. for each lesion was chosen using all biopsy specimens, method B using specimens without necrosis, and method C, specimens without necrosis and cell infiltration. L.I. correlated to stage and the lymphnode metastasis only using methods, B and C and more strictly using method C. Necrosis and cell infiltration should be considered in adopting a representative value of the L.I. for each lesion. Method C is considered to be a best among the three studied, and the L.I. of gastric cancer may be considered a clinicopathological marker.

Biopsy↗

Fingerprinting of near-homogeneous DNA ligase I and II from human cells. Similarity of their AMP-binding domains.

DNA ligases play obligatory roles during replication, repair, and recombination. Multiple forms of DNA ligase have been reported in mammalian cells including DNA ligase I, the high molecular mass species which functions during replication, and DNA ligase II, the low molecular mass species which is associated with repair. In addition, alterations in DNA ligase activities have been reported in acute lymphocytic leukemia cells, Bloom's syndrome cells, and cells undergoing differentiation and development. To better distinguish the biochemical and molecular properties of the various DNA ligases from human cells, we have developed a method of purifying multiple species of DNA ligase from HeLa cells by chromatography through DEAE-Bio-Gel, CM-Bio-Gel, hydroxylapatite, Sephacryl S-300, Mono P, and DNA-cellulose. DNA-cellulose chromatography of the partially purified enzymes resolved multiple species of DNA ligase after labeling the enzyme with [alpha-32P]ATP to form the ligase-[32P]AMP adduct. The early eluting enzyme activity (0.25 M NaCl) contained a major 67-kDa-labeled protein, while the late eluting activity (0.48 M NaCl) contained two major labeled proteins of 90 and 78 kDa. Neutralization experiments with antiligase I antibodies indicated that the early and late eluting activity peaks were DNA ligase II and I, respectively. The three major ligase-[32P]AMP polypeptides (90, 78, and 67 kDa) were subsequently purified to near homogeneity by elution from preparative sodium dodecyl sulfate-polyacrylamide gels. All three polypeptides retained DNA ligase activities after gel elution and renaturation. To further reveal the relationship between these enzymes, partial digestion by V8-protease was performed. All three purified polypeptides gave rise to a common 22-kDa-labeled fragment for their AMP-binding domains, indicating that the catalytic sites of ligase I and II are quite similar, if not identical. Similar findings were obtained from the two-dimensional gel electrophoresis of their AMP-binding domains in the trypsin-digested protein fragments. The results also suggested that these isozymes have been derived from the same primordial DNA sequence or from the same precursor protein. The purification scheme and the data obtained will be instrumental for the further elucidation of the biological roles of various DNA ligases from human cells.

Adenosine Monophosphate↗

A study on nesidioblastosis in hyperinsulinemic hypoglycemia--diagnosis, treatment, and neurologic sequelae.

The medical records of six cases of nesidioblastosis were examined to determine the diagnostic approach, treatment, and neurologic sequelae. All six patients were male, and their ages at the onset of the disease ranged from one day to six months (mean 3.36 +/- 2.5 mo.). Initial clinical features were seizure, cyanosis, poor feeding, and apnea. Other subsequent symptoms were developmental delay, hyperactivity, and cold sweating. The Birth weight of the neonatal onset group was heavier than the postneonatal onset group (4.4 +/- 0.3 vs 3.26 +/- 0.04 kg). Before the diagnosis of hyperinsulinism, steroids of ACTH proved effective for seizure control. Initially, hyperinsulinemia (serum insulin greater than 10 microU/ml) was detected in four cases, but another two cases also showed hyperinsulinism by insulin/glucose(I/G) ratio greater than 0.3 during the fasting test. The glucagon response performed in 2 cases, showed normal and partial responses. Euglycemia was obtained by near total pancreatectomy (95% pancreatic resection)without malabsorption or persistent diabetes. In one case, nesidioblastoma coexisted with nesidioblastosis. Developmental delay was noted in three cases. In this group, the mean duration between symptom onset and operation was longer than the group without developmental delay (1.25 +/- 0.47 vs 0.38 +/- 0.19 yr).

Brain Damage, Chronic↗

Pathologic findings after recession and resection of extraocular muscles in rabbits.

A study on the pathologic findings after recession and resection of extraocular muscles in rabbits was performed. Fibrosis of the extraocular muscles increased with time, which showed no difference between the recessed and resected muscles. Inflammation and foreign body reaction decreased with time, which showed no difference between the recessed and resected muscles. Adhesions of extraocular muscles to the sclera were observed from one month after the operation. The resected muscles showed milder adhesion to the sclera than the recessed ones. The operated extraocular muscles showed atrophies at one month, which showed no difference between the recessed and resected muscles. According to our results, when reoperation is needed, fibrosis of the extraocular muscles after recession and resection should be considered when making a decision on the amount of muscle to be recessed and resected.

Animals↗

Biomechanics of lumbosacral spinal fusion in combined compression-torsion loads.

The current study investigates the stabilizing effects of three different types of spinal fusion to the juxta-free motion segments and to the fused segment of the lumbosacral spine under combined compression-torsion loads. Sixteen fresh human cadaver lumbosacral spines were tested under a simulated physiologic loading condition. The relative movements of the motion segments, as well as the angular rotations and the center of rotation were then computed and analyzed. The average torsional stiffness of the unfused three-motion segment was found to be 2.35 nm/degree. After fusion, the torsional stiffness did not increase significantly. Under the compression-torsional load, the anterior and bilateral-lateral fusions provided adequate stabilizing effect on the fused segment. The posterior fusion provided the least amount of stabilizing effect. These findings are similar to the results of the compression-bending experiment. Whereas the compression-bending loads produced significantly increased stress at the juxta-free segments, the compression-torsional loads did not produce any significant amount of increase in torsional stress at the juxta-free segments.

Biomechanical Phenomena↗

Diagnosis of gastric adenoma versus early gastric cancer by bromodeoxyuridine immunohistochemistry from gastric biopsy specimen.

Differentiation between gastric adenomas and type IIa early gastric cancer by macroscopic and histologic examinations is often difficult. This study has shown that there are differences in the distribution of S-phase cells in these two types of tumour, and these differences can be exploited to differentiate between them. The distribution of S-phase cells was assessed by Bromodeoxyuridine (BrdU) immunohistochemistry using an in vitro BrdU-labelling method. Biopsy specimens were obtained from 27 lesions (12 adenomas and 15 type IIa early gastric cancers), and the distributions of BrdU-labelled cells in the tumour thickness as well as in the superficial layer of the tumour were determined. Significant difference was seen in the labelling of the two tumour types with regard to both these parameters. Using the criteria of BrdU immunohistochemistry, the accuracy of differentiation between gastric adenomas and cancers was 88.9%. Therefore, it is concluded in this study that in vitro BrdU labelling is a useful method of diagnosing gastric adenomas and cancers.

Adenoma↗

Effect of bradykinin on cultured bovine corneal endothelial cells.

PURPOSE: To clarify the effect of bradykinin on cytosolic free calcium mobilization and cell proliferation in cultured bovine corneal endothelial cells (BCEC). METHODS: The cytosolic free calcium concentration (Ca2+]i) was measured with the InCa(TM) Imaging System after the treatment of bradykinin (10(-11) to 10(-7) M) alone or with the pretreatments of EGTA, bradykinin receptor (Bk1 and Bk2) antagonists and an inhibition of phospholipase C (U-73122). Also, the effect of bradykinin on cell proliferation in BCEC was evaluated using cell counts. RESULTS: In BCEC, [Ca2+]i in the resting state was 87 +/- 9 nM. Bradykinin induced an increment of [Ca2+]i in a concentration-dependent manner and its 50% effective concentration was approximately 5 x 10(-11) M. A [Ca2+]i increment at 10(-8) M bradykinin was inhibited with the pretreatment of EGTA, an extracellular calcium chelator. U-73122 (5 x 10(-6) M) attenuated the bradykinin-induced [Ca2+]i increment. The pretreatment of HOE-140 (Bk2 antagonist) almost attenuated the bradykinin (10(-8) M)-induced [Ca2+]i increase, but des-Arg9-[Leu(8)]-bradykinin (Bk1 antagonist) did not suppress it. To investigate the physiological effect of bradykinin, the effect of bradykinin on cell proliferation was studied. 10(-8) M of bradykinin produced a significant increase in cell numbers. This mitogenic effect of bradykinin was inhibited by the Bk2 antagonist. CONCLUSIONS: Bradykinin-induced stimulation of the signal transduction pathway in BCEC is coupled with the Bk2 type receptor. Furthermore, bradykinin produces the mitogenic effect in BCEC.

Animals↗