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Biomedical subjects

C S Chung

Publications and source records attributed to C S Chung.

At least 91 records · Page 5Linked to original sources

Purification and molecular properties of malate dehydrogenase from the marine diatom Nitzschia alba.

Malate dehydrogenase (EC 1.1.1.37) was purified to homogeneity from the marine diatom Nitzschia alba. The purification steps consisted of (NH4)2SO4 precipitation, ion-exchange chromatography, Blue Sepharose affinity chromatography and gel filtration. A typical procedure provided 685-fold purification with 58% yield. The Mr of the holoenzyme was estimated to be 322,000 by gel filtration and 316,000 by ultracentrifugation. The enzyme migrated as a single polypeptide spot on two-dimensional polyacrylamide-gel electrophoresis with an Mr of 38,500, suggesting that the holoenzyme consists of eight identical subunits. This is the first case where malate dehydrogenase has been shown to be a homo-octamer; malate dehydrogenases from other sources are predominantly homodimers, with two homotetramers reported so far. The amino acid composition of the enzyme was determined and the N-terminal sequence of the subunit polypeptide was found to be Arg-Lys-Val-Ala-Val-Met-Gly-Ala-Ala-Gly-Gly-Ile-Gly-Gln-Pro-Leu-Ser-Leu- Leu-Leu - Lys-Leu-Ser-Pro-Gln-Val-Thr-Glu-Leu-Ser-Lys-Tyr-. For the first 21 amino acid residues, near-identical sequences were reported for the enzymes isolated from pig heart, Escherichia coli, yeast and watermelon. Other physicochemical and catalytic properties, such as sedimentation coefficient, partial specific volume, Stokes radius, excitation and emission maxima, Michaelis constants, pH optima, pH stability range and activation energy, of this enzyme are also presented.

Amino Acid Sequence↗

Test of genetic heterogeneity of cleft lip with or without cleft palate as related to race and severity.

The question of possible heterogeneity among population groups and phenotypic groups on the role of major gene in the etiology of cleft lip with or without cleft palate [CL(P)] was examined using the uniformly collected data in Hawaii. Complex segregation analysis was used to analyze patterns of family resemblance under the mixed model incorporating the effects of major gene and multifactorial inheritance. Analysis of the entire data showed superior fit of the mixed model including the effects of both major gene and multifactorial inheritance over the model of major gene alone or multifactorial inheritance alone. No significant heterogeneity could be detected between the high-incidence group (Oriental or Japanese) and the low-incidence group (non-Oriental) in the underlying general model, although higher heritability was observed in general. When families were classified into "severe" and "mild" phenotypes based on cleft lip vs. cleft lip and palate or unilateral vs. bilateral cleft in the proband, no significant differences could be detected between the two types in the underlying genetic model.

Cleft Lip↗

Purothionin from wheat endosperm reversibly blocks myogenic differentiation of chick embryonic muscle cells in culture.

Purothionin from wheat endosperm is a cysteine-rich, basic polypeptide of about 5000 Da, which modifies membrane permeability of cultured mammalian cells. This peptide was found to block fusion of chick embryonic muscle cells in culture but allows proliferation and alignment. A purothionin concentration of 6 micrograms/ml (1.2 microM) was necessary for the complete prevention of myotube formation. Under similar conditions, incorporation of [35S]methionine occurred normally but the synthesis of muscle-specific proteins including creatine kinase and acetylcholine receptor was strongly inhibited. In addition, purothionin blocked the uptake of 86Rb+, immediately after its addition to the cultured myoblasts. No such effects were found with the purothionin chemically modified with acetic or succinic anhydride. Thus, the basic residues in purothionin appear to be associated with the inhibition of myogenic differentiation. These results suggest that purothionin exerts its regulatory effect on the transition from proliferative to differentiative myoblasts by interfering with membrane permeability or intercellular contact and recognition, which are necessary for the initiation of muscle differentiation.

Animals↗

Vertical and radial motions of the body during the take-off phase of high jumping.

By placing the muscles of the take-off leg in faster eccentric or slower concentric conditions, a high jumper can increase the ground reaction force and the height of the jump. Film analysis of seven high jumpers showed that the radial velocity of the center of mass with respect to the supporting foot was more negative or less positive than the vertical velocity throughout the take-off phase. This favored faster eccentric or slower concentric conditions of the leg muscles. The radial distance from the hip of the take-off leg to the center of mass (RG/H) first decreased by 0.030 m, due to negative radial motions of the arms and swinging leg. This contributed to a smaller negative radial velocity of the hip (VRH), and thus to slower eccentric conditions of the muscles of the take-off leg. Therefore, it may have helped to cushion the initial impact with the ground. Subsequently, RG/H increased by 0.120 m, due to positive radial velocities of the arms, the swinging leg, and the head and trunk. This contributed first to larger negative (and later to smaller positive) VRH values, and thus to faster eccentric and slower concentric conditions of the muscles of the take-off leg.

Biomechanical Phenomena↗

Pituitary porcine growth hormone (pGH) and a recombinant pGH analog stimulate pig growth performance in a similar manner.

This study was conducted to establish the extent to which different doses of pituitary porcine growth hormone (ppGH) increase pig growth performance. Pigs were treated daily for 11 wk with 0, 35 or 70 micrograms ppGH/kg BW. In addition, these effects were compared with those produced by treating pigs with 0, 35, 70 or 140 micrograms.kg BW-1.d-1 of a recombinantly derived analog of porcine growth hormone (rpGH). This analog lacks the first seven amino acids at the NH2 terminus. Growth rate was increased similarly by ppGH and rpGH (the maximal increase was 19%). Feed efficiency was improved by ppGH and rpGH (the maximal response was 25%). This improvement in feed efficiency was associated with a decrease in feed intake (17% with the largest dose of rpGH). Both ppGH and rpGH decreased adipose tissue growth and increased muscle mass. Carcass lipid was decreased by 68% in pigs treated with the largest dose of rpGH. The recombinant pGH analog appeared to be less potent than ppGH in decreasing adipose tissue growth rate. All other parameters measured, however, indicated that rpGH mimicked the biological effects of ppGH (including binding to pig liver membranes and induction of insulin-like growth factor I production). Sensory panel evaluations indicated that neither ppGH nor rpGH affected pork palatability. Larger doses of pGH (greater than 70 micrograms/kg BW) adversely affected pig mobility. This impairment in mobility appears to be due to osteochondrosis. Our findings establish that the rpGH analog is equipotent to ppGH in stimulating growth performance and that pigs can be treated without any significant adverse effects when they are treated with less than 70 micrograms of pGH.kg BW-1.d-1.

Animals↗

The role of major gene in clubfoot.

The roles of major gene and multifactorial inheritance in the etiology of clubfoot (talipes equinovarus) were studied using Caucasian clubfoot families ascertained in Indiana. The method of analysis used was complex segregation analysis under the mixed model, in which five genetic parameters were examined to test hypotheses on major gene by displacement (t), degree of dominance (d), gene frequency (q), transmission probability (tau2), and multifactorial inheritance by heritability (H). The analysis showed that the segregation pattern of clubfoot in these families is best explained by assuming the action of a major gene with additional contribution of multifactorial inheritance. The estimates of the parameters under the best-fitting model were d = .82, t = 4.69, q = .030, tau2 = .50, and H = .17.

Clubfoot↗

Congenital anomalies: mortality and morbidity, burden and classification.

This study has attempted to assess the burden imposed by congenital anomalies in terms of postnatal mortality and morbidity, which were in turn used to classify anomalies as severe and mild types. Factors studied were postnatal mortality through age 7 years and morbidity, as measured by neurologic and psychologic abnormalities, histories of major surgery, prolonged hospitalization, and chronic infections. The study was based on a prospective study of 52,332 liveborn singletons of the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke. In general, the highest degree of burden was observed in syndromes and sequences, followed by multiple and single major anomalies. The burden due to major abnormalities as measured by attributable risk ranged from 0.436 for prolonged hospitalization up to one year, to 0.010 for chronic infections in subjects 1-7 years of age. In terms of mortality, the total attributable risk was 0.164, and the mean potential years of life lost was 5,020 per 10,000 population, which is considerably greater than that reported in other studies. An index constructed from mortality, neurologic, psychologic, and surgical variables provides a reasonable and objective means for classifying anomalies into severe and mild types.

Anthropometry↗

A genetic analysis of clubfoot in Hawaii.

The roles of major genes and multifactorial inheritance in the etiology of clubfoot (talipes equinovarus) were investigated based on 365 nuclear families consisting of three major racial groups of Hawaiians, Caucasians, and Orientals in Hawaii. Complex segregation analysis was employed using the mixed model with four parameters: major gene displacement (t), degree of dominance (d), gene frequency (q), and heritability (H). Heterogeneity was evident among the racial groups in the pattern of segregation of clubfoot. The most plausible genetic model is the presence of major gene effects with the multifactorial component for the Hawaiian and Caucasian groups, whereas no major gene action is evident for the Oriental group.

Asian People↗

Genetic epidemiology of cleft lip with or without cleft palate in the population of Hawaii.

Orientals consisting of Japanese, Chinese, Koreans, and Filipinos are clearly at higher risk for cleft lip with or without cleft palate [CL(P)] than whites, Puerto Ricans, and Hawaiians/part-Hawaiians in Hawaii. Using the model of diallele cross, CL(P) incidences in incrosses and outcrosses involving 564,002 live births distributed among 669 mating types were analyzed to study the extent of major gene involvement in the difference in the two groups and to investigate maternal effect in the etiology of CL(P). CL(P) cases excluding syndrome cases were classified into two types: all CL(P) cases and CL(P) cases without additional malformations. For either type there was no evidence to suggest that simple major gene plays a dominant role in accounting for racial differences as measured by deviations from additivity in the hybrids. For CL(P) cases without additional defects, a negative "maternal effect" was detected in Filipinos such that higher risk for this racial group depends on when the father is Filipino. Implications of the findings are discussed.

Cleft Lip↗

Exogenous pituitary and recombinant growth hormones induce insulin and insulin-like growth factor 1 resistance in pig adipose tissue.

In the present study, pigs were treated daily for 7 days with exogenous porcine growth hormone (pGH; 70 micrograms/kg BW) in order to determine whether pGH induced insulin and insulin-like growth factor 1 (1GF-1) resistance in pig adipose tissue. In the first experiment, pituitary-derived pGH (ppGH) decreased basal and insulin-stimulated lipogenesis by 50%. Insulin sensitivity decreased more than 90% as the result of pGH treatment. Sensitivity and responsiveness to IGF-1 were decreased 50% by ppGH. In a second experiment, pigs were treated daily (70 micrograms/kg BW) with exogenous pituitary pGH (ppGH) or recombinant pGH (rpGH) for 7 days in order to determine if the effects of pGH were intrinsic properties of the hormone. Both rpGH and ppGH caused similar decreases in basal rates of lipogenesis, insulin- and IGF-1-stimulated lipogenesis, and insulin and IGF-1 responsiveness in pig adipose tissue. In summary, the decrease in adipose tissue growth of pigs treated chronically with pGH is due in large part to the suppression of fatty acid synthesis and a decrease in the ability of insulin to stimulate lipid synthesis in pig adipocytes. These responses are intrinsic properties of pGH since the effects of rpGH mimicked those of ppGH. The role and importance of a decrease in IGF-1 responsiveness remains to be resolved.

Adipose Tissue↗

Stimulation of pig growth performance by porcine growth hormone: determination of the dose-response relationship.

The present study was undertaken to determine the relationship between dose of porcine growth hormone (pGH) and growth performance of pigs. Porcine GH was administered daily for 35 d [buffer-injected control = (C); 10 micrograms/kg body weight (BW) = (L); 30 micrograms/kg BW = (M); 70 micrograms/kg BW = (H)] to barrows (initial wt = 50 kg). Growth rate was significantly increased by pGH (14% for H dose vs C). Feed efficiency was increased in a dose-related manner (L = 7%, M = 10%, H = 17%) by pGH. There was a concurrent change in carcass composition of pGH-treated pigs. The H dose of pGH decreased the percentage of carcass lipid by 25% (P less than .05). Muscle mass was significantly increased in H vs C pigs (31 vs 26 kg). Serum insulin-like growth factor 1 (IGF-1) concentration increased in a manner that was linearly related to the pGH dose (r = .87). No antibodies to pGH were detected in any of the pigs. In summary, these results extend our earlier findings that pGH increases growth performance markedly. Based on the present findings it appears that the maximally effective dose of pGH is greater than 70 micrograms.kg BW-1.d-1 since several indices of the growth-promoting and metabolic effects of pGH (% carcass protein, % carcass lipid and feed efficiency) had not plateaued.

Animals↗

Effects of interracial crosses on cephalometric measurements.

The effects of race and interracial crossing were examined on six cephalometric measurements among 9,912 schoolchildren in Hawaii. The measurements studied were face height, bizygomatic diameter, bigonial diameter, head breadth, head length, and cephalic index. Racial effects were studied in terms of general racial effect, maternal effect, and hybridity and recombination effects based on a model of diallel cross. Generally, Chinese, Japanese, Koreans, and Filipinos were characterized by longer lateral and smaller anterior-posterior dimensions relative to Caucasians. Maternal effects appeared to be present in the measures of lateral dimension. No clear effects of hybridity and recombination were seen except for bizygomatic diameter, which appears to behave as a partial dominant trait. The racial mean of bizygomatic diameter, or the ratio of this measure to head length, were found to have a relationship with the racial incidences of cleft lip with or without cleft palate.

Adolescent↗

Characterization of porcine growth hormone (pGH) binding to porcine liver microsomes: chronic administration of pGH induces pGH binding.

The effect that GH has on regulating GH binding to its receptors has not been resolved. This report describes the characterization of porcine (p) GH binding to pig liver membranes and clarifies the issue of regulation of GH binding by measuring pGH binding to liver membranes prepared from pigs treated daily for 35 days with different doses of pGH (0, 10, 30, or 70 micrograms/kg BW). Specific binding of [125I]pGH was dependent on time, pH, and membrane protein concentration. At 23 C, pGH binding reached a steady state after 24 h. Maximal pGH binding was observed at pH 7. Binding increased linearly as membrane protein concentration was increased from 150 to 450 micrograms/tube. Specificity studies indicated that the hepatic GH receptor was somatogenic, since porcine PRL poorly inhibited [125I] pGH binding (cross-reactivity, 0.1%). Treatment of microsomes from control pigs with 4 m MgCl2 to remove endogenously bound pGH did not affect pGH binding, whereas binding was significantly increased to microsomes from pGH-treated pigs. Binding of pGH increased in a linear manner with the dose of pGH given for 35 days (r = 0.79), thus establishing the inductive effect of chronic pGH administration on pGH binding in pig liver. GH binding was highly correlated with weight gain in pigs treated with pGH (r = 0.76). In addition, the serum insulin-like growth factor I (IGF-I) concentration was increased linearly (r = 0.87) by pGH. This increase in serum IGF-I was also highly correlated with the increase in pGH binding (r = 0.71). These results suggest that hepatic GH binding plays an important role in regulating pig growth, which may be mediated, in part, by an increase in hepatic IGF-I synthesis and secretion. The present report is also the first to establish that exogenous pGH induces pGH binding to pig hepatic GH receptors and to relate this increase in binding to an enhancement in pig growth.

Animals↗

Stimulation of pig growth performance by porcine growth hormone and growth hormone-releasing factor.

The current study was undertaken to determine the effects of human growth hormone-releasing factor [hpGRF-(1-44)-NH2] on growth performance in pigs and whether this response was comparable to exogenous porcine growth hormone (pGH) treatment. Preliminary studies were conducted to determine if GRF increased plasma GH concentration after iv and im injection and the nature of the dose response. Growth hormone-releasing factor stimulated the release of pGH in a dose-dependent fashion, although the individual responses varied widely among pigs. The results from the im study were used to determine the dose of GRF to use for a 30-d growth trial. Thirty-six Yorkshire-Duroc barrows (initial wt 50 kg) were randomly allotted to one of three experimental groups (C = control, GRF and pGH). Pigs were treated daily with 30 micrograms of GRF/kg body weight by im injection in the neck. Pigs treated with pGH were also given 30 micrograms/kg body weight by im injection. Growth rate was increased 10% by pGH vs C pigs (P less than .05). Growth rate was not affected by GRF; however, hot and chilled carcass weights were increased 5% vs C pigs (P less than .05). On an absolute basis, adipose tissue mass was unaffected by pGH or GRF. Carcass lipid (percent of soft-tissue mass) was decreased 13% by GRF (P less than .05) and 18% by pGH (P less than .05). Muscle mass was significantly increased by pGH but not by GRF. There was a trend for feed efficiency to be improved by GRF; however, this was not different from control pigs. In contrast, pGH increased feed efficiency 19% vs control pigs (P less than .05). Chronic administration of GRF increased anterior pituitary weight but did not affect pituitary GH content or concentration. When blood was taken 3 h post-injection, both GRF- and pGH-treated pigs had lower blood-urea nitrogen concentrations. Serum glucose was significantly elevated by both GRF and pGH treatment. This was associated with an elevation in serum insulin. These results indicate that increasing the GH concentration in blood by either exogenous GH or GRF enhances growth performance. The effects of pGH were more marked than for GRF. Further studies are needed to determine the optimal dose of GRF to administer in growth trials and the appropriate pattern of GRF administration in order to determine whether GRF will enhance pig growth performance to the extent that exogenous pGH does.

Animals↗

Segregation analysis of cleft lip with or without cleft palate: a comparison of Danish and Japanese data.

The genetic basis of cleft lip with or without cleft palate [CL(P)] remains unresolved. The controversy on the role of a major gene is confounded with possible population differences. This study examines the issue of population differences by comparing two contrasting populations: Caucasians and Japanese. Japanese are known to have higher population incidence of CL(P) and yet lower recurrence risks among relatives. The study subjects consist of 2,998 nuclear families of the Danish population and 627 families of the Japanese population. The uniformly coded data were subjected to complex segregation analysis based on the mixed model. The analysis has revealed that the Danish data can be best explained by a combination of major gene action and multifactorial inheritance. The best-fitting model is characterized by recessive gene with displacement effect (t) of 2.7 in the standardized unit and gene frequency of .035. The heritability is estimated as .97. The transmission probability of Aa----a for the major gene is consistent with 1/2. On the contrary, the Japanese data can be best accounted for only by multifactorial inheritance with the heritability estimate of .77. No major heterogeneity could be detected between subsets of the data within the populations as grouped by types of ascertainment or mating. It is thus concluded that the observed inconsistency between the two populations is explained by a significant role of major gene in the Caucasian population, but not in the Japanese population.

Abnormalities, Multiple↗

Stimulation of swine growth by porcine growth hormone.

Highly purified porcine growth hormone (pGH; USDA-B1) was administered by im injection (22 micrograms X kg body weight-1 X d-1) to rapidly growing Yorkshire barrows for 30 d. Growth hormone significantly increased growth rate (10%), feed efficiency (4%), cartilage growth and muscle mass. However, pGH did not affect carcass adipose tissue mass. Intramuscular lipid content of the longissimus was increased 50% by pGH administration. Plasma pGH concentration was elevated (7- to 11-fold) for 3 to 5 h post-injection. Chronic administration of pGH depressed pituitary GH content and concentration approximately 45%. No GH antibodies were detected in the plasma of GH-treated swine. Plasma somatomedin-C concentration was increased 55% by GH treatment 3 h post-injection. Plasma glucose and insulin concentrations were both significantly increased in GH-treated swine, suggesting that the animals had developed a state of insulin resistance. Plasma-free fatty acid concentration tended to be higher in GH-treated animals. Treatment of swine with pGH significantly decreased plasma blood urea nitrogen. Assessment of animal health during the trial and postmortem indicated that pGH administration did not have any adverse effects. In summary, treatment of young, rapidly growing swine with pGH stimulated growth performance without affecting animal health or inducing the production of GH antibodies.

Animals↗