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C B Chan

Publications and source records attributed to C B Chan.

53 records · Page 3Linked to original sources
PubMed1988

Role of the cholinergic nervous system in acid secretion.

Stimulation of acid secretion by muscarinic agents involves receptors with a higher apparent affinity to the M1-antagonists, pirenzepine and telenzepine, than those regulating heart rate and salivary secretion. However, the localization of the proposed M1-receptors regulating acid secretion remains unclear. Studies with parietal cells isolated from several species indicate that parietal cells have a muscarinic receptor with low affinity for the M1-antagonists. Our studies with somatostatin cells isolated from canine fundic mucosa indicates that the muscarinic receptor inhibiting somatostatin release also is of low affinity for M1-antagonists. We have found no evidence for regulation of histamine release from canine fundic mast cells, whereas there is evidence that acetylcholine induces histamine release from the enterochromaffin-like cells of the rat and rabbit fundic mucosa. Further studies will be necessary to determine which of the muscarinic receptors potentially involved in the regulation of acid secretion is responsible for the M1-behavior of this pathway.

Animals↗
PubMed1987

Further evidence for genetic heterogeneity in the fragile X syndrome.

The X-linked fragile X [fra(X)] syndrome, associated with a fragile site at Xq27.3, is the most common Mendelian inherited form of mental deficiency. Approximately 1 in 1060 males and 1 in 677 females carry the fra(X) chromosome. However, diagnosis of carrier status can be difficult since about 20% of males and 44% of females are nonpenetrant for mental impairment and/or expression of fra(X). We analyzed DNA from 327 individuals in 23 families segregating fra(X) for linkage to three flanking polymorphic probes: 52A, F9, and ST14. This allowed probable nonpenetrant, transmitting males and carrier females to be identified. A combined linkage analysis was conducted using these families and published probe information on F9 in 27 other families, 52A in six families, and ST14 in five families. The two-point recombination fraction for 52A-F9 was 0.13 (90% confidence interval, 0.10-0.16), for F9-fra(X) was 0.21 (0.17-0.24), and for fra(X)-ST14 was 0.12 (0.07-0.17). Tight linkage between F9 and fra(X) was observed in some families; in others loose linkage was seen suggesting genetic linkage heterogeneity. Risk analysis of carrier status using flanking DNA probes showed that probable nonpenetrant transmitting males were included in families showing both tight and loose linkage. Thus, in contrast to our previous conclusions, it appears that the presence or absence of nonpenetrant, transmitting males in a family is not an indicator of heterogeneity. To determine if heterogeneity was present, we employed the admixture test. Evidence for linkage heterogeneity between F9 and fra(X) was found, significant at P less than 0.0005. Nonsignificant heterogeneity was seen for 52A-F9 linkage. No heterogeneity was found for fra(X)-ST14. The frequency of fra(X) expression was significantly lower in families with tight F9-fra(X) linkage than in families with loose linkage. Cognition appeared to relate to linkage type: affected males in tight linkage families had higher IQs than those in loose linkage families. These findings of genetic heterogeneity can account in part for the high prevalence and apparent high new mutation rate of fra(X). They will affect genetic counseling using RFLPs. An understanding of the basis for genetic heterogeneity in fra(X) will help to clarify the nature of the unusual pattern of inheritance seen in this syndrome.

Fragile X Syndrome↗
PubMed1987

The effect of jejunoileal bypass (JIB) in the obese Zucker rat on a sub-group of enteroendocrine cells.

The effect of jejunoileal bypass in lean and obese Zucker rats on a number of enteroendocrine cell types was investigated 5 weeks following surgery to remove 80 percent of the small bowel from continuity. The endocrine cells containing somatostatin, cholecystokinin, gastric inhibitory polypeptide, enteroglucagon and neurotensin were investigated. In control rats enteroglucagon cell number was decreased in obese compared to lean animals (5 +/- 1 vs 11 +/- 1 cells/mm). Following jejunoileal bypass the enteroglucagon cell population increased two-fold in both the functional and bypassed bowel in obese rats but was not elevated in lean animals. A significant increase in the number of cholecystokinin cells in the bypassed loop of the jejunum in both lean and obese bypassed rats was observed. The cholecystokinin cell population was also markedly elevated in the functional jejunum of obese but not lean bypassed rats. Only small changes were noted in cell numbers of gastric inhibitory polypeptide, somatostatin and neurotensin containing cells, suggesting that individual cell types have specific stimuli for proliferation. Epithelial height, a measure of intestinal adaptation, was similar in lean and obese rats in both the control and bypassed states, but weight loss in obese bypassed animals was significantly greater than that of lean bypassed rats. The hyperinsulinemia of obese rats was only partially normalized by jejunoileal bypass. These data indicate that jejunoileal bypass has effects on specific enteroendocrine cells which differ between lean and obese Zucker rats, and between individual cell types.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Genetics and expression of the fragile X syndrome.

The discovery of the Fragile X (fra(X] syndrome represents a major advance in our understanding of mild mental retardation. This X-linked syndrome is the most common hereditary form of mental retardation. Recent estimates find that approximately 1/981 males and 1/677 females carry the fra(X) chromosome. The majority of affected males are moderate to severely retarded, but about 20% are mildly retarded and about 5% are borderline. Approximately 20% of males who inherit the fra(X) chromosome are termed non-penetrant; they do not express it cytogenetically and are of normal intellect. About 1/3 of carrier females show mental impairment and about 10% are mildly retarded. We have found evidence for genetic heterogeneity based on linkage analysis to flanking DNA probes. Some large families show tight linkage between fra(X) and the flanking probe F9, while others show loose linkage. Preliminary findings indicate the linkage heterogeneity may also be related to cognition: affected males in tightly linked families tended to be mildly retarded.

Cognition Disorders↗
PubMed1985

Genetic linkage heterogeneity in the fragile X syndrome.

Genetic linkage between a factor IX DNA restriction fragment length polymorphism (RFLP) and the fragile X chromosome marker was analyzed in eight fragile X pedigrees and compared to eight previously reported pedigrees. A large pedigree with apparently full penetrance in all male members showed a high frequency of recombination. A lod score of -7.39 at theta = 0 and a maximum score of 0.26 at theta = 0.32 were calculated. A second large pedigree with a nonpenetrant male showed tight linkage with a maximum lod score of 3.13 at theta = 0, a result similar to one large pedigree with a nonpenetrant male previously reported. The differences in lod scores seen in these large pedigrees suggested there was genetic heterogeneity in linkage between families which appeared to relate to the presence of nonpenetrant males. The combined lod score for the three pedigrees with nonpenetrant males was 6.84 at theta = 0. For the 13 other pedigrees without nonpenetrant males the combined lod score was -21.81 at theta = 0, with a peak of 0.98 at theta = 0.28. When lod scores from all 16 families were combined, the value was -15.14 at theta = 0 and the overall maximum was 5.13 at theta = 0.17. To determine whether genetic heterogeneity was present, three statistical tests for heterogeneity were employed. First, a "predivided-sample" test was used. The 16 pedigrees were divided into two classes, NP and P, based upon whether or not any nonpenetrant males were detected in the pedigree. This test gave evidence for significant genetic heterogeneity whether the three large pedigrees with seven or more informative males (P less than 0.005), the eight pedigrees with three informative males (P less than 0.001), or all 16 pedigrees (P less than 0.001) were included in the analysis. Second, Morton's large sample test was employed. Significant heterogeneity was present when the analysis was restricted to the three large pedigrees (P less than 0.025), or to the eight pedigrees with informative males (P less than 0.05) but not when smaller, less informative pedigrees were also included. Third, an "admixture" test for heterogeneity was employed which tests for linkage versus no linkage. A trend toward significance was seen (0.05 less than P less than 0.10) which increased when the analysis was restricted to the larger, more informative pedigrees.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

The effect of total parenteral nutrition (TPN) on the enteroinsular axis in the rat.

The effect of 6 days of total parenteral nutrition (TPN) on the enteroinsular axis was studied in vivo and in vitro in the rat. During the TPN period, blood samples were taken from control and TPN animals to determine the comparative pattern of GIP release. Glucose, insulin and GIP responses to oral glucose (OGTT) were compared in TPN and control rats. The effect of glucose and GIP on insulin release from the isolated perfused pancreas of the same animals was investigated to determine if TPN altered the sensitivity of the beta cell. In conjunction with these studies the number and distribution of GIP-containing cells were compared in control and TPN animals. TPN resulted in no change in basal levels of glucose, insulin and IR-GIP. An exaggerated insulin response to OGTT occurred after TPN whereas the glucose response was reduced. The IR-GIP response to glucose was normal following TPN. The isolated perfused pancreas showed a 30% increase in insulin release in response to GIP after TPN. The insulin response to glucose appeared normal as did the number and distribution of GIP cells. Fluctuations in GIP and insulin levels in control animals were diurnal in nature, whereas IR-GIP levels in TPN animals remained near fasting levels. It was hypothesized that the increase in beta cell sensitivity to GIP may be causally connected to the exposure of the pancreas to chronically low levels of GIP during TPN.

Animals↗
PubMed1985

Gastric inhibitory polypeptide and hyperinsulinemia in the Zucker (fa/fa) rat: a developmental study.

The role of the gut hormone GIP (gastric inhibitory polypeptide; glucose-dependent insulinotropic polypeptide) in the development of hyperinsulinemia of pre-obese (fa/fa) Zucker rats was investigated. Plasma GIP levels were compared in lean and fa/fa pups from 21 to 35 days of age. The onset of both basal and glucose-stimulated hyperinsulinemia was studied. Possible causal roles for glucose, GIP and acetylcholine in hyperinsulinemia were investigated in the isolated perfused pancreas preparation. Immunocytochemical studies of pancreatic islets were also carried out. Glucose-stimulated hyperinsulinemia was present in fa/fa rats at 21 days of age but fasting hyperinsulinemia did not become apparent until 35 days of age. At no time did plasma GIP levels differ between lean and fa/fa rats. Immunocytochemical analysis of the pancreas revealed enlarged islets in fa/fa rats from 7 days of age onward. In the in vitro perfused pancreas of 21 day old fa/fa pups the insulin response was not different from that of lean controls in the presence of glucose (300 mg/dl) plus GIP or acetylcholine. An increased pancreatic insulin response to glucose (300 mg/dl or 80 mg/dl) plus GIP in fa/fa compared to lean animals was observed at 35 days of age. These data suggest that defects in the beta-cell response to GIP become apparent at 35 days of age in fa/fa rats resulting in a loss of the glucose threshold for the insulinotropic action of GIP and onset of fasting hyperinsulinemia in vivo. Causal factors for glucose-stimulated hyperinsulinemia at 21 days of age appear to be complex and not easily replicated in in vitro experiments.

Age Factors↗
PubMed1984

Gastric inhibitory polypeptide (GIP) and insulin release in the obese Zucker rat.

The involvement of the gut hormone GIP (gastric inhibitory polypeptide, glucose-dependent insulinotropic polypeptide) in the hyperinsulinemia of the adult obese Zucker rat was investigated. Glucose, insulin, and GIP responses to oral glucose were compared in lean and obese rats. The sensitivity of the isolated, perfused pancreas to glucose and GIP was studied in basal and hyperglycemic conditions in lean and obese rats. Immunocytochemical studies of the gut and pancreas were also carried out. The glucose and GIP responses to oral glucose were similar in lean and obese rats, but obese animals were hyperinsulinemic compared with lean controls under fasting conditions and after oral glucose. The isolated, perfused pancreas of obese Zucker rats had an elevated insulin response to 300 mg/dl glucose. GIP increased the insulin response to 300 mg/dl glucose threefold in both lean and obese rats. At basal glucose levels (80 mg/dl), GIP augmented insulin release in obese but not in lean rats. Immunocytochemical studies demonstrated the presence of enlarged islets in obese rats due to an increase in the B-cell mass. A-, D-, and PP-cells appeared normal. Obese and lean rats had similar numbers of GIP-containing cells in the gut. This study suggests that GIP may contribute to the fasting hyperinsulinemia characteristic of adult obese Zucker rats. GIP infusion to achieve levels equivalent to those seen in the basal state are capable of stimulating insulin release in the absence of hyperglycemia in the obese rat, which suggests an impairment of the regulatory mechanisms controlling the glucose-dependent insulinotropic action of GIP in these animals.

Animals↗
PubMed1983

The effect of massive small bowel resection (MSBR) and small intestinal bypass (JIB) in the rat on the enteroinsular axis.

The effect of massive small bowel resection (MSBR) and jejuno-ileal bypass (JIB) on the enteroinsular axis in rats was compared. Glucose levels after an oral glucose tolerance test were determined in MSBR, JIB and control animals. The response of the beta-cell mass to glucose and gastric inhibitory polypeptide (GIP) was established in the same animals using the isolated perfused pancreas model. Immunocytochemical and morphological studies were performed to monitor the adaptive changes seen in the intestine of these animals. The glucose response to the oral glucose load was blunted in both test groups with the fasting GIP levels in the JIB group being elevated and the MSBR group being reduced. The response of the isolated perfused pancreas to GIP showed a marked (70%) reduction of insulin release in the JIB rats and a slight but non-significant reduction in the MSBR rats. In both groups the insulin response to glucose alone appeared normal. The area of the pancreatic islets and the percentage of the total area consisting of the four islet cell types (B, A, D, PP) were unchanged. In the intestine the GIP cells were markedly reduced in number in the jejunum of the functional intestine of the JIB rats and the jejunum from the MSBR rats. The GIP cells in the jejunum of the bypass loop did not differ from the control jejunum. The results indicate that the high basal GIP levels seen in the JIB rats were the result of GIP secreted from the blind loop. This study also confirmed the decreased sensitivity of the beta-cells to GIP after JIB while indicating that MSBR has little if any effect on the response of the beta-cell to GIP. These data presented further evidence that the high basal GIP levels were causally related to the decreased insulin response in the JIB rats.

Animals↗
PubMed1982

Effect of jejunoileal bypass in the rat on the enteroinsular axis.

The effect of jejunoileal bypass (JIB) on the enteroinsular axis was studied in vivo and in vitro in the rat. Glucose, insulin and GIP responses to oral glucose were compared in JIB and control rats. The effect of glucose and GIP on insulin release from the isolated perfused pancreas of the same animals was investigated to determine if JIB altered the sensitivity of the beta cell. Immunocytochemical studies of gut and pancreas were also carried out. Glucose, insulin and GIP responses to a glucose load were blunted after JIB, although basal GIP levels were elevated in these animals. The insulin response of the perfused JIB pancreas to GIP was 70% reduced from controls although the insulin response to glucose appeared normal. The size and area of JIB islets were unchanged from controls as was the distribution of insulin, glucagon, somatostatin and pancreatic polypeptide. GIP immunoreactive cells were present in all regions of the intestine including the JIB blind loop. This study confirms the findings of others that a relationship exists between reduced GIP and insulin response to oral glucose after JIB, and indicates that a decrease in sensitivity of the beta cell to GIP occurs following JIB that is not rapidly reversible. GIP secreted from blind loop mucosa may contribute to the high basal GIP found in JIB rats and may be causally connected to the fall in beta cell sensitivity.

Animals↗
PubMedDate not supplied

Variability of thymidylate synthase activity in whole blood cultures treated with FUdR.

Induction of some fragile sites including fragile X [fra(X)] depends on the depletion of thymidine monophosphate (TMP) from the culture medium. This can be accomplished by use of inhibitors such as 5-fluorodeoxyuridine (FUdR) and by culturing cells in medium deficient in folate and TMP. FUdR inhibits the activity of thymidylate synthase (TS), thereby depleting cells of TMP. To determine the degree of FUdR inhibition of TS under routine cytogenetic culture conditions, we modified the tritiated dUMP TS method for use in short-term whole blood cultures stimulated with phytohemagglutinin. TS inhibition was highly variable across whole blood cultures from 30 individuals exposed to FUdR during the last 24 hours of a 4 day culture. If an additional dose of FUdR was added 12 hours before harvest, TS inhibition usually increased. These findings have a potential impact on the use of FUdR for the diagnosis of the fra(X) syndrome.

Blood Cells↗
PubMedDate not supplied

DNA linkage studies in the fragile X syndrome suggest genetic heterogeneity.

Previously, we showed genetic heterogeneity for linkage between the fra(X) locus and a factor IX DNA RFLP (Brown et al, 1985). When fra(X) families were predivided into two classes, one containing those with non-penetrant (NP) males and one with apparent full penetrance (P), evidence of significant heterogeneity was present. We have now extended this analysis by adding DNA linkage information on 2 additional probes, 52A and ST14, studied in 16 fra(X) kindreds. These data were combined with information on 16 published fra(X) families. There were 7 NP families and 25 P families. We confirmed our previous findings of a higher recombination fraction between factor IX and fra(X) in P families (0 = .32 with lod of .67) compared to as NP families (0 = .06 with lod of 6.11) which was significant at p less than .01. In comparing recombination fractions for the additional probes, more recombination between 52A and the other loci was consistently seen in P compared to NP families which suggested that there may be a higher rate of recombination proximal to the fra(X) locus in P kindreds. A strikingly higher recombination fraction between 52A and factor IX was present in comparing all fra(X) families (.18) to normal families (.02) which was significant at p less than .001. These results suggest genetic heterogeneity with respect to recombination is present both among fra(X) pedigrees and between fra(X) and normal pedigrees.

DNA↗
PubMedDate not supplied

Multipoint linkage of 9 anonymous probes to HPRT, factor 9, and fragile X.

We have analyzed the segregation of restriction fragment length polymorphisms (RFLPs) associated with 9 anonymous probes detecting loci DXS10, DXS15, DXS19, DXS37, DXS51, DXS52, DXS98, DXS99, and DXS100 and probes for HPRT and F9 in a set of 40 families segregating fragile X (fra(X]. Using two-point and multipoint analysis, we have established their relative genetic locations. The results indicate that DXS99 and DXS10, unlike previous reports, are not tightly linked to F9. A new locus was found to map within the F9 - fra(X) region. DXS98 showed 6% recombination with fra(X) and appeared to be the closest locus to fra(X). These results will be useful for mapping the relative position of newly defined X probes in this region and for future genetic studies of families with fra(X), hemophilia B, or Lesch-Nyhan mutations.

Chromosome Mapping↗
PubMedDate not supplied

Patterns of antibiotic susceptibility of gonococci isolated in Hong Kong, 1987-1990.

Among the 14,528 strains of Neisseria gonorrhoeae isolated from the Government Social Hygiene Sexually Transmitted Disease (STD) Clinics in Hong Kong between 1987 and 1990, there has been a trend toward a decrease in the percentage of penicillin resistant strains in both penicillinase-producing and nonpenicillinase producing N. gonorrhoeae (PPNG and non-PPNG) and an increase in moderate resistant strains, whereas the proportion of sensitive strains has remained stable, except for a small increase in 1990. Presently, PPNG still accounts for 31% of all isolates. In early 1991, 100 consecutive isolates were tested for minimum inhibitory concentrations (MIC) against 6 commonly used antibiotics. Although ofloxacin has been used as the first-line treatment for gonorrhea for the last 5 years, there is still no sign of in vitro resistance. Two isolates with high-level tetracycline resistance (MIC greater than 16 mg/l) were detected that have not been seen before. Sensitivity to spectinomycin, cefuroxime, and ceftriaxone has also been maintained, and these drugs can probably be recommended as alternative treatments in noncompliant cases. Analysis of location of contact shows an increasing proportion of cases of gonorrhea from overseas, particularly from parts of China. Comparison with the limited information published in the region shows that the population sampled can be very heterogeneous. With the continued flux of international travel, one should be extremely careful when trying to get an accurate assessment of epidemiologic data.

Anti-Bacterial Agents↗