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Biomedical subjects

S H Yap

Publications and source records attributed to S H Yap.

At least 91 records · Page 5Linked to original sources

Prospective comparison of gastric secretory function after gastrectomy with either Billroth II or Roux-en-Y anastomosis.

In order to delineate the role of enterogastric reflux in changes of postoperative gastric secretory functions, 22 patients with peptic ulcers, who were randomly assigned to partial gastrectomy without vagotomy with either Billroth II or Roux-en-Y anastomosis, were prospectively studied before and 6 months after surgery. Preoperatively, there were no significant differences in gastric secretory functions between the two groups of 11 patients. Postoperatively, median fasting bile acids in the stomach increased in the Billroth II patients from 0.35 to 16.10 mumol/hr (p less than 0.01), but significantly decreased in the Roux-en-Y patients from 0.30 to 0.10 mumol/hr (p less than 0.05), which indicated adequate prevention of enterogastric reflux after the Roux-en-Y procedure. Gastrectomy resulted in significant reductions of median values of basal acid output (4.6 vs 0.6 mmol/hr, p less than 0.01, and 4.2 vs 0.4 mmol/hr, p = 0.02), peak acid output (31.6 vs 4.2 mmol/hr, p less than 0.01, and 38.7 vs 4.5 mmol/hr, p less than 0.01), serum pepsinogen A (121 vs 86 micrograms/L, p less than 0.01, and 92 vs 45 micrograms/L, p less than 0.01), meal-stimulated serum gastrin secretion (1472 vs 199 pM.60 min, p less than 0.0001, and 1017 vs 199 pM.60 min, p less than 0.0001) in the patients with Billroth II and Roux-en-Y anastomosis, respectively. There were, however, no significant differences in gastric secretory parameters between the two groups when studied 6 months after surgery. Therefore it is concluded that after gastrectomy, enterogastric reflux does not affect the secretory function of the gastric remnant within the first 6 months after surgery.

Anastomosis, Roux-en-Y↗

Methanethiol and dimethylsulfide formation from 3-methylthiopropionate in human and rat hepatocytes.

This study was designed to investigate the metabolism of methanethiol, and the involvement of methanethiol and its metabolites in the transamination pathway of methionine. Gaseous methanethiol, methanethiol-mixed disulfides and dimethylsulfide were formed from 3-methylthiopropionate, a metabolite in the transamination pathway of methionine, during incubation with human and rat hepatocytes. An increase of the 3-methylthiopropionate concentration resulted in an increased formation of the products, up to a substrate concentration of 4.4 mM. Higher substrate levels resulted in a decreased methanethiol formation, probably due to poisoning of the system. However, in human hepatocytes the formation of dimethylsulfide increased up to a 3-methylthiopropionate concentration of 12.5 mM. The formation of methanethiol, dimethylsulfide and methanethiol-mixed disulfides from 3-methylthiopropionate in hepatocytes of both human and rat support the hypothesis that methanethiol can be formed from methionine via the transamination pathway.

Animals↗

Fibrinogen and albumin synthesis are regulated at the transcriptional level during the acute phase response.

During acute inflammation or after administration of monocytic products, an enhanced transcription of the fibrinogen polypeptide genes and a reduced transcription of the albumin gene were observed. The changes in the fibrinogen polypeptide transcriptional rate were found to precede the change in albumin gene transcription. These findings indicate that the altered synthesis of fibrinogen and albumin during inflammation are regulated at the transcriptional level and are most probably mediated by monocytic products (including interleukin-1).

Animals↗

The effect of interleukin-1, interleukin-6 and its interrelationship on the synthesis of serum amyloid A and C-reactive protein in primary cultures of adult human hepatocytes.

During the acute phase response, synthesis of C-reactive protein and serum amyloid A is increased. To investigate whether the enhanced synthesis of these proteins are due to stimulatory effect of inflammatory mediators such as interleukin-1 (IL-1) and interleukin-6 (IL-6) produced by macrophages and monocytes, primary cultures of adult human hepatocytes were exposed to recombinant (r)IL-1, rIL-6 or rIL-1 and monospecific anti rIL-6 antibodies in the presence of 1 microM dexamethasone. The findings indicate that rIL-1 and rIL-6 both stimulate the liver synthesis of C-reactive protein and serum amyloid A, however monospecific anti rIL-6 antibodies reduce the stimulatory effect of rIL-1 on the synthesis of these proteins. These findings suggest that IL-6 plays a key role in the stimulation of synthesis of serum amyloid A and C-reactive protein by the human liver cells.

Adolescent↗

Some metabolic characteristics of low-density lipoprotein subfractions, LDL-1 and LDL-2: in vitro and in vivo studies.

Two low-density lipoprotein subfractions, LDL-1 and LDL-2, with density ranges of respectively 1.023-1.034 and 1.036-1.041 g/ml, were isolated by aspiration after density gradient ultracentrifugation of human pooled serum. In vitro interactions of both LDL subfractions with the LDL receptor of human cultured fibroblasts, human hepatoma cell line Hep G2 and human hepatocytes were compared. No difference in association (binding and internalization) nor in degradation between LDL-1 and LDL-2 by these cells was found. However, kinetic studies in guinea pigs showed that LDL-2 disappeared faster from the circulation and accumulated to a greater extent in the liver, compared to LDL-1. Thus, we were unable to show a difference in the LDL receptor-mediated uptake of both LDL subfractions by various cells in vitro. The results obtained in vivo suggest that LDL-1 is more atherogenic than LDL-2, because its longer half-life renders the particle more susceptible to uptake by the scavenger LDL receptor on macrophages.

Animals↗

The prevalence of serological markers, hepatitis B virus DNA and elevated serum amino transferase values in institutionalized mentally handicapped males and females: an epidemiological study of HBV infection in residents with Down's syndrome or other forms of mental deficiency.

Conventional HBV serological markers, as well as serum alanine amino transferase and hepatitis B virus DNA (HBV DNA) were studied in a population of 667 institutionalized mentally handicapped males and females and in 676 staff members. The role of Down's syndrome (DS), sex and age-related factors with respect to the prevalence of these markers was analyzed. A young age at admission was found as one of the important factors in the development of the chronic HBsAg carrier state in females. The well-known higher prevalence of HBsAg carriership in DS patients appeared to be restricted to males. Markers indicative of viral replication, HBeAg and HBV DNA, were also more prevalent in male than in female DS residents, or OMR residents. These findings indicate that the phase of active viral replication is prolonged in male HBsAg carriers with DS. However, only 66.7 per cent of HBV DNA-positive and 26.2 per cent of HBsAg-positive residents had abnormal serum alanine aminotransferase (ALT) values. In addition, more than 50 per cent of residents with elevated serum alanine amino transferase values were negative for HBV serological markers. We conclude that male DS residents are the main source of HBV infection in institutions for the mentally handicapped and that determination of ALT values is not very useful in identifying those HBsAg carriers capable of transmission the infection.

Age Factors↗

Molecular aspects of age-related changes in albumin synthesis in female WAG/Rij rats.

The rate of albumin gene transcription and the level of albumin RNA sequences in liver nuclei of rats of various ages were determined to investigate the regulation of age-related changes in levels of cytoplasmic albumin mRNA in rat liver. No change was observed with age in both the rate of albumin gene transcription and the amount of nuclear albumin RNA sequences, which suggests that the increase in cytoplasmic albumin mRNA content in the rat liver with age is caused by a decreased turnover of this messenger. The length of poly(A)-tails of rat liver cytoplasmic RNA with age was also examined. Although no change with age was observed in the poly(A)-tail length sedimenting at the peak fraction, a shift towards shorter poly(A)-tails was found with age in the overall poly(A)-tail length distribution.

Aging↗

Albumin elimination in female WAG/Rij rats with age: a longitudinal study.

A longitudinal study was performed to examine total albumin elimination and urinary albumin excretion in the female WAG/Rij rat. Complete necropsies were performed following the spontaneous death of the animals. The survival characteristics of this group was similar to that of survival cohorts. An increase in total albumin elimination, urinary protein excretion and urinary albumin excretion was observed with age. A proportional increase in the contribution of albumin to the urinary protein excretion was also observed. However, the observed increase in urinary albumin excretion could not totally account for the increase in total albumin elimination. The predominant kidney lesion was chronic progressive nephrosis. The histological severity of the renal lesions were closely correlated with the increase in urinary albumin and total protein loss. It is concluded that the increase in total albumin elimination in rats in this study was due to age-related changes and not to cohort effects.

Aging↗

In vitro infection of primary cultures of cryopreserved adult human hepatocytes with hepatitis B virus.

Infection with HBeAg and HBV DNA positive serum in primary cultures of cryopreserved human hepatocytes in the presence of human whole blood in the medium was performed in 8 consecutive experiments. HBsAg and HBV DNA release into the medium was increased in the second week after infection. Via immunostaining, HBcAg was first observed in the nucleus of hepatocytes approximately 3 days after infection. A maximal percentage of HBcAg positive cells in 0.1% of cultured hepatocytes was detected on the 7th day. HBsAg was also first demonstrated on the 3rd day, and predominantly localized in the cytoplasm. About 5% of hepatocytes were HBsAg positive on the 12th day after infection. The percentage of positive cells did not appear to increase after this time. Using in situ cytohybridization and agarose gel electrophoresis and Southern blot analysis, HBV DNA was first detected on the 4th day. In addition, electron microscopic studies revealed the presence of 42 nm virus-like particles in the cytoplasm of infected cells in the second week after infection. This in vitro system provides a model for studying the mechanism of HBV infection, viral replication and maturation. However, further improvement of culture systems is needed, to increase the number of infected cells and for active HBV replication.

Cell Nucleus↗

Isolation and culture of Kupffer cells from human liver. Ultrastructure, endocytosis and prostaglandin synthesis.

Kupffer cells and other sinusoidal cells were isolated after perfusion and incubation with pronase and collagenase of pieces of liver tissue obtained from organ donors. The resulting cell preparations contained endothelial cells, Kupffer cells and fat-storing cells as well as considerable numbers of leucocytes. Attempts to purify the different sinusoidal cell types by density centrifugation and centrifugal elutriation were successful only for Kupffer cells. Kupffer cells, in contrast to endothelial cells and fat-storing cells, could be kept in maintenance culture for at least 5 days. Cultured Kupffer cells were active in the endocytosis of foreign substances, such as colloidal carbon, latex beads, horseradish peroxidase and bacterial endotoxin. The cultured Kupffer cells synthesized and secreted considerable amounts of prostaglandins PGE2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane B2. The production of prostaglandins was influenced by the presence of Escherichia coli endotoxin.

Cells, Cultured↗

Primary culture of cryopreserved adult human hepatocytes on homologous extracellular matrix and the influence of monocytic products on albumin synthesis.

Cultured human hepatocytes provide a useful method for studies of specific metabolic functions, such as plasma protein synthesis or drug metabolism in man and specific interaction of microorganisms with the human liver cell. In vitro studies using human hepatocytes are seriously hampered by the limited availability of viable tissue and the lack of suitable methods for preservation of hepatocytes. In addition, normal adult human hepatocytes, under classical culture conditions, do not proliferate in vitro. Recently, we have reported a method for long-term storage of human hepatocytes, using a cryopreservation technique. However, after thawing, the efficiency of cell seeding onto tissue culture plastic and, accordingly, the survival of hepatocytes in primary cultures were decreased as compared to freshly prepared and cultured hepatocytes. In the present study, we report the effects of extracellular matrix (ECM) obtained from normal liver of kidney donors on the attachment efficiency, survival, some metabolic functions and fine structure of human hepatocytes. It was found that the deleterious effect of deep-freeze storage on attachment efficiency and survival of hepatocytes could be significantly reduced by using tissue culture plastic precoated with human liver ECM. Hepatocytes survived for more than 4-6 weeks, without evidence of fibroblast overgrowth. Using this in vitro experimental system, we have also shown that these hepatocytes synthesize several liver-specific acute phase proteins, and monocytic products were able to decrease the hepatocytic synthesis of albumin while total protein synthesis remained unchanged. These results support our previous observations in cultured rodent hepatocytes, indicating the important role of monocytic products in the regulation of liver synthesis of albumin in inflammatory diseases in man.

Albumins↗

Etiologic factors of jaundice in severely ill patients. A retrospective study in patients admitted to an intensive care unit with severe trauma or with septic intra-abdominal complications following surgery and without evidence of bile duct obstruction.

In order to understand the pathophysiology of jaundice in severely ill patients, we have examined several possible promoting factors in a retrospective study of 86 patients with multiple organ failure admitted to an intensive care unit (ICU). Patients with bile duct obstruction were excluded from this study. Cholestatic jaundice had developed in 19 of 54 patients after trauma and in 20 of 32 patients after septic intra-abdominal complications. No differences were found between the icteric and non-icteric groups of patients with regard to median age, sex distribution, duration of stay in the ICU, number of operations, utilization of gaseous and/or intravenously administered anaesthetics and lipid, and administration of potential hepatotoxic drugs. Twenty-six of 39 icteric patients had a normal renal function. However, a significantly higher number of blood transfusions was found in the icteric as compared to the non-icteric patients. The higher number of blood transfusions and the incidence of initial shock in the icteric trauma patients were probably related to the higher injury severity score. Furthermore, sepsis was found significantly more frequently in the icteric trauma patients, while the number of organ failures when the presence of jaundice was not accounted for was the same in both groups. Nevertheless, the severity of jaundice correlated well with the increasing number of failing organs and the increasing mortality. From these findings we can therefore conclude that jaundice occurring in patients with multiple organ failure is usually not due to the administration of potential hepatotoxic drugs. However, the number of blood transfusions may be an important associated factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prostaglandins E2 and F2 alpha are not involved in the monocytic-product (interleukin-1)-induced stimulation of hepatic fibrinogen synthesis in rats.

1. Monocytic products, especially interleukin-1 (IL-1), play an important role in the acute-phase response. Prostaglandins have been shown to act as second messengers in several physiological alterations of the acute-phase response, such as fever, muscle wasting and immunoregulation. The present study was undertaken to determine the role of prostaglandins in the monocytic-product-induced stimulation of the hepatic synthesis of fibrinogen, a well-known acute-phase protein. 2. Prostaglandin (PG) E2, PGF2 alpha and 16,16-dimethyl-PGE2 did not stimulate fibrinogen synthesis and fibrinogen polypeptide mRNA content when administered intraperitoneally to rats or when added to monolayer cultures of rat hepatocytes. 3. Cyclo-oxygenase inhibitors did not abolish the stimulation of fibrinogen synthesis and its mRNA content induced by monocytic products in vivo or in vitro. 4. These findings indicate that the enhanced synthesis of fibrinogen induced by monocytic products (including IL-1) during the acute-phase response is not mediated by prostaglandins or other products of the cyclo-oxygenase pathway of arachidonic acid.

Animals↗

Hepatitis B virus infection in an institution for the mentally retarded.

A cross-sectional survey on the prevalence of hepatitis B serologic markers and hepatitis B virus DNA was performed in a population of 493 mentally handicapped males. Special interest was focused on age-related variables such as age at entry into the institution and on duration of residency. Furthermore, the differences with regard to the prevalence of hepatitis B markers found in Down's syndrome residents and other mentally retarded persons were analyzed. In a longitudinal study, the impact of the presence of hepatitis B virus DNA in serum was studied. Overall, 62.1 per cent of residents had serologic evidence of infection with hepatitis B virus, while 16.7 per cent of those residents with markers of infection were positive for hepatitis B surface antigen (HBsAg). Hepatitis B virus DNA was found in 24 per cent of HBsAg carriers (all positive for hepatitis B e antigen (HBeAg). In residents whose age at entry was less than 15 years, those with Down's syndrome were more often carriers of HBsAg than other mentally retarded residents. In addition, Down's syndrome residents more often had serum hepatitis B virus DNA compared with residents with other forms of mental retardation. A young age at entry was recognized as an important factor with regard to the prevalence of hepatitis B markers. From the longitudinal studies, it appeared that loss of hepatitis B virus DNA from serum indicated imminent loss of HBeAg and normalization of alanine aminotransferase values. Knowledge of the hepatitis B virus DNA status of HBsAg carriers in these institutions may therefore provide a valuable tool in attempts to reduce the transmission of this infection.

Adolescent↗

[The variable picture of gastric carcinoid].

Carcinoids are endocrine tumors which develop from enterochromaffin cells and will be found in more than 80% in the gastrointestinal tract. Only 2-3% of these carcinoids is located in the stomach. The rarity of their occurrence and the wide variety of radiographic features (intramural defects, multiple gastric polyps, large gastric ulcers and polypoid intraluminal lesions) make their recognition difficult. We report 3 cases of gastric carcinoid, one of them presented with pernicious anemia, which has been reported more frequently in literature. One patient showed the unusual combination of adenocarcinoma and a carcinoid with a stalk in the stomach.

Adenocarcinoma↗

Study of the molecular mechanism of decreased liver synthesis of albumin in inflammation.

Hypoalbuminemia in inflammatory disorders is not an infrequent finding. However, little is known about albumin synthesis in these patients. In the present study we have measured the albumin synthesis in four patients with inflammatory diseases using the [14C]carbonate technique. Because inflammation causes a decreased albumin synthesis and this decreased synthesis could not be related to a reduced amino acid supply, we have also examined the possible molecular mechanisms of reduced albumin synthesis during inflammation using in vivo and in vitro experiments in rats. In rats with turpentine-induced inflammation, serum albumin concentration and liver albumin mRNa level were markedly decreased. These changes could not be reproduced by administration of fibrinogen-, or fibrin-degradation products, or several hormones, such as corticosteroids, growth hormone, and adrenaline. However, monocytic products, especially interleukin 1, postulated to be important mediators of the inflammatory response, reduced albumin synthesis and liver albumin messenger RNA content but not total protein synthesis in rats in vivo and in primary cultures of rat hepatocytes. These findings suggest that monocytic products play an important role in reduced albumin synthesis during inflammation.

Adult↗