Biomedical subjects
Publications and source records attributed to L Chan.
An epidemic of serologically confirmed hepatitis A occurred between May and September 1983 in Singapore. The vehicle of transmission was traced to raw and partially cooked cockles, Anadara granosa, which had been imported from places with no sanitary control on the production. Strict controls on imported cockles are warranted.
Diabetes mellitus can affect every organ system, including large and small blood vessels, eyes, nerves, kidneys, and the gastrointestinal (GI) tract. We reviewed recent knowledge concerning the impact of diabetes on the gut. While the incidence of GI tract complications is usually considered relatively low, functional alterations have been demonstrated at every level in the gut and account for considerable morbidity in the diabetic population.
ApoA-I is the major human HDL apoprotein. By oligonucleotide hybridization, we have isolated 5 dscDNA clones to human hepatic apo A-I mRNA. One of these clones (pA1-3) was completely sequenced. It has 878 bp plus a poly A tail of 48 and includes all the coding and 3'-untranslated regions of the mRNA and part of the 5'-untranslated region. It predicts a peptide sequence of 267 amino acids (including the 24 amino acid prepropeptides) which is very similar to the sequence reported by Brewer et al., (1978) Biochem. Biophys. Res. Commun. 80:623-630. The predicted signal peptide sequence is highly homologous to the rat apoA-I signal peptide. There is no evidence for any internally repeated segments in apoA-I either at the amino acid or at the DNA level. Using pA1-3 as a probe, we have detected on Northern gels apo A-I mRNA sequences of approximately 1100 nucleotides in human hepatic and baboon hepatic and intestinal RNAs, but not in RNAs from baboon skeletal muscle, kidney or spleen. The demonstration of apo A-I mRNA sequences in specific organs is important to our concept of "reverse cholesterol transport".
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The effects of amiloride hydrochloride on thiazide-induced hypokalemia were evaluated. In metabolic balance studies, amiloride reversed thiazide-induced urinary potassium loss, restored plasma bicarbonate concentration and pH to pretreatment levels, and produced further increases in aldosterone secretion. Effects of long-term administration of hydrochlorothiazide and an amiloride-hydrochlorothiazide combination were compared in outpatients who had experienced thiazide-induced hypokalemia while receiving oral potassium supplements. After eight weeks, those given hydrochlorothiazide alone had an average serum potassium level of 3.01 +/- 0.08 mEq/L). Those given the amiloride-hydrochlorothiazide combination had an average serum potassium level of 3.75 +/- 0.008 mEq/L, not significantly different from the control value (3.82 +/- 0.08 mEq/L). Both groups had increased plasma aldosterone concentrations and plasma renin activity. The potassium-conserving effect of amiloride persisted with extended therapy.
More than 200 samples of esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) and levonorgestrel (13 beta-ethyl-17 alpha-ethynyl-17 beta-hydroxygon-4-en-3 -one) have been analysed by a combination of techniques, including high performance liquid chromatography (HPLC). Compounds having a purity below the required limit (99.5%) were purified, mainly by preparative HPLC, prior to formulation and biological evaluation as long-acting progestogens.
The biosynthesis of somatostatin has been studied at the ultrastructural level in pancreatic islets by using rabbit antiserum against synthetic somatostatin. To document that the antiserum specifically bound preprosomatostatin, we have tested the ability of the antiserum to precipitate the product synthesized in vitro. Poly(A) enriched RNA isolated from catfish islets was translated in both the wheat germ extract and nuclease-treated reticulocyte lysate systems. It was found that the in vitro translation product, preprosomatostatin, could be recognized by the antibody against synthetic somatostatin. The morphological study was then performed by immunoelectron microscopy by using the Fab-peroxidase conjugate technique. In dog pancreatic islets, somatostatin immunoreactive reaction product was seen only in the delta cells. In these cells, they were detected on bound ribosomes, in the cisternae of the rough endoplasmic reticulum (ER) and Golgi apparatus, in the Golgi associated vesicles, and in secretory vesicles. These findings suggest that somatostatin precursor molecules are synthesized on bound ribosomes and discharged into the cisternae of the rough ER. They are then transported to the Golgi apparatus and transferred to the secretory vesicles for secretion. The different staining intensities in the secretory vesicles would suggest that the processing of the precursor molecules of somatostatin probably takes place in the secretory vesicles.
A 40-year-old woman had a 1-year history of amenorrhea-galactorrhea. She was found to have an intrasellar tumor with suprasellar extension and a prolactin level of 98.1 ng/mL. Subtotal resection of the tumor resulted in a return of the prolactin level to normal within 4 days of the operation and of the prolactin response to thyrotropin releasing hormone, accompanied by the disappearance of the galactorrhea. Histologic examination revealed a typical craniopharyngioma. These observations indicate that one important mechanism of hyperprolactinemia in patients with craniopharyngioma is direct encroachment on the hypothalamus and/or pituitary stalk by the tumor and interruption of prolactin inhibiting factor.
The transient purpura in 3 young men with marked eosinophilia and hookworm infestation was found to be caused by a qualitative platelet defect which manifested as a failure of platelets to aggregate with collagen and an absence of the secondary phase aggregation with epinephrine. These aggregation abnormalities could not be normalized with normal plasma, nor did patient plasma inhibit normal platelets, implying that the dysfunction was not caused by an abnormality in the plasma but was an intrinsic platelet defect. Arachidonic acid induced enhanced aggregation and a mutual correction of the absent secondary epinephrine-induced aggregation was observed when patient and aspirin-treated platelets were mixed together, suggesting that the defect was unlikely to be related to the platelet prostaglandin synthesis pathway. We propose that the acquired platelet dysfunction was caused by impaired ADP release due possibly to a transient platelet storage pool abnormality.
Twenty-six Pseudomonas aeruginosa strains from patients with cystic fibrosis were typed by the Fisher immunotyping scheme. Only 6 strains were agglutinated by a single typing serum, whereas 15 strains were agglutinated with more than one serum and 5 were not agglutinated by any serum. Neither the polyagglutinable nor the nonagglutinable strains were typable by hemagglutination inhibition or immunodiffusion, suggesting that these polyagglutinable strains did not express multiple serotype antigens, but were instead being agglutinated by antibody to nonserotype determinants. Four typable isolates were resistant to pooled normal human serum, whereas the 12 polyagglutinable and nonagglutinable isolates studied were very sensitive to normal human serum. The outer membranes of 16 strains were isolated and characterized. The data suggested, in general, strong conservation of outer membrane protein patterns. Lipopolysaccharides (LPS) were purified by a new technique which allowed isolation of both rough and smooth LPS in high yields. Three of four typable, serum-resistant strains examined had amounts of smooth, O-antigen-containing LPS equivalent to our laboratory wild type, P. aeruginosa PAO1 strain H103. In contrast, 10 of 12 polyagglutinable or nonagglutinable, serum-sensitive strains had very little or no smooth, O-antigen-containing LPS, and the other two contained less smooth LPS than our wild-type strain H103. In agreement with this data, five independent, rough, LPS O-antigen-deficient mutants of strain H103 were nontypable and serum sensitive. We suggest that the LPS defects described here represent a significant new property of many P. aeruginosa strains associated with cystic fibrosis.
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ApoVLDL-II, the major very low density lipoprotein (VLDL) apoporotein, is also a major yolk protein in the chicken. The response of apoVLDL-II mRNA to estrogen treatment in 5-week-old cockerels was studied by hybridization to a nick-translated probe from cloned apoVLDL-II DNA. Following either primary or secondary stimulation (9 days after primary stimulation) of cockerels with 17 beta-estradiol (5 mg/kg), apoVLDL-II mRNA concentration increased from basal levels of 0.5 and 3.7 molecules/nuclear DNA equivalent respectively by 500- to 1000-fold within 3 h. The concentration of apoVLDL-II mRNA after 3 h during the secondary stimulation reached a level (1800 molecules/cell) 3.6-fold higher than that attained by primary stimulation (500 molecules/cell) at the same time point. Plasma 17 beta-estradiol concentrations following primary and secondary hormone treatment were similar during this time.
Pregnancy is associated with an increase in the extravascular fluid by about two litres. The regulation of fluid flux across capillary membrane is dependent on the STARLING's forces. Thus increased fluid shift into the extravascular space may occur during pregnancy when the intra-capillary hydrostatic pressure exceeds the opposing influence of plasma colloid oncotic pressure (COP). In order to evaluate these forces more fully, COP, hematocrit (HCT), serum total solids (STS), mean blood pressure (MBP) and MBP-COP gradient (M-C) were measured cross-sectionally in 184 women with normal uncomplicated pregnancy. COP fell gradually during the first and second trimesters, lowest at 30-34 weeks, thereafter it rose. The relationship of COP and gestational age was best described by the quadratic equation. The patterns of changes of HCT and STS with respect to gestational age were similar to COP. MBP and M-C were linearly correlated to gestational age. The increment in M-C with advancing gestational age would promote fluid flux from intra to extravascular space in normal pregnancy.
30 unselected patients with various entities of the myeloproliferative syndrome were entered into a prospective study to evaluate the relationship between platelet aggregation abnormalities and hemostatic complications and the role of aggregation study in myeloproliferative disorders. 21 patients showed impaired collagen-induced aggregation and absent second phase epinephrine-induced response. 6 of these patients had bleeding manifestations. 4 patients hyperaggregated with ADP, collagen, epinephrine and arachidonic acid. Of these, 3 had thrombotic complications as their initial presentation. In the 6-40 months follow-up no new cases of bleeding or thromboembolic phenomena were encountered among the remaining patients. In 3 patients aggregation abnormalities heralded the specific myeloproliferative disorder by months or years. We conclude from this study that routine platelet aggregation study in classical myeloproliferative disorders is unwarranted as it is costly and does not improve the diagnostic accuracy nor yield any predictive information concerning the tendency to bleed. It is useful as an accessory investigative tool in the atypical or early myeloproliferative patient whose clinical features, blood and marrow findings although suggestive are not diagnostic of a specific myeloproliferative entity.
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The forearms of six patients with Duchenne dystrophy were examined by the painless and non-invasive technique of high-resolution nuclear magnetic resonance spectroscopy. The phosphorus spectrum was abnormal in that the ratios of phosphocreatine to adenosine triphosphate and to inorganic phosphate were reduced. Absolute quantification under the conditions of this experiment was not possible but it was probable that in dystrophy the concentration of phosphocreatine in muscle was appreciably reduced. A signal in the phosphodiester region of the spectrum was recorded consistently in patients with dystrophy but not in controls. The intracellular pH of the muscle in the dystrophic patients was abnormally alkaline. The clinical application of nuclear magnetic resonance spectroscopy remains to be proved, but it appears to be a promising non-invasive technique for investigating biochemical abnormalities of muscle disease.
Azathioprine and steroids (prednisone or prednisolone) form the basis of conventional immunosuppression after renal transplantation. Most of the morbidity in the early months after transplantation. Most of the attributed to steroids, which are normally give in high doses. The only justification for giving high doses is a historical one. For this reason a randomised controlled trial was carried out to compare the efficacy of high dose (39 patients) and low dose (33 patients) oral prednisolone, both in combination with azathioprine, in patients given cadaveric renal allografts. Patients were followed up for at least two years after the transplantation. Patient and graft survival were identical in the two groups and the morbidity associated with steroids was impressively lower in patients receiving a low steroid dose. Although the optimal dose of steroids is still unknown, there seems little justification for continued use of high doses of oral steroids with azathioprine after cadaveric renal transplantation.
We have studied the sites of synthesis, assembly, and secretion of apoVLDL-II, a major apoprotein in very low density lipoproteins (VLDL), in the cockerel liver by immunoelectron microscopy. In the liver of the estrogen-treated cockerel, apoVLDL-II reaction products were localized in the cisternae of the nuclear envelope and the rough endoplasmic reticulum (RER). Such products were not observed in the smooth endoplasmic reticulum (SER). ApoVLDL-II reaction products were also located on the surface of lipid particles in the Golgi apparatus and secretory vesicles. Such lipid particles were not detected in the RER or SER. Some secretory vesicles containing the reaction products were seen during the process of fusion with the plasma membrane. Such fusion took place against the plasma membrane lining the space of Disse as well as the intercellular spaces. Reaction products also occurred in the sinusoids. These observations are compatible with the following sequence of events in the synthesis, assembly and secretion of apoproteins in VLDL in the cockerel liver: ApoVLDL-II is synthesized on bound ribosomes attached to the nuclear envelope and RER, and is discharged into their cisternae. The protein is probably transported to the Golgi apparatus where the assembly of this protein and its lipid components probably takes place. Secretory vesicles derived from the Golgi apparatus carry the VLDL particles to the plasma membrane where secretion of these particles takes place by exocytosis, and the VLDL are discharged into the sinusoid via both the space of Disse and intercellular spaces.