Search PubMed⌕ Search

Biomedical subjects

L Chang

Publications and source records attributed to L Chang.

At least 379 records · Page 21Linked to original sources
PubMed1978

Effects of Aureomycin on bile acids in rats.

Primary BA's secreted into the duodenum are extensively altered by bacteria in the large intestine. Such changes are not found in GF animals. As a result, GF rats reabsorb BA much more efficiently than do CV controls, and BA and cholesterol pools are higher in GF than CV rats. This indicates the importance of the intestinal flora in the homeostasis of cholesterol metabolism. Antibiotics can affect the extent to which BA's are altered by bacteria. In some cases, the antibiotic treatment also affects cholesterol levels in serum or liver. We have found that treatment of CV rats for only 5 days with low levels of Aureomycin (0.85 micron) led to a predominance of omega-MC over HDC in the feces at 10 days after withdrawal of the antibiotic. This reduced the usual HDC/omega-MC ratio from approximately 2.0 to 0.9 or less. These rats were also found to have liver cholesterol levels modestly elevated over those of controls. In other experiments the decrease in hyodeoxycholate/omega-muricholate ratio was found to persist for at least 90 days after discontinuation of treatment. Later experiments carried out with Aureomycin and with penicillin revealed the possible existence of a resistance factor to Aureomycin. A significant lowering of the hyodeoxycholate/omega-muricholate ratio was now found only with antibiotic concentrations 10 to 100 times greater than those used previously. Possible implications of the persistence of antibiotic effects, as measured by changes in fecal BA's, include effects on vitamin metabolism, colon cancer, and cholesterol metabolism.

Animals↗
PubMed1977

Effect of autoclaving of a lactose-containing diet on cholesterol and bile acid metabolism of conventional and germ-free rats.

Feeding of lactose in amounts comparable to the adult human intake in developed countries (6% of diet, and in later studies 10%) had no major effect on cholesterol and bile acid metabolism of germ-free and conventional rats. However, when lactose-containing casein-starch diets were sterilized by autoclaving, changes in intestinal and/or fecal bile acids were found. Both germ-free and conventional rats demonstrated some increase in intestinal beta-muricholic acid concentrations ascribable to the mere presence of lactose in the diet. Autoclaving of the diet produced additional changes, especially in the fecal bile acid pattern of conventional rats. Here the ratio between the beta-muricholic-derived secondary bile acids hyodeoxycholic and omega-muricholic acids changed from the usual 5:3 to approximately 1:10, with omega-muricholic acid becoming the major fecal bile acid. These changes point to a notable effect of lactose-derived products, formed during steam-sterilization, on the microbial modification of intestinal bile acids in the lower gut. Similar changes have been observed after oral administration of aureomycin and other, unrelated antibiotics that inhibit growth of gram positive organisms.

Animals↗
PubMed1976

Effect of dietary lactose at levels comparable to human consumption on cholesterol and bile acid metabolism of conventional and germfree rats.

In recent years, the use of milk products and the concomitant intake of lactose have been tentatively linked to the etiology of cardiovascular disease. An effect of lactose on the microbial modification of acid and neutral sterols has been suggested. In the present study lactose intake, ranging up to 30% of total diet increased beta-muricholic (beta-MC) but not cholic acid concentrations in conventional (CV) rat small intestine to the extent that at the 20% and 30% intake level, the intestinal cholic: beta-MC ratio approached that in germ-free (GF) rats. Total intestinal bile acid (BA) content increased by approximately 1/3, but remained at less than half the value found in GF rats. At lactose intake levels within a range corresponding to the consumption of dairy products often recommended for adult man (5% to 10%) only moderate changes in intestinal, and little change in fecal BA were found during and after the 3 months experimental period. Intestinal beta-MC was increased in the presence and in the absence of an intestinal microflora. Experiments with GF rats fed 10% lactose or 10% maltose indicated that this increase is evoked similarly by both carbohydrates. The slight increase in serum cholesterol levels seen with disaccharide feeding, which became evident only in the GF rats, was again not specific for lactose. No influence was found of lactose feeding on liver cholesterol values. Comparison of CV rats fed nonsterile and radiation-sterilized lactose-containing diets suggested that this mode of sterilization has only a minor influence on the resulting data. When GF experiments are to be incorporated, sterilazation of diet by irradiation with 3.5 to 4.0 X 10(6) Rad is preferable to autoclaving. The present data indicate that no major effect specifically related to a normal dietary intake of lactose on cholesterol and BA metabolism of the adult rat could be demonstrated for the duration of these experiments.

Animals↗
PubMed1976

Analysis of bile acids in conventional and germfree rats.

The well-known bile acid analysis technique used by us and others (Grundy, Ahrens, and Miettinen. 1965. J. Lipid Res. 6:397-410) does not allow for the detection of hyodeoxycholic acid, a product of quantitative importance in rodent feces. Using updated methodology, it was established that hyodeoxycholic acid and omega-muricholic acid, both apparent conversion products of beta-muricholic acid, occur in apppreciable amounts in intestinal contents and feces of conventional Wistar type Lobund rats. In conventional rats, these bile acids comprise about 50% of fecal bile acids; they are not found in intestinal contents or feces of germfree rats. Others have demonstrated that hyodeoxycholic acid if formed by combined action of gut flora and liver. A new method for the separation of conjugated and free bile acids in biological samples was developed. Results with this method confirmed the total conjugation of bile acids in the germfree rat, and the almost total deconjugation that takes place in the cecum of the conventional rat.

Animals↗
PubMed1976

Rauwolfia derivatives and breast cancer.

During the course of a collaborative study initiated in investigate the relationship of breast cancer and the use of hormones, it was possible to study the possible relationship of rauwolfia derivatives, mainly reserpine, to breast cancer. Interviews were administered to breast cancer patients admitted to five hospitals in the Baltimore metropolitan area. The study of reserpine use was conducted for a period of approximately one and a half years and information on reserpine use was obtained on 164 breast cancer cases. Each case was matched with a control with respect to age, color, hospital of admission, and admission date. An additional set of controls was drawn from women residing in the same neighborhood as the cases. Neither reserpine, methyldopa, nor thiazides were found to be significantly associated with breast cancer. The exclusion from the analysis of hospital controls with a diagnosis of hypertensive disease and their matched cases did not significantly alter the results. Those cases who used reserpine, used more for longer periods of time than did the controls, however this was judged inconclusive due to a considerable amount of missing data. After comparison of these results with previously reported studies, it did not appear that reserpine was strongly associated with breast cancer. However, because of methodological problems and differences between the studies, a possible small overall relationship could not be definitely excluded.

Adolescent↗
PubMed1975

Primary structure of a deleted human lambda type immunoglobulin light chain containing carbohydrate: protein Sm lambda.

An internal molecular deletion occurring in a human lambda type immunoglobulin light (L)-chain (Sm lambda) has been defined by sequence analysis. The Sm protein was isolated from the urine of a patient with a plasma cell dyscrasia involving the synthesis of an IgG molecule with both deleted gamma and lambda subunits. The Sm lambda polypeptide chain has an approximate molecular weight of 15,000 and contains 135 amino-acid residues. The constant (C) region is fully intact, comprising 105 residues, whereas the variable region (V) has only 30 residues. The V-region segment represents residues 1 through 30 of normal lambda chains and possesses considerable homology (87%) to lambda chains of subgroup II. Since lambdaII proteins normally contain 216 amino-acid residues, the defect represents an intramolecular deletion of 81 residues, which is entirely confined to the carboxyterminal three-quarters segment of the V-region, with a resumption of normal synthesis at a glutaminyl residue at position 110, the initiation point of the C-region. Carbohydrate is attached to an Asx residue at position 25, in the first hypervariable region, associated with the sequence triplet Asx-Ser-Ser, which is postulated to be a common recognition site for glycosylation of immunoglobulins. The carbohydrate moiety is a complex oligosaccharide with a branched chain structure containing sialic acid, fucose, mannose, N-acetylglucosamine, and galactose. These structural studies and other findings suggest that restricted areas in the DNA of immunoglobulin genes, such as the hinge regions of heavy (H) and light (L) chains and the hypervariable regions, are particularly susceptible to breakage and reunion. We postulate that the genetic defect of protein Sm could have originated from a somatic mutational event in the plasmacyte precursor during or after the integration of the V and C genes. These studies provide additional support for the hypothesis and two distinct structural genes encode a single immunoglobulin polypeptide chain.

Amino Acid Sequence↗
PubMed1972

Thyrotropin increases prostaglandin levels in isolated thyroid cells.

We have shown that two unrelated prostaglandin antagonists block both thyrotropin (TSH) and prostaglandins E (PGE(1), PGE(2)) stimulation of thyroidal adenyl cyclase activation and cyclic 3',5'-adenosine monophosphate (cAMP) formation, suggesting that prostaglandins play an important role in regulating thyroid function. To further explore this postulate, we measured prostaglandin content by radioimmunoassay in homogeneous bovine thyroid cell preparations in the presence and absence of TSH. Antibodies to albumin-conjugated PGE(1) and PGF(2alpha) showed specificity for prostaglandins E and F, respectively, but reacted, albeit far less effectively, with heterologous prostaglandins. A double antibody system was used to separate free from antibody-bound PGE(1)-(3)H and PGF(2alpha)-(3)H. Thyroid cells were extracted with ethanol/ethyl acetate and the various prostaglandins separated on silicic acid columns. Recoveries of added PGE(1)-(3)H and PGF(2alpha)-(3)H through the extraction and separation procedures ranged from 50-80%. The sensitivity of the method was 10-50 pg. Basal thyroid cell content of PGE(1) and PGF(2alpha) "equivalents" varied between cell preparations (range = 2-6 ng/0.2 ml cell suspension) but, in each instance, remained constant during 5-30-min incubations at 37 degrees C. TSH, 10-100 mU/ml, increased the levels of cell PGE(1) and PGF(2alpha) "equivalents" 30-80% above basal during 5-15-min incubations. The stimulatory effect was specific for TSH, no increase in PGE(1) or PGF(2alpha) "equivalent" levels being seen with luteinizing hormone (LH), human growth hormone (HGH), adrenocorticotropic hormone (ACTH), or glucagon. These data support the thesis that prostaglandins may mediate TSH effects on thyroid.

Adenylyl Cyclases↗
PubMedDate not supplied

High density lipoprotein subpopulations in chronic liver disease.

Severe liver disease may be associated with a reduction in plasma concentration of high density lipoprotein and an impairment of plasma cholesterol esterification. These changes were confirmed in two patients with severe acute on chronic alcoholic liver disease. In five additional patients with biopsy-proven clinically compensated cirrhosis, there was minimal reduction in concentration of plasma cholesteryl esters; there was, however a reduction of the plasma high density lipoprotein concentration to only 48 to 66% of normal. The particle size distribution of high density lipoprotein in these five patients was determined by gradient gel electrophoresis. The high density lipoprotein2 subfraction was preserved. The high density lipoprotein3 subfraction, however, was markedly changed with a reduction in the normal particles of radius 4.3 m and an accentuation of smaller particles of radius 3.9 m; in two patients, these smaller particles were the major high density lipoprotein subpopulation. Further investigations of this finding of a distinctive distribution of high density lipoprotein subpopulations in patient with chronic liver disease may provide new insights into high density lipoprotein metabolism.

Adult↗
PubMedDate not supplied

Brain N-acetyl aspartate concentrations measured by H MRS are reduced in adult male rats subjected to perinatal stress: preliminary observations and hypothetical implications for neurodevelopmental disorders.

The present study was undertaken to determine if the concentration of brain N-acetyl-aspartate (NAA), a putative neuronal marker, is reduced in adult rats subjected to stress during the perinatal period. As the prenatal stressor, pregnant rats were subjected to restraint stress for one hour twice daily from days 14-21 of gestation; stressed offspring were reared by normal dams and studied as adults. As the postnatal stressor, normal pups were reared by prenatally 'stressed' dams and studied as adults. As compared to non-stressed controls (n=6), NAA concentrations were significantly reduced 21 and 25% in left frontal cortex from the prenatal (n=4) and postnatal (n=6) stress groups. respectively. The data suggest that in perinatally stressed adult offspring permanent neuronal damage or loss has occurred. While no direct causal associations between perinatal stress and the developmental of particular disorders can be inferred from these limited data, the effects of perinatal stress on subsequent brain neuropathology are reviewed. particularly in relation to NAA. For hypothesis-generating purposes, the possible relevance of stress and NAA to the neurodevelopmental hypothesis of schizophrenia is discussed in greater detail.

Age Factors↗
PubMedDate not supplied

The role of the immune system in conjunctival wound healing after glaucoma surgery.

The immune system has a fundamental role in the development and regulation of ocular healing, which plays an important role in the pathogenesis of most blinding diseases. This review discusses the mechanisms of normal wound healing, describing the animal and fetal wound healing models used to provide further insight into normal wound repair. In particular, conjunctival wound repair after glaucoma filtration surgery will be used to illustrate the contributions that the different components of the immune system make to the healing process. The potential role of macrophages, the possible regulatory effect of lymphocytes, and the important role of growth factors and cytokines in the wound healing reaction are discussed. The significance of the immune system in the pathogenesis of aggressive conjunctival scarring is addressed, particularly assessing the predisposing factors, including drugs, age, and ethnicity. The rationale behind the pharmacological agents currently used to modulate the wound healing response and the effects these drugs have on the function of the immune system are described. Finally, potential new therapeutic approaches to regulating the wound healing response are reported.

Animals↗
PubMedDate not supplied

Effects of cholecystokinin on gastric injury and gastric mucosal blood flow.

Cholecystokinin (CCK) is a vasodilator and prevents gastric injury from ethanol. Its effects against other irritants are unknown. This study was conducted to (1) assess whether CCK or oleate, a CCK secretagogue, could prevent gastric injury from other damaging agents and (2) examine the role of blood flow in CCK-induced gastroprotection. Conscious rats were pretreated for 10 minutes with intravenous saline solution or CCK (5 nmol/kg) or were given 1 ml of orogastric water or oleate (100 mmol/L) 30 minutes before a 1 ml orogastric bolus of acidified ethanol (150 mmol/L hydrochloric acid/50% ethanol), 0.75N hydrochloric acid, or 0.2N sodium hydroxide. Rats were killed 5 minutes after receiving an irritant and the total area (mm2) of macroscopic injury was quantified. The duration of CCK-induced gastroprotection against acidified ethanol was examined at 5, 10, 30, and 60 minutes after its administration. Other rats had gastric mucosal blood flow determined (fluorescent microspheres) at identical time points. CCK and oleate decreased gastric injury from all three luminal irritants. CCK-induced gastroprotection was present for 30 minutes but only enhanced gastric mucosal blood flow at 5 and 10 minutes. These data suggest that endogenous CCK may play a role in gastric mucosal defense and that blood flow alone does not fully explain CCK gastroprotection.

Animals↗