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Biomedical subjects

T M Lin

Publications and source records attributed to T M Lin.

At least 109 records · Page 6Linked to original sources

Bovine pancreatic peptide: action on gastric and pancreatic secretion in dogs.

Bovine pancreatic peptide (BPP) is a straight chain peptide containing 36 amino acid residues that has recently been isolated from pancreatic tissue. At a dose of 40 mug/kg-h intravenously, it stimulated gastric acid secretion when given alone but inhibited the submaximal secretion induced by the C-terminal pentapeptide of gastrin. Basal pancreatic secretion of dogs was inhibited by BPP (1-10 mug/kg-h) inhibited pancreatic protein secretion but often showed a biphasic action on water-bicarbonate response, an initial augmentation followed by reduction. BPP (2-5 mug/kg-h) inhibited pancreatic water-bicarbonate and protein secretions induced by an infusion of secretin plus cholecystokinin. Des-tyrosyl-NH2 BPP lacking the C-terminal tyrosyl amide, failed to inhibit gastric acid induced by C-terminal pentapeptide of gastrin or pancreatic secretion induced by secretin. BPP had no hyper- or hypoglycemic, hyperkalemic, or diuretic actions in the dog.

Animals↗

Action of glucagon and aspirin on ionic flux, mucosal blood flow and bleeding in the fundic pouch of dogs.

Into vagally denervated (Heidenhain) pouches of 4 dogs 25 ml of 0.1 M HCl was instilled and removed at 30 min intervals for 6 hours. During the 4th, 5th, and 6th 30 min periods the acid instillate contained 5 mg/ml of aspirin. Aspirin significantly increased gastric-mucosal clearance of aminopyrine (mucosal blood flow), outputs of Na+, Ca++, Mg++, hemoglobin, and plasma transferrin-Cr51 into the pouch contents, and disappearance of H+ from lumen to mucosa. Glucagon, 50 mug/kg subcutaneously was given during irrigation with aspirin and again 1 hour later. Glucagon did not significantly affect loss of acid from lumen to mucosa or the increase in Na+, K+, Ca++, and Mg++ effluxes caused by aspirin. Glucagon significantly decreased mucosal blood flow and the hemorrhage and loss of plasma protein into the instillate induced by aspirin.

Aminopyrine↗

Dispensability of both the amide of phenylalanine and the carboxyl group of aspartic acid for the stimulation of gastric acid secretion by gastrin peptides in dogs.

Two derivatives of the C-terminal tripeptide of gastrin devoid of -NH2 from the phenylalanyl residue and of -COOH from the aspartic acid, MBOC-Met.Asn.Phe-OH (I) and MBOC-Met.Asp-OBenz.Phe-OMe (II), stimulated gastric acid secretion in the dog when infused intravenously at doses of 100 to 400 mug/kg-hr. Maximal responses induced by I and II were about 30-40% of that induced by the C-terminal tetrapeptide of gastrin. At a dose of 600 mug/kg-hr, I had an inhibitory action while II initially augmented and then inhibited acid production. Neither the C-terminal amide nor the carboxyl group of the aspartyl residue is essential for the gastric stimulatory activity of gastrin peptides.

Animals↗

Placental localization of human pregnancy--associated plasma proteins.

Frozen sections of human placenta were examined for the presence of four human pregnancy proteins, pregnancy-associated plasma proteins A and C (PAPP-A and PAPP-C), human chorionic somatomammotropin (hCS), and pregnancy zone protein (PZP), by the indirect immunofluorescence technique. Monospecific rabbit antiserums to PAPP-A, PAPP-C and hCS all stained the trophoblast cytoplasm equivalently in a continuous layer, usggesting that the same trophoblast cells synthesize all three pregnancy proteins. In contrast, PZP was localized in blood vessel walls, parenchymal structures within the villous, as well as in the trophoblast cytoplasm. Its distribution in the latter was relatively inhomogeneous, tending to be more intense on the basement membrane side.

Blood Proteins↗

Relation of obstetric parameters to the concentrations of four pregnancy-associated plasma proteins at term in normal gestation.

The relations between normal obstetric parameters and the maternal levels of four pregnancy-associated plasma proteins (PAPP) were studied, with the use of plasma samples taken from 187 normal pregnant women within seven days before delivery. PAPP-A levels were correlated with placental and newborn weights. The levels of this pregnancy protein was higher in primigravid women and in groups with higher diastolic blood pressure than in other groups. Women with extremely high PAPP-A concentrations were likely to have extremely large placental weight was not necessarily associated with a high PAPP-A level. PAPP-C was not correlated with placental or newborn weight. The relationship between PAPP-C and maternal age, as well as maternal weight, was significant by one but not in the other three statistical analyses employed. The pregnancy zone protein was found to be correlated with parity. In primigravid women, this protein additionally showed an inverse correlation with the placental weight. Human chorionic somatomammotropin was significantly related to placental weight and inversely related to maternal weight. Its relationship with newborn weight was best seen in primigravid subjects. Other parameters (systolic blood pressure, one- and five-minute Apgar scores, weeks of gestation, days before delivery, newborn sex, and newborn bilirubin level) were not related to any of these pregnancy proteins.

Adolescent↗

Human pregnancy-associated plasma proteins during the postpartum period.

The plasma levels of four pregnancy-associated plasma proteins (PAPP's) and pregnancy zone protein (PZP) were studied in women after delivery of a single viable infant by gel immunodiffussion methods. Data from 89 random samples and 85 serial specimens from five women revealed that both PAPP-B and HPL (PAPP-D) disappeared within a day after delivery. PAPP-A showed a rapid drop in the first 2 or 3 days post partum and became nondetectable in 4 to 6 weeks, with a half-life of 3 to 4 days. PAPP-C had a sharp decrease by the second postpartum day and was not detected 3 to 4 weeks later, with a half-life of 1 to 2 days. None of the PAPP's was detected again during the rest of the 14 postpartum weeks studied. In contrast, the PZP showed a much slower decrease or even a temporary increase during the first 2 weeks post partum; it remained readily detectable over the entire 14 weeks studied.

Blood Proteins↗

Quantitative analysis of pregnancy-associated plasma proteins in human placenta.

By immunochemical methods and simultaneous measurements of several normal plasma proteins, human placenta was shown to contain elevated quantities of four pregnancy-associated plasma proteins (PAPP's). In the order of increasing amounts, PAPP-A, PAPP-C, PAPP-B, and human chorionic somatomammotropin (PAPP-D) all were present in placenta extracts in quantities greater than could be expected on the basis of their content in maternal blood. In sharp contrast, the placental content of pregnancy zone protein could be entirely accounted for by the maternal plasma present in the placenta. All of the PAPP's appeared to be readily extractible from placental tissue with buffered saline, the large bulk of them being solubilized in the first extraction procedure. However, absorption studies indicated that appreciable quantities of the PAPP's were still present in the insoluble placental residue after 12 sequential extractions with saline. The chorioamniotic membranes were not significantly enriched in any of the PAPP's. Immunochemical analysis of unwashed placental tissue extracts for the PAPP's IgA, and IgM (maternal blood derived), as well as albumin and transferrin (maternal and fetal blood derived), permitted calculations to be made of the amount of blood and PAPP's in placenta. On the basis of these data, it was roughly estimated that a 400-g placenta (wet weight) would occupy 312 ml in volume, and would contain 144 ml of blood. Of this blood, 36 ml would be derived from the mother.

Antibodies↗

Stimulation of gastric acid secretion in the dog by the C-terminal penta-, tetra-, and tripeptides of gastrin and their O-methyl esters.

Acid secretion from the vagally innervated gastric fistula of conscious dogs was stimulated in a dose-related manner by the C-terminal penta-, tetra-, and tripetide amides of gastrin, the o-methyl esters of the tetra- and tripeptides, and the sulfone derivative of the tetrapeptide amide. The potency and efficacy of Peptavalon and the C-terminal penta- and tetrapeptide amides were about the same on a weight or molar basis. On a molar basis, the pentapeptide amide was about 4300 times as potent as the tripeptide amide. The o-methyl ester and the sulfone derivative of the tetrapeptide were about equipotent; they were, respectively, one-twenty-fifth and one-thirtieth as potent as the tetrapeptide amide. The dipetide amides did not stimulate acid secretion in a dose range of 50 to 1500 mug per kg-hr. The results indicate that (1) the C-terminal tetrapeptide amide cannot be the minimal effective "stump" for biological activity in the gastrin molecule, (2) the C-terminal amide is important but not essential for gastric stimulating power, and (3) oxidation of the sulfur atom of the methionyl residue in the tetrapeptide does not result in total loss of activity.

Amides↗

Pregnancy zone protein analogue in pregnant and non-pregnant primates, and its decrease during pregnancy in some monkey species.

Rabbit antiserum to human pregnancy zone protein (PZP) cross-reacted with analogous proteins in several species of primates. The chimpanzee PZP showed reactions of identity with human PZP, while the PZP analogue in the orangutan, in four species of old world monkeys (pig-tailed, rhesus, cynomolgus and stump-tailed) and in a species of new world monkey (squirrel) showed equivalent reactions of partial identity with human PZP. In the chimpanzee and orangutan, the PZP analogue was present in low concentrations in non-pregnant animals, but as in the human, it increased quite appreciably during gestation. In the chimpanzee, this increase in pregnancy was about four-fold greater than in the human. In sharp contrast, in the old and new world monkeys, the PZP analogue was present in much higher concentrations in non-pregnant animals than it is in humans. In addition, during pregnancy the PZP analogue in these monkey species actually decreased during pregnancy. In the few cases studied, normal levels were regained about 1 month after delivery. A normal plasma protein, alpha2-macroglobin, was also studied in these primate species, because this protein shares some characteristics with PZP. Analogous alpha2-macroglobulin serum proteins were found in all the primates tested, but the observed gel diffusion identity patterns suggested that this protein was phylogenetically older than PZP. alpha2-macroglobulin increased slightly during human pregnancy, but in all the other primates studied, the alpha-macroglobulin analogue was either unchanged or slightly decreased during gestation.

Animals↗

Immunological comparison of various human pregnancy-associated plasma proteins.

Direct immunodiffusion comparison with specific antisera demonstrated that all of the four pregnancy-associated plasma proteins (PAPPs) described in our laboratory are distinct from the pregnancy zone protein (von Schoultz); alpha2-pregnoglobulin (Berne); pregnancy-associated alpha2-glycoprotein (SP3) (Bohn); new serum alpha2-macroglobulin (Stimson); PAG (Horne); pregnancy-associated alpha2-globulin (Kasukawa); Pal (McLaren), and Xh protein (Dunston). All the latter proved to be immunologically idnetical to each other, and apparently represent the same protein described under different names. It was confirmed that none of the PAPPs is immunochemically related to placental alkaline phosphatase. PAPP-A, PAPP-C, and the pregnancy zone protein, but not HPL (PAPP-D), showed a decreased anodic mobility when treated with neuraminidase; their reactivities with antibody were essentially unaffected by the ezyme, however. Certain detergents had no effect on the immunological reactivities of the PAPPs and the pregnancy zone protein in whole plasma, while butanol and desoxycholate partially, and urea, SDS and cetylpyridinium largely inactivated them.

Alkaline Phosphatase↗

Pentagastrin increases phenylalanine and decreases histidine incorporation to proteins of rat stomach.

Female rats were treated with L-phenylalanine-14C or L-histidine-14C, 20 mug/kg i.p. one hour before receiving pentagastrin 250 mug/kg s.c. Sixty minutes after injection of pentagastrin the incorporation of L-phenylalanine-14C into the proteins of the squamous and fundic portions of the stomach was significantly increased respectively by 18 and 17.5%. On the contrary, the uptake of Lhistidine-14C into the proteins of the squamous (-24%), fundic (-18% and duodenal (-16%) regions was significantly decreased. Incorporation of histidine and phenylalanine into the proteins of the pylorus was not significantly affected by pentagastrin.

Animals↗

Action of the anti-inflammatory agents, acetylsalicylic acid, indomethacin and fenoprofen on the gastric mucosa of dogs.

Into the Heidenhain pouches of 3 dogs 30 ml of 0.1N HCl was instilled and removed at 30-minute intervals for 6 hours. During the 3rd and 4th periods the acid instillate contained 4.5 mg/ml or 12.4 mM of ASA, indomethacin or fenoprofen. All 3 agents affected the functional integrity of the mucosal barrier, but the characteristics of their actions were different. The H+ concentration was decreased by ASA and fenoprofen and increased by indomethacin when the instillate contained drug. All 3 drugs increased the net flux of Na+, K+, Ca++ and Mg++. Following initial augmentation of instillate volume and H+ concentration, indomethacin caused sustained back diffusion of acid from lumen to mucosa; this was accompanied by mucosal bleeding. Peak effects of ASA on the net flux of ions occurred during or immediately after drug infusion and were greater than those of indomethacin and fenoprofen. Fenoprofen at 12.5 nM had no effect on concentrations of Ca++ and Mg++ while both were significantly increased by equal molar dose of ASA or indomethacin. In onset of action indomethacin was slow but once disruption of functional integrity started, it continued for hours showing no signs of returning to normal condition. In this sense, the total disruptive action of an equal weight or molar dose of indomethacin was greater than that of ASA or fenoprofen. At pH 1, the absorption of ASA from the Heidenhain pouch was greater than that of indomethacin and fenoprofen; their respective concentrations in the plasma were 53.9, 14.2 and 13.7 mumol.

Animals↗

Anti-Epstein-Barr virus antibody in patients with cancer of various sites and control groups.

Sera collected from patients with nasopharyngeal carcinoma (NPC, 321 cases), cancer of the other sites (297 cases), diseases of the ear, nose and throat (64 cases) and neighborhood controls matched for age and sex (817 cases) were titrated for antibodies to Epstein-Barr virus (EBV) by the indirect immunofluorescence antibody technique. High anti-EBV antibody titers (greater than or equal to 1:640) were noted in 55% in patients with NPC but only less than 31% were noted for the other 3 groups. The differences in the distributions of anti-EBV antibodies are statistically significant. The geometric mean levels of the antibody titers were 1:342 for the patients with NPC but less than 1:178 for the other 3 control groups. The relative risks shows that more than 40 times higher risk for those with equal to or higher than 1:640 antibody titers than those with lower than 1:40. The patients with NPC also show for higher ridit scales than the other 3 groups. The etiology of NPC was discussed with our findings.

Antibodies, Viral↗