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L Fung

Publications and source records attributed to L Fung.

At least 19 recordsLinked to original sources
PubMed2004

Diagnostic comparison of three groups of examiners using visual and laser fluorescence methods to detect occlusal caries in vitro.

BACKGROUND: To evaluate the accuracy of the DIAGNOdent laser device (DD) for detecting occlusal fissure caries when used by three groups of examiners. METHODS: Three final-year dental students (S), three General Dental Practitioners (G), and three Academic Clinicians (A) individually examined the non-cavitated occlusal surfaces of 25 extracted permanent molars using visual inspection (VI) then DD assessments. The presence of caries was confirmed following tooth sectioning. A cut-off limit of 30 was used for the DD to avoid over-treatment in a low caries-risk situation. RESULTS: For VI, individual examiner sensitivity (caries correctly diagnosed) ranged from 53 to 86 per cent, and specificity (sound teeth correctly diagnosed) ranged from 76 to 95 per cent, with low Kappa agreements. Group S achieved the highest sensitivity (80 per cent) and Groups G and A achieved the highest specificities (88 per cent). For DD, individual examiner sensitivity ranged from 19DD, individual examiner sensificity ranged from 19 to 77 per cent, and specificity from 71 to 97 per cent, with generally moderate Kappa agreements. Group A achieved the highest (67 per cent) and Group G the lowest (44 per cent) sensitivities, and Group G achieved the highest specificity (94 per cent). CONCLUSIONS: There were similar widely varying results for the two diagnostic methods and for the three groups of examiners. However, the relatively high sensitivities found with VI and specificities found with DD should avoid over-treatment in low caries-risk populations.

Chi-Square Distribution↗
PubMed1999

Rapid renal single-photon emission tomography by continuous infusion of iridium-191m.

Continuous infusion of iridium-191m (t1/2 = 5 s), produced with an 191Os/191mIr generator, was used to obtain rapid high-resolution single-photon emission tomography (SPET) of renal blood flow in the rabbit. SPET scans of the abdomen were obtained with a triple-detector SPET system (MS3, Siemens Gammasonics). The generator was eluted at a flow rate of 3 ml/min, which delivered a steady-state dose of 170 MBq (4.5 mCi) of 191mIr. The total 191Os breakthrough was 850 kBq (23 microCi). A 5-min SPET acquisition recorded a total of 2.8 million counts, resulting in images of high technical quality. Volume-rendered images clearly showed the abdominal aorta, splenic artery, spleen, renal arteries, kidneys and splanchnic vasculature. Tomographic slices through the kidneys revealed tracer primarily within the renal cortices without visualization of the collecting system. The estimated effective dose equivalent for a 5 min infusion of 191mIr at a steady-state dose of 170 MBq is 0.74 mSv compared with 2.7 mSv from a 170 MBq dose of 99mTc-DMSA. This study demonstrates the feasibility of high-resolution SPET of regional renal perfusion in the rabbit by continuous intravenous infusion of 191mIr. The renal distribution of continuously infused 191mIr is largely within the cortices, with minimal or no detectable activity in the region of the renal pelvicalyceal system. Using this technique, cortical renal SPET can be completed much more rapidly (< 5 min) than with conventional renal cortical imaging agents, which suggests that this technique could be applied to the observation of rapid changes in renal perfusion such as those resulting from pharmacologic intervention, obviating the need for the patient to return for additional visits. Additional studies are required to (a) validate the methodology in larger animals prior to considering the potential for use in human beings, (b) optimize the generator design for continuous infusion, and (c) evaluate the changes in the distribution of 191mIr that occur in animal models of altered renal perfusion.

Animals↗
PubMed1999

The effect of dietary folate on Apc and p53 mutations in the dimethylhydrazine rat model of colorectal cancer.

Dietary inadequacy of folate enhances and folate supplementation suppresses colorectal carcinogenesis in the dimethylhydrazine rat model. Folate is an essential factor for DNA methylation and the de novo biosynthesis of nucleotides, aberrations of which play important roles in mutagenesis. This study investigated whether the mutational hot spots of the Apc and p53 genes for human colorectal cancer are mutated in dimethylhydrazine-induced colorectal neoplasms and whether dietary folate can modulate mutations in these regions. Rats were fed diets containing 0, 2 (basal requirement), 8 or 40 mg folate/kg diet. Five weeks after diet initiation, dimethylhydrazine was injected weekly for 15 weeks. Mutations were determined by direct sequencing in 11 low and seven high grade dysplasias and 13 invasive adenocarcinomas. A total of six Apc mutations were found in four dysplastic and carcinomatous lesions: two in two low grade dysplasias, two in one high grade dysplasia and two in one adenocarcinoma. All mutations were single base substitutions, four of which were A:T-->G:C transitions. Five of the six mutations were located upstream from the region corresponding to the human APC mutation cluster region. Dietary folate had no effect on the frequency and type of Apc mutations. No mutations were detected in exons 5-9 of the p53 gene in neoplastic lesions. These data suggest that in the dimethylhydrazine rat model of colorectal cancer, the Apc gene is mutated in early stages, albeit to a lesser degree than observed in human colorectal cancer, whereas the mutational hot spot of the p53 gene for human colorectal cancer is not commonly mutated. Although the low frequency of Apc mutations and the small number of neoplasms studied in this study might have precluded our ability to observe modulatory effects of folate, dietary folate appears to have no significant effect on Apc and p53 mutations.

Animals↗
PubMed1998

Ribavirin inhibits viral-induced macrophage production of TNF, IL-1, the procoagulant fgl2 prothrombinase and preserves Th1 cytokine production but inhibits Th2 cytokine response.

Ribavirin, a synthetic guanosine analogue, possesses a broad spectrum of activity against DNA and RNA viruses. It has been previously shown to attenuate the course of fulminant hepatitis in mice produced by murine hepatitis virus strain 3. We therefore studied the effects of ribavirin on murine hepatitis virus strain 3 replication, macrophage production of proinflammatory mediators including TNF, IL-1, and the procoagulant activity (PCA), fgl2 prothrombinase; and Th1/Th2 cytokine production. Although ribavirin had inhibitory effects on viral replication (<1 log), even at high concentrations complete eradication of the virus was not seen. In contrast, at physiologic concentrations (up to 500 microg/ml), ribavirin markedly reduced viral-induced parameters of macrophage activation. With ribavirin treatment, the concentrations of PCA, TNF-alpha and IL-1beta all decreased to basal concentrations: PCA from 941 +/- 80 to 34 +/- 11 mU/10(6) cells; TNF-alpha from 10.73 +/- 2.15 to 2.74 +/- 0.93 ng/ml; and IL-1beta from 155.91 +/- 22.62 to 5.74 +/- 0.70 pg/ml. The inhibitory effects of ribavirin were at the level of gene transcription as evidenced by Northern analysis. Both in vitro and in vivo, ribavirin inhibited the production of IL-4 by Th2 cells, whereas it did not diminish the production of IFN-gamma in Th1 cells. In contrast, ribavirin had no inhibitory effect on TNF-alpha and IL-1beta production in LPS-stimulated macrophages. These results suggest that the beneficial effects of ribavirin are mediated by inhibition of induction of macrophage proinflammatory cytokines and Th2 cytokines while preserving Th1 cytokines.

Animals↗
PubMed1998

Expression of the fgl2 and its protein product (prothrombinase) in tissues during murine hepatitis virus strain-3 (MHV-3) infection.

Murine Hepatitis Virus Strain 3 (MHV-3) produces fulminant hepatitis with 80-90% mortality in Balb/cJ mice. Previous studies in our laboratory have shown that peritoneal macrophages from MHV-3 infected mice produce a procoagulant (PCA) which has the ability to cleave prothrombin to thrombin (prothrombinase) encoded by the gene fgl2 located on chromosome 5. PCA accounts for sinusoidal thrombosis and hepatic necrosis and the necrosis and mortality can be prevented by treatment of animals with a monoclonal antibody to PCA. These present studies were designed to examine the expression of this gene (mRNA by Northern analysis and in situ hybridization) and the gene product PCA (immunochemistry) in tissues recovered from MHV-3 infected Balb/cJ mice in an attempt to explain the liver specific nature of MHV-3 disease. Fgl2 gene expression was detected as early as 8 hours after MHV-3 infection which persisted to 48 hours in the liver, spleen and lungs whereas no gene expression was seen in the brain or kidneys despite the fact that equivalent viral titers were detected in all tissues at all times. In the liver, fgl2 gene expression was confined to endothelial and Kupffer cells with no expression in hepatocytes. Immunochemistry localized the PCA protein to Kupffer cells and endothelial cells and necrotic foci within the liver. No PCA protein was detected by immunochemistry in any other tissues at any time during the course of MHV-3 infection. These results explain the liver specific nature (fulminant hepatitis) of MHV-3 infection and provides further evidence for the role of PCA in the pathogenesis of fulminant hepatitis. MHV-3 induces selective transcription of the gene fgl2 and only hepatic reticuloendothelial cells produce functional protein (PCA) which is known to account for fulminant hepatic failure produced by MHV-3.

Animals↗
PubMed1996

Dialysis adequacy and nutrition determine prognosis in continuous ambulatory peritoneal dialysis patients.

Peritoneal membrane function was assessed in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) using parameters derived from urea kinetic modeling and the peritoneal equilibration test (PET). Their relationships with other nutritional markers and overall morbidity were determined. Data regarding the patients' nutritional status as determined by total body nitrogen (TBN) measurements, hospital admissions, and infectious complications within the last 12 months were reviewed. Total dialysate clearance (Kt/V) delivered was highly dependent on residual renal function (P < 0.0001). Kt/V derived from peritoneal clearance diminished with increasing age (P < 0.05). A higher delivered total Kt/V was associated with higher normalized protein catabolic rates (P < 0.002), which in turn were associated with improved TBN (P < 0.05). Hospital admissions decreased with improved normalized protein catabolic rates (P < 0.05), and higher serum albumin and total protein levels (P < 0.01 and P < 0.002, respectively). Infectious complications correlated positively with time on dialysis (P < 0.01), and correlated negatively with TBN measurements (P = 0.05). No correlations were found between infectious complications and serum albumin level or peritoneal protein loss. However, the total duration of hospitalization was shortened with higher serum albumin and total protein levels (P < 0.0001 and P < 0.002, respectively). Although Kt/V determinations did not correlate with clearances determined by the PET, the PET-determined creatinine transport rate correlated with TBN (P < 0.05) but not with infectious complications. In conclusion, nutritional parameters correlate with outcome on continuous ambulatory peritoneal dialysis. An integral relationship exists between nutritional status and dialysis delivery, which is best assessed by urea kinetic modeling.

Aged↗
PubMed1995

MHV-3 induced prothrombinase is encoded by musfiblp.

Previously, we demonstrated induction of a unique macrophage prothrombinase, PCA, in MHV-3 infected BALB/cJ mice. By immunologic screening, a clone representing PCA was isolated from a cDNA library and sequenced. The sequence identified this clone as representing part of a gene, musfiblp, that encodes a fibrinogen-like protein. Six additional clones were isolated, and one clone, p11-3-1, encompassed the entire coding region of musfiblp. Murine macrophages did not constitutively express musfiblp, but when infected with MHV-3, synthesized musfiblp-specific mRNA. Musfiblp mRNA induction was earlier and significantly greater in BALB/cJ than A/J macrophages. Prothrombinase activity was demonstrate when musfiblp was expressed from p11-3-1 in RAW 264.7 cells. These data suggest that musfiblp encodes the MHV-induced prothrombinase.

Animals↗
PubMed1995

Distribution of drugs following controlled delivery to the brain interstitium.

Intracranial controlled release polymers have been used for drug delivery to the brain, bypassing the blood brain barrier (BBB). By understanding the rates and patterns of transport in the local tissues, it is possible to design delivery systems that provide the optimal spatial and temporal pattern of chemotherapy within the intracranial space. This paper reviews the kinetics of drug release from polymeric controlled release implants, and describes the fate of drug molecules following release into the brain interstitium. Potential improvements in drug delivery based on the understanding of the mechanisms of drug release, transport and elimination are discussed.

Animals↗
PubMed1995

Association of mouse fibrinogen-like protein with murine hepatitis virus-induced prothrombinase activity.

Previously, we demonstrated induction of a unique macrophage prothrombinase during infection of BALB/cJ mice by mouse hepatitis virus strain 3 (MHV-3). By immunologic screening, a clone representing this prothrombinase was isolated from a cDNA library and sequenced. The sequence identified this clone as representing part of a gene, musfiblp, that encodes a fibrinogen-like protein. Six additional clones were isolated, and one clone, p11-3-1, encompassed the entire coding region of musfiblp. Murine macrophages did not constitutively express musfiblp but, when infected with MHV-3, synthesized musfiblp-specific mRNA. musfiblp mRNA induction was earlier and significantly greater in BALB/cJ than A/J macrophages. Prothrombinase activity was demonstrated when musfiblp was expressed from p11-3-1 in RAW 264.7 cells. These data suggest that musfiblp encodes the MHV-induced prothrombinase.

Amino Acid Sequence↗
PubMed1995

Pattern of disease after murine hepatitis virus strain 3 infection correlates with macrophage activation and not viral replication.

Murine hepatitis virus strain (MHV-3) produces a strain-dependent pattern of disease which has been used as a model for fulminant viral hepatitis. This study was undertaken to examine whether there was a correlation between macrophage activation and susceptibility or resistance to MHV-3 infection. Peritoneal macrophages were isolated from resistant A/J and susceptible BALB/cJ mice and, following stimulation with MHV-3 or lipopolysaccharide (LPS), analyzed for transcription of mRNA and production of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), mouse fibrinogen-like protein (musfiblp), tissue factor (TF), leukotriene B4, and prostaglandin E2 (PGE2). Macrophages from BALB/cJ mice produced greater amounts of IL-1, TNF-alpha, TGF-beta, leukotriene B4, and musfiblp following MHV-3 infection than macrophages from resistant A/J mice, whereas in response to LPS, equivalent amounts of IL-1, TNF-alpha, TGF-beta, and TF were produced by macrophages from both strains of mice. Levels of mRNA of IL-1, TNF-alpha, and musfiblp were greater and more persistent in BALB/cJ than in A/J macrophages, whereas the levels and kinetics of IL-1, TNF-alpha, and TF mRNA following LPS stimulation were identical in macrophages from both strains of mice. Levels of production of PGE2 by MHV-3-stimulated macrophages from resistant and susceptible mice were equivalent; however, the time course for induction of PGE2, differed, but the total quantity of PGE2 produced was insufficient to inhibit induction of musfiblp, a procoagulant known to correlate with development of fulminant hepatic necrosis in susceptible mice. These results demonstrate marked differences in production of inflammatory mediators to MHV-3 infection in macrophages from resistant A/J and susceptible BALB/cJ mice, which may explain the marked hepatic necrosis and fibrin deposition and account for the lethality of MHV-3 in susceptible mice.

Animals↗
PubMed1995

Validity of conventional anthropometric techniques for predicting body composition in healthy Chinese adults.

There is little information on the application of generalized prediction equations to ethnic groups other than Europeans and groups of European descent. The purpose of this study was to crossvalidate conventional equations on a group of 56 Chinese adults. Body density was assessed by underwater weighing and also predicted by equations which use a combination of selected skinfolds-biceps, triceps, pectoral, subscapular, abdominal, suprailiac, thigh and calf. There were significant correlations (P < 0.01) between the various methods of predicting percentage fat. However, analysis of variance revealed significant differences (P < 0.01) between mean values. In the men, the Jackson and Pollock equation underestimated, and the Durnin and Womersley equation overestimated, the percentage fat predicted by underwater weighing. The best predictor site in this group was the medial calf skinfold (r = 0.81), which is not included in either equation. In the women, the best predictor sites were the triceps, suprailiac and thigh. As these sites are also used in the Jackson et al. equation, it is not surprising that there was no difference between the prediction of percentage fat by this equation and underwent weight. It is concluded that the Durnin and Womersley and Jackson and Pollock equations tend to overestimate and underestimate, respectively, the percentage fat in Chinese men. Alternative equations which use the calf skinfold may be more appropriate for this ethnic group. In Chinese women, there appears to be good agreement between Jackson and Pollock and hydrodensitometric estimations of percentage fat.

Adult↗
PubMed1995

Distribution of subcutaneous fat and equations for predicting percent body fat from skinfold measurements: a comparison between Chinese females from two age cohorts.

The need to apply different regression equations in predicting percent body fat was investigated with 40 Chinese females between 20-30 years and 40-50 years in Beijing in 1993-94. Skinfolds from 10 sites at subscapular, midaxillary, pectoral, abdominal, suprailiac, thigh, triceps, medial calf, suprapatellar, and forearm were measured with a Lange caliper. The criterion test was performed with hydrostatic weighing and the Siri equation was used to calculate percent body fat. It was found that there were significant differences in the distribution of subcutaneous fat between younger and older Chinese females, with the major differences in the abdominal and subscapular skinfolds. It also appeared that the 20-30 years cohort had a more evenly distributed subcutaneous fat that the 40-50 years cohort. A general prediction equation for percent body fat with skinfolds of the forearm, pectora, subscapular, and triceps was formulated with an R of 0.95 and SEE of 2.14. Separate equations were developed for the two age cohorts. These were found to be more accurate than the general equation. The present study indicated that subcutaneous fat distribution varied with age in the female and further study in this area would be needed to better understand the relationship between fat distribution patterns, metabolic risks, and cardiovascular disease.

Adipose Tissue↗
PubMed1994

Cholecystokinin type A receptors mediate intestinal fat-induced inhibition of acid secretion through somatostatin-14 in dogs.

This study was designed to examine whether one or both principle molecular forms of somatostatin (SLI), somatostatin-28 (S-28) and somatostatin-14 (S-14), mediate inhibition of stimulated gastric acid by intestinal fat and to determine whether the mode of action includes activation of type A cholecystokinin (CCK) receptors in conscious dogs. SLI molecular forms were separated by gel filtration chromatography after extraction of acidified plasma on octadecyl silyl cartridges and quantified by RIA. Basal plasma levels of S-28 and S-14 were 4.1 +/- 0.6 and 3.6 +/- 0.3 fmol/ml, respectively. Intraduodenal perfusion with a 10% fat emulsion increased plasma S-28 by 6.3 +/- 1.2 fmol/ml (P < 0.01) and S-14 by 17.8 +/- 2.6 fmol/ml (P < 0.001), and suppressed by 76 +/- 3% (P < 0.001) gastrin (150 pmol/kg.h)-stimulated gastric acid. Blockade of type A CCK receptors with MK-329 (75 micrograms/kg, i.v.) abolished S-28 and S-14 responses (both P < 0.001) and completely reversed the inhibitory effect of gastric acid produced by intraduodenal fat. Intravenous infusions of S-14 dose-dependently inhibited gastrin-stimulated secretion with an estimated 50% inhibitory dose of 125 pmol/kg.h that achieved an incremental plasma S-14 rise of 40 +/- 2 fmol/ml; infusions of S-28 at 30 pmol/kg.h increased plasma S-28 by 47 +/- 3 fmol/ml without altering acid output. The SLI antagonist cyclo-[7-aminoheptanoly-Phe-D-Trp-Lys-Thr(BZL)] (CyCam) reversed by 89 +/- 4% (P < 0.001) exogenous S-14-induced inhibition of gastrin-stimulated acid secretion, but did not influence gastric acid output after the infusion of S-28. CyCam also reversed by 139 +/- 9% (P < 0.001) the early phase of fat-induced acid inhibition; in the late phase, CyCam treatment was associated with a further 2-fold elevation of plasma peptide-YY (PYY) to 102 +/- 6 fmol/ml (P < 0.001) and a 75 +/- 5% suppression of gastric acid. Simulation of this plasma PYY increment with infusions of PYY at 50 pmol/kg.h inhibited by 44 +/- 5% gastrin-stimulated acid secretion. These results indicate that in conscious dogs, endogenous CCK mediation of intraintestinal fat-induced inhibition of stimulated acid secretion occurs in part through CCK type A receptor activation of S-14 secretion. Modulation of gastric acid by S-14 includes both inhibition and attenuation of further suppression via counterregulation of PYY secretion.

Amino Acid Sequence↗
PubMed1994

Changes in track and field performance with chronological aging.

Use of existing records to study performance decline with age has been recommended by several writers. This investigation attempts to identify one running, jumping, and throwing event whose performance was most affected by age. Results indicated that the 400 meter run and the long jump events were most affected by advancing age among both male and female master athletes whereas in the area of throws, the event most affected was the javelin for men and the discus for women.

Adult↗
PubMed1994

A Th1 cell line (3E9.1) from resistant A/J mice inhibits induction of macrophage procoagulant activity in vitro and protects against MHV-3 mortality in vivo.

Induction of immune coagulants has been implicated in the pathogenesis of murine hepatitis virus strain 3 (MHV-3)-induced fulminant hepatic necrosis. Previous work from our laboratory has shown that the induction of procoagulant activity (PCA) correlates with the resistance/susceptibility to disease in inbred and recombinant inbred (RI) strains of mice. Macrophages from susceptible, but not resistant, strains of mice expressed increased levels of PCA in response to MHV-3 stimulation. T lymphocytes, however, had a marked regulatory role in the final expression of macrophage PCA. CD3+ CD4+ CD8- lymphocytes from RI H-2 compatible susceptible mice were able to instruct macrophages from susceptible mice to express significantly augmented levels of PCA, whereas CD3+ lymphocytes from RI H-2 compatible MHV-3-immunized resistant mice were able to suppress induction of PCA. In this present study, T-cell lines were derived from draining popliteal lymph nodes from resistant A/J mice, which had been immunized with MHV-3. All T-cell lines showed marked proliferation to MHV-3 and MHV-JHM which was major histocompatibility complex (MHC) restricted. All cell lines were CD3+, four of these were CD4+ and one was CD8+. All of the CD4+ cell lines produced IL-2 and two produced interferon-gamma (IFN-gamma), consistent with the Th1 cytokine profile. One cell line (3E9.1) was able to inhibit the induction of macrophage PCA through production of a soluble factor although cell-to-cell contact could not be excluded. This CD4+ T-cell line conferred protection to infected and susceptible AXB8 mice. These results demonstrate that the existence of a Th1 subpopulation of cells with a regulatory effect on macrophage PCA induction in MHV-3-infected mice contributes to the resistance of the A/J strain of mice to MHV-3 infection.

Animals↗
PubMed1993

Regulation of somatostatin-14 and -28 secretion by gastric acid in dogs: differential role of cholecystokinin.

BACKGROUND: Prosomatostatin-derived peptides include two principle bioactive molecular forms, somatostatin 28 (S-28) and somatostatin 14 (S-14). This study examined whether there is a functional relationship between gastric acid secretion and the release of S-28 and S-14 into the circulation. METHODS: In conscious dogs with gastric and duodenal cannulas, S-28 and S-14 responses, measured after extraction of acidified plasma and separation by gel chromatography, were evaluated by administration of nutrients and acid-inducing secretagogues without and with omeprazole. RESULTS: Ingestion of a solid meal caused equivalent plasma elevations of S-28 and S-14, whereas infusions of histamine and gastrin selectively increased plasma S-14. Omeprazole decreased meal-stimulated S-28 (-67% +/- 8%; P < 0.01) and S-14 (-56 +/- 9%; P < 0.01) and abolished S-14 increases to histamine and gastrin. Intraduodenal perfusions of a liquid protein meal increased S-28 above S-14, comprising approximately 71% of total somatostatin-like immunoreactivity released, and omeprazole suppressed S-28 (-87% +/- 5%; P < 0.01) without influencing S-14. Similar responses occurred after exogenous cholecystokinin. Moreover, pretreatment of the intraduodenal protein meal with the cholecystokinin-A receptor antagonist MK-329 abolished increases of S-28 and S-14 and caused a further twofold increase of gastric acid (P < 0.025). CONCLUSIONS: In the fed state, gastric acid causes direct release of S-14 from the stomach, but the acid-dependent component of S-28 secretion requires cholecystokinin as a cofactor. Negative feedback regulation between somatostatin and gastric acid secretory responses to nutrients may include S-28 modulated, in part, by cholecystokinin.

Animals↗
PubMed1992

Influence of gastric acid on circulating somatostatin-14 and -28 released after insulin-induced hypoglycemia in conscious dogs.

Insulin hypoglycemia is a potent mechanism for somatostatin secretion into the circulation. Whether the associated increase in gastric acid mediates the rise of one or both principle molecular forms of somatostatin, somatostatin-14 (S-14) and somatostatin-28 (S-28), was examined in four conscious dogs. Somatostatin molecular forms were separated by gel filtration chromatography after extraction of acidified plasma on octadecyl silyl cartridges and quantified by RIA. Basal plasma levels of S-14 and S-28 were 3.4 +/- 0.2 and 4.1 +/- 0.6 fmol/ml, respectively. After hypoglycemia induced by insulin, plasma S-14 increased by 29.5 +/- 3.9 fmol/ml (P less than 0.001), and plasma S-28 increased by 7.2 +/- 0.9 fmol/ml (P less than 0.01). Suppression of hypoglycemia-mediated gastric acid secretion after the administration of omeprazole or ranitidine inhibited elevations of S-14 by 82 +/- 6% (P less than 0.001) and 81 +/- 7% (P less than 0.001), respectively, but had no effect on the rise of S-28. Atropine (50 micrograms/kg, iv), which also suppresses gastric acid secretion after insulin hypoglycemia, decreased S-14 by 59 +/- 3% (P less than 0.01) without influencing S-28. Atropine given after omeprazole treatment, however, increased S-14 levels observed after atropine (P less than 0.001) or omeprazole (P less than 0.001) alone and was equivalent to control levels. S-28 remained unaltered after atropine and omeprazole treatment. These results in conscious dogs indicate that after vagal stimulation induced by insulin hypoglycemia 1) both S-14 and S-28 are released into the circulation, but S-14 predominates; 2) gastric acid contributes directly to the stimulation of S-14, but not S-28, secretion; 3) muscarinic inhibitory mechanisms participate in the regulation of S-14 secretion, and this mechanism is amplified when vagally stimulated gastric acid secretion is suppressed; and 4) nonmuscarinic mechanisms mediate in part S-28 secretion. This study suggests the presence of a reciprocal functional relationship between gastric acid secretion and circulating S-14 that is mediated by vagal muscarinic mechanisms.

Animals↗