Serovars, antimicrobial resistance and conjugative R plasmids of Salmonella isolated from human during the period of 1966-1986 in Tokyo. Research Group for Infectious Enteric Diseases

We examined 4,739 isolates of Salmonella isolated from patients with gastroenteritis during the period of 1966-1986 in Tokyo for the incidences of serovars, antibiotic resistance and conjugative R plasmids. The period of study was divided into three: 1966-73 (early period), 1974-79 (middle period), and 1980-86 (late period). The predominant serovars were S. typhimurium (34.3%), Infantis (5.6%), Panama (4.9%) in the middle period, S. typhimurium (31.7%), Paratyphi B (9.4%), Litchfield (7.3%) in the late period. These results were consistent with serovars of isolates from healthy citizens. The frequency of resistant isolates was as high as 86.9% in the early period, mostly streptomycin (SM)- and tetracycline (TC)-resistant isolates, but decreased significantly in the middle and the late periods, to 53.3 and 39.4%, respectively. The percentages of ampicillin (ABPC)-, chloramphenicol (CP)-, and kanamycin (KM)-resistant isolates increased in the late period. Strains carrying conjugative R plasmids were isolated as frequently as 57.8% of the total isolates in 1973, but as less frequently as 6.7% in 1981 indicating that the rate was roughly proportional to the incidence of the drug resistant isolates. The rate, however, increased gradually after 1981. The predominant resistance pattern of the R plasmids was TC-resistance in the early period, gradually changed into multiple and finally to AP-, CP-, KM-, SM-, TC- and sulfonamides-resistance in the late period.     

Microsatellite instability is rare in the clinical course of myelodysplastic syndrome studied with DNA from fresh and paraffin-embedded tissues

Microsatellite instability (MSI) has been reported to occur in various types of malignant neoplasms. We performed a polymerase-chain-reaction-based assay for MSI between the initial and the most recently available (“latest”) samples from 23 patients with myelodysplastic syndrome (MDS). Of these patients, 15 were informative at more than three microsatellite loci. Seven patients showed an increase in leukemic cells while 8 patients did not during the interval between the two analyses. Only 1 of the patients, who had refractory anemia with excess blasts, which changed to acute myelogenous leukemia, showed microsatellite alteration at the analysis times. Among all 23 patients, two alterations were detected in the 42 informative paired samples that showed an increase in leukemic cells (4.8%), while none was detected in the 59 paired samples without such an increase. In total, therefore only two alterations were detected among 101 informative paired samples (2%). This indicates that MSI is rare in the clinical course of MDS irrespective of disease status, and is consequently not a critical genetic event for disease progression in most MDS patients. Received: 26 November 1997 / Accepted: 15 January 1998     

Quantification of gastric ulcer healing by endoscopic ultrasonography

We studied and quantified the healing process of gastric ulcers in humans by means of endoscopic ultrasonography. Initially, using the water bath method, we scanned specimens of resected human stomachs with gastric ulcers including 9 open ulcers and 14 ulcer scars. Comparison of histological findings and measurement of the cross-section suggested that the ulcers observed in the ultrasonographic photographs were essentially equivalent to those in histological photographs. By using endoscopic ultrasonography, we then examined 16 patients with active, mainly recurrent, gastric ulcers before and after 2, 4, and 8 weeks of H2 blocker treatment, measuring the length and cross-sectional area of the ulcer in endoscopic ultrasonographic photographs. From measurements of the contraction rate of cross-sectional ulcer area during healing, we observed that the healed ulcers showed a relatively rapid rate of contraction in the first 4 weeks of therapy and the non-healed cases showed a poor contraction rate. Endoscopic ultrasonography is useful for the quantitative estimation of histological changes associated with gastric ulcer healing.     

Correlation of plasma concentrations of B-type natriuretic peptide with infarct size quantified by tomographic thallium-201 myocardial scintigraphy in asymptomatic patients with previous myocardial infarction.

BACKGROUND: Secretion of A-type (atrial) and B-type (brain) natriuretic peptides (ANP and BNP) increases in relation to left ventricular (LV) dysfunction in patients with myocardial infarction (MI). However, it is unknown what determines the concentrations of ANP and BNP in asymptomatic MI patients with preserved LV function, so the aim of the present study was to examine if they are associated with MI size. METHODS AND RESULTS: Plasma concentrations of ANP and BNP in the peripheral blood were measured in 88 asymptomatic (New York Heart Association class I) patients with previous MI. The infarct size was quantitatively calculated from rest thallium-201 myocardial single photon emission computed tomography. In multivariate linear regression analysis that included MI size, hemodynamic parameters, and age as covariables, only BNP concentrations had a significant association with MI size (p=0.0001). In contrast, ANP concentrations were not significantly correlated with MI size in either the univariate or multivariate analysis. CONCLUSIONS: BNP but not ANP concentrations increased in proportion to the scintigraphic MI size despite the lack of heart failure in asymptomatic patients with previous MI. Thus, the increase in plasma BNP concentrations reflects the MI size, an important determinant of prognosis, in asymptomatic patients with MI.     

Interaction of glucagon-like peptide-1(7-36) amide and gastric inhibitory polypeptide or cholecystokinin on insulin and glucagon secretion from the isolated perfused rat pancreas.

The interaction of three incretin candidates, glucagon-like peptide-1(7-36)amide (t-GLP-1), gastric inhibitory polypeptide (GIP), and sulfated COOH-terminal octapeptide of cholecystokinin (CCK-8-S), on insulin and glucagon release from the isolated perfused rat pancreas was studied. Under the perfusate condition of 8.3 mmol/L glucose, coinfusion of 0.1 nmol/L t-GLP-1 and 0.1 nmol/L GIP resulted in an augmented insulin release greater than that obtained by the same dose of each peptide alone. The degree of stimulation elicited by t-GLP-1 and GIP reached a plateau at 0.3 nmol/L for both infusates, and no cooperative effect was observed by coinfusion at 0.3 nmol/L. Coinfusion of 0.1 nmol/L t-GLP-1 and and 0.1 nmol/L CCK-8-S also resulted in an augmented insulin release greater than that obtained by the same dose of each peptide alone. A similar cooperative effect was observed by coinfusion at 0.3 nmol/L, 1 nmol/L, and 3 nmol/L. With the same perfusion experiments, glucagon release was not significantly affected by any peptide at concentrations of 0.1, 0.3, 1, or 3 nmol/L. The coinfusion of 1 nmol/L t-GLP-1 and GIP elicited a transient, but significant, increase in glucagon release. A similar result was obtained by the coinfusion of 0.3 nmol/L and 3 nmol/L t-GLP-1 and GIP, respectively. The coinfusion of t-GLP-1 and CCK-8-S did not affect the glucagon release.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aspartate aminotransferase-linked immunoglobulin complexes in serum of a patient with primary biliary cirrhosis

A 51-year-old woman who had been treated for primary biliary cirrhosis (PBC) was admitted to our hospital for evaluation of unexplained, isolated, persistently increased aspartate aminotransferase (AST) activity. Results of laboratory tests on admission showed: AST 171 KU, alanine aminotransferase 28 KU, and anti-mitochondrial titer 1/1280. Results of hepatitis B surface antigen (HBs Ag) and hepatitis C virus antibody (HCV Ab; C100-3) assays were negative. Histology of a liver biopsy specimen was compatible with a diagnosis of PBC (stage III of Scheuer's classificiation). The molecular size of serum AST was estimated to be more than 500 000 by high-performance size-exclusion liquid chromatography. Electrophoretic analysis showed an abnormal band of AST between supernatant AST (sAST) and mitochondrial AST (mAST), which band was characteristic of AST-immunoglobulin complexes (AST-Ig). Ouchterlony double-diffusion and immunoprecipitation tests identified the immunoglobulin component as IgM. The presence of AST-Ig appeared to be responsible for the elevated serum AST.     

TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome-positive leukemia cells

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) have been implicated in antitumor immunity and therapy. In the present study, we investigated the sensitivity of Philadelphia chromosome (Ph1)-positive leukemia cell lines to TRAIL- or FasL-induced cell death to explore the possible contribution of these molecules to immunotherapy against Ph1-positive leukemias. TRAIL, but not FasL, effectively induced apoptotic cell death in most of 5 chronic myelogenous leukemia-derived and 7 acute leukemia-derived Ph1-positive cell lines. The sensitivity to TRAIL was correlated with cell-surface expression of death-inducing receptors DR4 and/or DR5. The TRAIL-induced cell death was caspase-dependent and enhanced by nuclear factor kappa B inhibitors. Moreover, primary leukemia cells from Ph1-positive acute lymphoblastic leukemia patients were also sensitive to TRAIL, but not to FasL, depending on DR4/DR5 expression. Fas-associated death domain protein (FADD) and caspase-8, components of death-inducing signaling complex (DISC), as well as FLIP (FLICE [Fas-associating protein with death domain-like interleukin-1-converting enzyme]/caspase-8 inhibitory protein), a negative regulator of caspase-8, were expressed ubiquitously in Ph1-positive leukemia cell lines irrespective of their differential sensitivities to TRAIL and FasL. Notably, TRAIL could induce cell death in the Ph1-positive leukemia cell lines that were refractory to a BCR-ABL-specific tyrosine kinase inhibitor imatinib mesylate (STI571; Novartis Pharma, Basel, Switzerland). These results suggested the potential utility of recombinant TRAIL as a novel therapeutic agent and the possible contribution of endogenously expressed TRAIL to immunotherapy against Ph1-positive leukemias.     

Carcinoma of duodenal bulb arising from the Brunner’s gland

A 75-year-old man was diagnosed as having a sessile tumor measuring 1.4 x 1.0 cm in size in the duodenal bulb after upper gastroduodenal series. The biopsy specimens revealed a proliferation of the adenomatous glands showing an acinar structure with papillary infolding; type III mucus, which is characteristic of Brunner’s glands. Antral glands and mucus neck cells of the fundic glands were also observed in the adenomatous glands by concanavalin A staining. Thus, it was clear that the tumor had originated from the Brunner’s glands. Three years and four months later, the sessile tumor had developed into a fungating ulcerated tumor via a polypoid form. The biopsy specimens revealed a papillary adenocarcinoma with foci of undifferentiated carcinoma. Retrospectively, the adenomatous glands in the biopsy taken from the sessile tumor should have been regarded as low grade carcinoma. Therefore, we propose that when a polyp or tumor shows an increase in size or change in macroscopic appearance, surgery should be considered.     

Adenosine monophosphate-activated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression

Vascular smooth muscle cell (VSMC) proliferation is a critical event in the development and progression of vascular diseases, including atherosclerosis. We investigated whether the activation of adenosine monophosphate-activated protein kinase (AMPK) could suppress VSMC proliferation and inhibit cell cycle progression. Treatment of human aortic smooth muscle cells (HASMCs) or isolated rabbit aortas with the AMPK activator 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) induced phosphorylation of AMPK and acetyl Co-A carboxylase. AICAR significantly inhibited HASMC proliferation induced by both platelet-derived growth factor-BB (PDGF-BB) and fetal calf serum (FCS). Treatment with AICAR inhibited the phosphorylation of retinoblastoma gene product (Rb) induced by PDGF-BB or FCS, and increased the expression of cyclin-dependent kinase inhibitor p21(CIP) but not that of p27(KIP). Pharmacological inhibition of AMPK or overexpression of dominant negative-AMPK inhibited both the suppressive effect of AICAR on cell proliferation and the phosphorylation of Rb, suggesting that the effect of AICAR is mediated through the activation of AMPK. Cell cycle analysis in HASMCs showed that AICAR significantly increased cell population in G0/G1-phase and reduced that in S- and G2/M-phase, suggesting AICAR induced cell cycle arrest. AICAR increased both p53 protein and Ser-15 phosphorylated p53 in HASMCs, which were blocked by inhibition of AMPK. In isolated rabbit aortas, AICAR also increased Ser-15 phosphorylation and protein expression of p53 and inhibited Rb phosphorylation induced by FCS. These data suggest for the first time that AMPK suppresses VSMC proliferation via cell cycle regulation by p53 upregulation. Therefore, AMPK activation in VSMCs may be a therapoietic target for the prevention of vascular diseases.