Case of Gastric Lymphoma Diagnosed by Laparoscopic Excision Biopsy

Primary gastric lymphoma is a relatively uncommon disease and sometimes forms submucosal growth causing difficulty of diagnosis. We have reported a case of primary gastric lymphoma successfully diagnosed by laparoscopic wedge resection, after repeatedly performing endoscopic forcep biopsies. Diagnostic laparoscopy for obtaining definite histological diagnosis can be regarded as minimally invasive, accurate and safe.     

Possible chemoresistance-related genes for gastric cancer detected by cDNA microarray

To identify chemoresistance-related genes of gastric cancer, we utilized cDNA microarray technology. Thirty-five gastric cancer specimens surgically resected at our institute between 1998 and 1999 were studied for quantification of expression of 6300 genes by means of oligonucleotide microarray methods, and the results were evaluated in comparison with the chemoresistance of the specimens, which was determined by MTT (tetrazolium-based 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Inhibition rates (IR) were determined for cisplatin (DDP), 5-fluorouracil (5-FU), mitomycin C or doxorubicin. IR of 60% or more was regarded as sensitive to each agent, and IR of less than 40% was defined as resistant. Clustering was successfully completed for DDP, resulting in selection of 23 candidates as DDP-resistance-related genes, including vascular permeability factor, 2 membrane transporting subunits, and retinoblastoma-binding protein-1. In addition, further selection of DDP-resistance-related genes was performed according to these criteria: 1) Expression of the gene can be detected in more than 70% of resistant tumors. 2) Expression can be detected in less than 30% of sensitive tumors. 3) Expression in tumors is more than twice that of normal mucosa in more than 50% of specimens. Then, metallothionein-IG and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were identified as candidate DDP-resistance-related genes. When known DDP-resistance-related genes were analyzed according to the MTT assay result, families of glutathione-S-transferase and cydooxygenase-2 genes were also evaluated as resistance-related genes. For 5-FU resistance, dihydropyrimidine dehydrogenase and HB-EGF-like growth factor genes were also suggested to be resistance-related genes. The present study demonstrated that oligonucleotide microarrays can provide information regarding chemoresistance factors in cancer. (Cancer Sci 2003; 94: 355–359)     

Cleavage of hepatocyte growth factor activator inhibitor-1 by membrane-type MMP-1 activates matriptase

Co-expression of membrane-type 1 (MT1)-MMP with hepatocyte growth factor activator inhibitor-1 (HAI-1) in HEK293T cells resulted in cleavage of HAI-1 to produce three fragments. Recombinant MT1-MMP was shown to cleave HAI-1 protein in vitro. Hepatocyte growth factor activator inhibitor-1 was initially identified as the cognate inhibitor of matriptase, a transmembrane serine protease that processes urokinase-type plasminogen activator (uPA). Co-expression of HAI-1 with matriptase suppressed matriptase protease activity, and co-expression of MT1-MMP with them resulted in recovery of matriptase activity by stimulating shedding of HAI-1 fragments. Matriptase protein was detected in squamous carcinoma-derived HSC-4 cells, however, matriptase protease activity was undetectable. Transfection of siRNA for HAI-1 enhanced serine protease activity, which was suppressed by cotransfection of matriptase siRNA. Collagen-gel culture or treatment with concanavalin A (ConA) of HSC-4 cells enhanced MT1-MMP activity, which induced shedding of HAI-1 fragments and conversely stimulated uPA activation by these cells. Serine protease activity, including uPA activation of cells treated with ConA, was abrogated by downregulation of either matriptase or MT1-MMP through the transfection of each siRNA. These results suggest that MT1-MMP induced by collagen-gel culture or ConA treatment causes cleavage and shedding of HAI-1 protein, which allows activation of matriptase in HSC-4 cells. HSC-4 cells showed a characteristic invasive growth by forming vacuole-like structures in collagen gel, which was suppressed by transfection of siRNA for either MT1-MMP or matriptase, suggesting that activation of matriptase through the cleavage of HAI-1 is one of the MT1-MMP multifunctions essential for invasive growth of HSC-4 cells.     

Mode of onset and two years outcome of a broad spectrum of affective disorders]

In recent years emphasis has tended to be placed on assessing and diagnosing low-grade affective disorders. If mild affective symptoms are also considered a broad spectrum of affective disorders, this spectrum can be seen, not only in the manifestation of major symptoms of such illnesses as manic-depressive illness, but also in symptoms of various mental disorders. The present study was undertaken to analyze the clinical features of a broad spectrum of affective disorders in a prospective follow-up study. Ninety mentally ill patients who visited our outpatient clinic were followed for 2 years, to investigate the mode of onset, the course and outcome of their disorders. Using a semistructured interview method specially developed for this survey, these patients were divided into a broad spectrum of affective disorder group and the other groups. Forty-nine patients were allocated to a spectrum of affective disorder group characterized by four-day (or longer) persistence of at least one of the following symptoms, depressed mood, loss of interest or elevated, expansive, or irritable mood. Of the forty-nine patients there were only two patients with manic symptoms. And the forty-seven patients with depressive symptoms were compared with the other groups as a main subject. The other groups were composed of eighteen patients with psychotic symptoms (the psychotic group) and 23 patients with neurotic symptoms (the neurotic group). The psychotic and neurotic groups did not satisfy the criteria shown above. There was no significant differences in male-to-female ratio or age between these three groups. When the mode of onset of symptoms were compared, the percentage of cases in whom symptoms could be identified early (within 10 days after onset) was 64.4% in the depressive group, 41.2% in the psychotic group and 30.4% in the neurotic group. The percentage of cases who remitted 2 years later was 70.2%, 38.9%, 45.5% in the depressive group, psychotic and neurotic groups, respectively. The GAS score (mean +/- SD), assessed 2 years later, was 76.2 +/- 12.5, 62.8 +/- 11.7, 78.2 +/- 9.9 points for these three groups, respectively. These results suggest that a broad spectrum of depressive disorders develops more acutely and patients with this spectrum are more likely to recover from symptoms and in function. Thus, the course of disorders was more favorable in the depressive group than in the psychotic group or the neurotic group.     

Possible neuronal mechanisms involved in neurotensin-induced catalepsy in mice

The neuronal mechanisms of neurotensin (NT)-induced catalepsy were investigated in mice. NT administered intracerebroventricularly (ICV 0.5, 1.0 and 2.0 g) produced catalepsy in a dose-dependent fashion. A significant effect was observed at 2.0 g and a maximal effect 2–3 h after injection. The NT-induced catalepsy was inhibited by pretreatment with atropine, trihexyphenidyl or biperiden (each drug, 0.8–5.0 mg/kg, IP), anticholinergic drugs, and L-DOPA (100, 200 mg/kg, IP). However, the catalepsy was not significantly antagonized by p-chlorphenylalanine (300 mg/kg×3 days, IP) or methysergide (5, 10 mg/kg, IP), antiserotonergic drugs, and was not potentiated by the GABAergic drugs, aminooxyacetic acid (25 mg/kg, IP) or muscimol (1 mg/kg, IP). In addition, the NT-induced catalepsy was dose-dependently reduced by antihistamines, such as diphenhydramine (0.8–10 mg/kg, IP) and tripelennamine (0.4–5.0 mg/kg, IP) and was potentiated after treatment with histidine (250, 500 mg/kg, IP), a precursor of brain histamine. NT-induced catalepsy was also reduced by ICV pretreatment with diphenhydramine (1–5 g/rat), a H₁ antagonist, but not by cimetidine (5, 20 g/rat), a H₂ antagonist. These findings suggest that the catalepsy induced by NT may involve not only central cholinergic and dopaminergic mechanisms but also a histaminergic mechanism mediated via H₁-histamine receptors, and seems to differ from the catalepsy induced by neuroleptics.     

Evaluation of acoustic radiation force impulse elastography for fibrosis staging of chronic liver disease: a pilot study

Background: Acoustic radiation force impulse (ARFI) is a new technology integrated into conventional B‐mode ultrasonography. ARFI is used to evaluate tissue stiffness in several organs, but this method has not been applied for liver fibrosis. Aim: The aim of this study was to determine whether ARFI elastography is useful for the evaluation of liver fibrosis. Methods: This study enrolled 55 consecutive patients with chronic liver disease who underwent a liver biopsy for histological assessment of liver fibrosis by the Metavir scoring system. Liver stiffness of the 55 patients and 25 healthy volunteers was evaluated by ARFI elastography and was expressed as the shear wave velocity. Cut‐off values were determined using receiver‐operating characteristic (ROC) curves. Results: Histological liver fibrosis was evaluated by Metavir scoring; F0: six cases, F1: 14 cases, F2: nine cases, F3: nine cases and F4: 17 cases. Liver stiffness determined by ARFI elastography was correlated with histological liver fibrosis (P<0.0001). The areas under the ROC curves were 0.94 (95% confidence intervals, 0.87–0.99) for F2–F4, 0.94 (0.88–0.99) for F3–F4 and 0.96 (0.91–1.01) for F4. The cut‐off values of the shear wave velocity were as follows: >1.34 m/s for F2–F4 (sensitivity 91.4%, specificity 80%); >1.44 m/s for F3–F4 (sensitivity 96.2%, specificity 79.3%); and >1.80 m/s for F4 (sensitivity 94.1%, specificity 86.8%). Conclusions: Ultrasonic ARFI elastography is a novel, non‐invasive and reliable method for the assessment of liver fibrosis in patients with chronic liver disease.     

Fatty liver with metabolic disorder,such as metabolic dysfunction‐associated fatty liver disease,indicates high risk for developing diabetes mellitus

IntroductionNonalcoholic fatty liver disease (NAFLD) is diagnosed after excluding other liver diseases. The pathogenesis of NAFLD when complicated by other liver diseases has not been established completely. Metabolic dysfunction‐associated fatty liver disease (MAFLD) involves more metabolic factors than NAFLD, regardless of complications with other diseases. This study aimed to clarify the effects of fatty liver occurring with metabolic disorders, such as MAFLD without diabetes mellitus (DM), on the development of DM.Materials and MethodsWe retrospectively assessed 9,459 participants who underwent two or more annual health check‐ups. The participants were divided into the MAFLD group (fatty liver disease with overweight/obesity or non‐overweight/obesity complicated by metabolic disorders), simple fatty liver group (fatty liver disease other than MAFLD group), metabolic disorder group (metabolic disorder without fatty liver disease), and normal group (all other participants).ResultsThe DM onset rates in the normal, simple fatty liver, metabolic disorder, and MAFLD groups were 0.51, 1.85, 2.52, and 7.36%, respectively. In the multivariate analysis, the MAFLD group showed a significantly higher risk of DM onset compared with other three groups (P < 0.01). Additionally, the risk of DM onset was significantly increased in fatty liver disease with overweight/obesity or pre‐diabetes (P < 0.01).ConclusionsFatty liver with metabolic disorders, such as MAFLD, can be used to identify patients with fatty liver disease who are at high risk of developing DM. Additionally, patients with fatty liver disease complicated with overweight/obesity or prediabetes are at an increased risk of DM onset and should receive more attention.