Inflammatory gene signature in ulcerative colitis with cDNA macroarray analysis.

BACKGROUND: Most array analyses of ulcerative colitis have focused on identifying susceptibility genes for ulcerative colitis. AIM: To clarify the changes in gene expression during inflammation in ulcerative colitis colon mucosa using cDNA macroarray. METHODS: From 23 ulcerative colitis patients, 16 each of inflamed and non-inflamed specimens (total 32 samples for individual analysis) were obtained by colonoscopic biopsy. Eighteen of the 32 samples, used for pairwise analysis, consisted of nine sample pairs, each pair being from the same patient. We examined expression profiles of approximately 1300 genes with cDNA macroarray. Comparisons were made using two kinds of statistics, t-test and significance analysis of microarray in both analyses. The reproducibility of significant genes from the macroarray analysis was confirmed by real-time ploymerase chain reaction. RESULTS: We detected five upregulated genes, categorized into proinflammatory genes (MRP14, GRO gamma and SAA1) and anti-inflammatory genes (TIMP1 and Elafin) in inflamed mucosa, and one upregulated gene (L-FABP) in non-inflamed mucosa. CONCLUSIONS: As the cDNA macroarray analysis in this study exactly reflects the total profile of gene expression in the clinical setting of ulcerative colitis, the genes identified will be directly applicable to diagnostics or as novel therapeutic targets in active ulcerative colitis.

Natural history of endometrial hyperplasia. Study of 77 patients.

Seventy-seven patients with endometrial hyperplasia, 48 with simple hyperplasia without atypia (SH), 17 with complex hyperplasia without atypia (CH), one with simple hyperplasia with atypia (SHA), and 11 with complex hyperplasia with atypia (CHA) were prospectively followed-up by total curettage every 12 months for 3 years. Progression to carcinoma occurred in only one of the 77 patients; she showed grade 1 adenocarcinoma. The overall regression rates were 79% for SH, 100% for SHA, 94% for CH, and 55% for CHA, respectively. In patients with CHA whose disease reverted to normal endometrium, regression was most likely to occur within the first year.

Familial amyotrophic lateral sclerosis and parkinsonism-dementia complex of the Kii Peninsula of Japan: clinical and neuropathological study and tau analysis.

We report the first case of neuropathologically verified parkinsonism-dementia complex of the Kii peninsula, together with the patient's brother, who had amyotrophic lateral sclerosis. The propositus woman developed parkinsonism and dementia at 63 years of age and died at 70 without displaying clinical features of amyotrophic lateral sclerosis. The brain exhibited marked atrophy of the frontal and temporal lobes. Microscopically, there were many neurofibrillary tangles in the central nervous system, most markedly in the mesial temporal lobe and deep nuclei, as well as changes of amyotrophic lateral sclerosis but no senile plaques or Lewy bodies. Neurofibrillary tangles exhibited twisted tubule structures on electon microscopic examination, and an analysis of insoluble tau protein extracted from the fresh brain revealed a 60-, 64-, 68-kD triplet. The tau gene exhibited no mutations. Her brother developed progressive bulbar palsy-type amyotrophic lateral sclerosis at 45 years of age and died at 49 without presenting with dementia or parkinsonism. Neuropathological examination revealed not only pathologic features of amyotrophic lateral sclerosis but also a moderate number of neurofibrillary tangles in the temporal cortex and deep nuclei. The siblings were neuropathologically similar despite their different clinical manifestations. These findings suggest that amyotrophic lateral sclerosis and parkinsonism-dementia complex of this family may be phenotypic variants of a tauopathy caused by genetic abnormalities.

Clinical value of dilatation and curettage for abnormal uterine bleeding.

Dilatation and curettage was performed under anesthesia in outpatients in 1,837 patients aged over 26 with a history of abnormal uterine bleeding not associated with pregnancy or ovulation. Fifty-one (2.8%) patients were found to have malignant disease. Of these, 47 patients had endometrial carcinoma. An additional 111 (6.0%) patients were found to have endometrial hyperplasia. The incidence of either malignant disease or endometrial hyperplasia was 9.7% in patients over the age of 40. Complications of this method were noted in 12 (0.7%) patients; only three patients needed to stay in hospital.

A case of mixed acinar-endocrine carcinoma of the pancreas discovered in an asymptomatic subject.

A 50-yr-old Japanese man was found to have a hypoechoic mass 3 cm in diameter in the pancreatic head on an ultrasonography (US) examination without symptoms. A computed tomography (CT) scan demonstrated a 3-cm solid mass in the pancreatic head, and it was more clearly delineated as a low-density area on enhanced CT. Angiography showed a tumorlike stain, 3 cm in size, in the pancreatic head. The preoperative diagnosis was "special type of pancreatic tumor such as acinar cell carcinoma or non-functioning islet cell tumor." The patient was treated by pylorus-preserving pancreatoduodenectomy. Histological, immunohistochemical, and electron-microscopic studies of the surgical specimen led to a definitive diagnosis of a mixed acinar-endocrine carcinoma. The patient is currently well, with no signs of tumor recurrence, 18 mo after the operation. Our search of the Japanese and English-language literature retrieved only 15 well-documented cases of mixed acinar-endocrine carcinoma. Imaging in the reported cases revealed features of either acinar cell carcinoma or islet cell tumor, or both, which can may be detected even in small tumors more easily than conventional invasive ductal carcinoma of the pancreas because the detectability of this rare tumor on US and CT seems to be good.

[Weekly low-dose CPT-11 and HCFU for advanced colorectal cancer on an outpatient treatment basis].

We attempted a new outpatient treatment using weekly low-dose CPT-11 for advanced colorectal cancer patients. A 73-year-old female with para-aortic lymph node metastases from advanced rectal cancer was given outpatient treatment for more than 5 months with weekly low-dose CPT-11 and HCFU. CPT-11 was given intravenously at a dose of 20 mg/m2 on day 1 every week. On days 2-7, she was treated by oral administration of HCFU (600 mg). Her serum CEA level decreased and continued to do so for more than 5 months. The size of the para-aortic lymph node was reduced by approximately 40%. There were no adverse effects except leukopenia (grade 2). These results suggest that weekly low-dose CPT-11 and oral HCFU may be an effective therapy on an outpatient basis in cases of advanced colorectal cancer.

Hepatocellular carcinoma complicated by gastrointestinal hemorrhage caused by direct tumor invasion of stomach.

A 65-year-old man with multiple hepatocellular carcinoma (HCC) underwent intra-hepato-arterial chemotherapy (IHAC) through an implantable port over a period of 10 months after transcatheter arterial embolization (TAE) had been performed three times. TAE was performed twice more, and radiotherapy (total dose, 30 Gy; given over a 3-week period) was given for progressive disease in the lateral segment of the liver. Three months after the radiotherapy had finished, the patient suddenly developed melena. Diagnostic imaging revealed gastrointestinal (GI) hemorrhage from HCC invading the stomach, and total gastrectomy and lateral segmentectomy of the liver were performed because the bleeding could not be controlled. The resected specimen disclosed a centrally necrotic tumor that had invaded the lesser gastric curvature and perforated into the lumen. Pathology examination revealed that the HCC had expansively invaded the gastric mucosa, resulting in exposure in the lumen. The possible mechanisms of direct GI invasion by HCC are briefly discussed, with a review of the literature. GI bleeding secondary to involvement by HCC is rare. The enteric radiation injury seems to have been largely responsible for the GI bleeding in this patient.

[Quantitative X-ray computed tomography].

Quantitative X-ray Computed Tomography (QCT) has an advantage to be able to determine three-dimensional bone density of lumbar vertebral body compared with dual energy X-ray absorptiometry (DXA) method. We introduced the high reproductable QCT method as a simplified manual operation avoiding simultaneous imaging of both patients and bone mass phantoms. The coefficient of variation of values measured by phantom study was 0.6% for 7 years in our hospital. In measuring of 144 healthy Japanese women, the bone mineral density of lumbar spine was most likely to be decreased linealy with age.

Adenocarcinoma arising in a tailgut cyst: report of a case.

We report herein the unusual case of a 66-year-old woman found to have adenocarcinoma arising in a tailgut cyst. The patient had been observed for 6 months following the discovery of a presacral cystic mass measuring 10 x 9 cm for which she had refused surgery. The serum tumor marker, carcinoembryonic antigen, became slightly elevated, and diagnostic imaging distinctly revealed a tumorous lesion with papillary projection into the cyst lumen. The cystic mass was then excised through the transsacral approach. The pathological findings were compatible with moderately differentiated adenocarcinoma arising in a tailgut cyst. This entity is extremely rare, and only six cases, including our own, have been reported in the English literature. Early complete excision is advised because it is almost impossible to determine for certain whether presacral cystic masses are benign or malignant prior to surgery.

Gastric antral vascular ectasia causing severe anemia.

Gastric antral vascular ectasia (GAVE) that caused continuous gastrointestinal bleeding is reported in a 76-year-old woman who had been treated with repeated blood transfusions because of severe anemia. Endoscopic examination was performed and diffuse speckled telangiectasia of the entire antrum was observed. Laboratory data showed SGOT > SGPT, decreased chE level and the increased levels of serum gastrin and ICG at 15 min. Anti-HCV antibody was positive. Image examination revealed splenomegaly. There was no family history of telangiectasia, and no telangiectasia was found in other organs. The diagnosis was established as GAVE with liver cirrhosis. Surgical resection of the distal stomach resulted in termination of the bleeding, and the cirrhotic changes of the surface of the liver were revealed at that time, providing further evidence of liver cirrhosis. Although the pathogenesis of GAVE is unknown, liver cirrhosis and hypergastrinemia are thought to be associated with the condition. Importantly, this condition is a cause of severe gastrointestinal bleeding in elderly patients.

Focal nodular hyperplasia in an adolescent with glycogen storage disease type I with mesocaval shunt operation in childhood: a case report and review of the literature.

As patients with glycogen storage disease type I survive longer, cases with hepatic tumor have been increasingly documented. A 16 year old boy with glycogen storage disease type I was evaluated for multiple liver tumors. He was diagnosed on clinical features at 9 months of age and underwent a mesocaval shunt operation at 5 years of age. The biopsy of one of the masses showed focal nodular hyperplasia. This is uncommon in patients with glycogen storage disease type I, compared to those with adenoma or malignant hepatic tumor. The association of a portacaval shunt with focal nodular hyperplasia is significant compared to other tumors. An environment of high estrogen concentration or sex hormone binding globulin accompanied by shunt operation may cause focal nodular hyperplasia to develop in the liver of patients with glycogen storage disease type I.

[Inhalant abusers and psychiatric symptoms].

There are different opinions about the cause of chronic psychiatric symptoms observed in drug abusers between Japanese and foreign psychiatrists. The Japanese seem to recognize the chronic psychosis as the result of drug abuse. In the other hand, foreigners diagnose these cases as dual diagnosis of drug abuse and psychosis. Authors studied the problem in this research. One of the authors has examined 120 inhalant abusers of all, in- and out-patients in Kanagawa Prefectural Center of Psychiatry, Serigaya Hospital from 1991 to 1995. These patients were classified into three groups: psychosis group (23 patients), dependence group (51 patients) and abuse group (46 patients) according to their clinical courses and psychiatric symptoms. The psychosis group consists of patients who showed psychiatric symptoms such as hallucination, delusion and thought disturbance for long time after detoxification. The dependence group contains patients whose inhalant dependence was severe and met DSM-4 Diagnostic Criteria for Substance Dependence, but manifested no chronic psychiatric symptoms after detoxification. The patients belonging to abuse group were at the earlier stages of inhalant abuse and had no chronic psychiatric symptoms. The average age of the first inhalant abuse was 14.7 years old in the psychosis group, 14.8 years in the dependence group and 14.7 years in the abuse group. The average years of abuse was 9.0 years in the psychosis group, and 8.5 years in the dependence group. There was little difference between these two groups. The psychosis patients manifested chronic symptoms 5.7 years on average after the first abuse of inhalants. About one forth (26.1%) of the psychosis patients and only 5.9% of the dependence patients had family history of schizophrenia. The difference was statistically significant. These results suggest that chronic psychiatric symptoms are caused not only by inhalant abuse, but also by the genetic factors of psychosis of each patient. There have been several reports that many patients with dual diagnosis of substance dependence and other mental disorders are poly-drug abusers. In our study, 43.4% of the psychosis group patients and 19.6% of the dependence group patients had the past history of abuse of other drugs including methamphetamine and marijuana. The difference was, however, not statistically significant.

Lansoprazole versus lansoprazole plus amoxicillin treatment for eradication of Helicobacter pylori in patients with gastric ulcer.

Helicobacter pylori is a major cause of gastritis and an important factor in duodenal ulcer relapse. Eradication of H. pylori has usually been achieved by triple therapy, a combination of bismuth salts and two antibiotics. The disadvantage of these regimens is the large number of tablets and the high incidence of side effects. A new H+,K(+)-ATPase inhibitor, lansoprazole (LPZ), has a strong acid inhibitory effect and an anti-H. pylori effect in vitro. These dual effects have an advantage for the eradication of H. pylori by LPZ alone or by a combination of LPZ and antibiotics. In this study, we investigated an anti-H. pylori effect of LPZ alone and LPZ plus low-dose amoxicillin and the relation between the status of H. pylori colonization and the endoscopic healing stage. LPZ monotherapy suppressed H. pylori but did not eradicate it. LPZ plus low-dose amoxicillin dual therapy eradicated H. pylori in 45.5% of patients with gastric ulcer disease. However, this rate is not satisfactory for eradication therapy. The optimal dosage and duration of treatment need to be specified. A high rate of healing to the endoscopic S2 stage was achieved by eradication of H. pylori and the recurrence of gastric ulcer was suppressed in patients in whom H. pylori was eradicated. The eradication of H. pylori may change the natural course of gastric ulcer disease as it does in duodenal ulcer disease.

Mucosal immune response to Helicobacter pylori and cytotoxic mechanism.

BACKGROUND: Helicobacter pylori is widely accepted as a major pathogen in gastritis. The histologic features of H. pylori gastritis are the numerous infiltrating mononuclear cells (MNCs) and neutrophils. It is not clear what role the infiltrating MNCs and neutrophils play in H. pylori gastritis. METHODS: In this study, we have established enzyme-linked immunospot (ELISPOT) assay for the measurement of H. pylori antibody-producing cells in gastric mucosa. RESULTS: Using ELISPOT assay, we found that H. pylori-specific IgA-producing cells as well as IgG-producing cells were distributed in gastric mucosa. These H. pylori-specific antibodies in gastric mucosa and neutrophils are responsible for the induction of cytotoxic effect to cultured Vero cells. CONCLUSIONS: These observations suggest that a mucosal immune response specific to H. pylori is closely associated with the pathogenesis of gastritis.