Hepatocyte apoptosis and cytosolic calcium dynamics in ischemic injury.
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Biomedical subjects
Publications and source records attributed to H Tajiri.
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myo-Inositol plays a role in many important aspects of cellular regulation including membrane structure, signal transduction and osmoregulation. It is taken up into the cells by the Na+ / myo-inositol cotransporter (SMIT). We investigated developmental changes in the expression of SMIT mRNA and protein in the rat. In the fetal rat brain, SMIT mRNA was abundantly and diffusely expressed throughout the whole brain and the spinal cord. Positive signals were expressed in neuronal and non-neuronal cells in these regions. SMIT is gradually down-regulated nearer birth, but intense signals were still detected in the brain at postnatal day one. In the adult rat brain, very weak hybridization signals were detected throughout whole brain except for the choroid plexus where SMIT mRNA expression remained high. In contrast, the pattern of developmental regulation of SMIT gene expression in the kidney was opposite to that seen in the brain. Signals in the kidney were very weak during embryonic stages, whereas SMIT expression increased significantly after birth. These results suggest that myo-inositol and its transporter play an important role in the CNS developmental stage.
BACKGROUND: Children with malignant disease who received multiple blood transfusions before the clinical definition of hepatitis C virus (HCV) require evaluation for HCV infection. STUDY DESIGN AND METHODS: The role of HCV infection in 54 children with primary malignant disease was evaluated in terms of the following aspects: prevalence of HCV infection, distribution of HCV subtype, the benefit of screening of blood donors, and the presence of chronic liver disease. The benefit of screening for HCV in a subset of patients who underwent bone marrow transplantation (BMT) was also evaluated. RESULTS: Seventeen patients (31.4%) of 54 tested were seropositive in a second-generation HCV antibody test. Thirteen patients (24.0%) were also positive for circulating HCV RNA. HCV subtype 1b and HCV subtype 2b were found in six and two patients, respectively. Multiple HCV genotypes were present in two patients. One of these two patients had relatively progressive liver disease. Before the introduction of blood screening with a second-generation HCV antibody test, 15 of 35 patients seroconverted, whereas none of 7 patients seroconverted after the screening was used (p = 0.032). For patients who underwent BMT, the screening drastically decreased the seroconversion rate, from 7 of 11 patients to 0 of 6 (p = 0.016). CONCLUSION: A considerable number of children with primary malignant disease who received multiple blood transfusions became infected by HCV before HCV screening was used. Patients who underwent BMT were at high risk for HCV infection. Screening with a second-generation HCV antibody test has proven to be remarkably beneficial in preventing HCV infection in these children.
Sequential endoscopic observation of dog colons was performed during colon carcinogenesis. Two beagle dogs were given suppositories containing N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) every day for five months. In month 3, aberrant crypt foci (ACF), a putative preneoplastic lesion, were found in the colons of both dogs, but not in an untreated dog. The frequency of ACF increased until month 10, and then decreased. In month 9, very small lesions, less than 1 mm in diameter, which were similar to human early flat tumors, were first noticed. One of these lesions grew to about 7 mm in size without a change in its shape for 10 months. There were more than ten flat-type tumors in the two dogs, but such lesions were not found in the untreated dog. By biopsy, two of the lesions were proved to be well-differentiated adenocarcinomas histologically. Four polypoid lesions were found in one of the carcinogen-treated dogs. Thus, flat-type adenocarcinomas were induced in the dog colon by ENNG, and their development was followed by magnifying endoscopy.
BACKGROUND: Hyperplastic polyps are common benign colorectal polyps, and are thought to have little association with malignant tumours in the colorectum. However, several reports suggest that some hyperplastic polyps may develop into colorectal neoplasms. AIM: To clarify genetic alterations in colorectal hyperplastic polyps. METHODS: Twenty eight colorectal polyps having serrated components were resected from patients endoscopically. The K-ras gene mutations in codons 12 and 13 were analysed by PCR-RFLP. Intranuclear p53 protein was immunostained by the avidin-biotin complex method. RESULTS: A mutation of the K-ras gene was detected in nine (47%) of 19 hyperplastic polyps, and five (56%) of nine adenomas. p53 protein nuclear accumulation was detected immunohistochemically in two (22%) of nine adenomas, but not in any of the hyperplastic polyps. CONCLUSION: Some hyperplastic polyps may be true neoplastic lesions, and could be precursors of malignant neoplasia.
A girl with severe growth retardation had the clinical features of Laron syndrome. Her serum insulin-like growth factor-I level was completely unresponsive to exogenous GH administration. The serum GH-binding protein (GHBP) level was below the detectable limit in the patient, but it was normal in her parents and brother. Her parents and brother were normal in their height. Amplification with PCR and direct sequencing of her GH receptor gene revealed compound heterozygous mutations. The allele from her mother contained a transversion of G to T in exon 7 that could introduce a stop codon in place of a glutamic acid at amino acid 224. Another mutation was found in the allele in her father and also identified in her brother. It was a C deletion at position 981 in exon 10 that could introduce a frame shift, thereby causing the production of 20 novel amino acids (310-329) instead of the wild-type sequence, the premature termination at codon 330, and the subsequent deletion of the C terminal portion of the intracellular domain. RT-PCR of her father's lymphocytes and sequencing of its complementary DNA revealed that only the wild-type GH receptor messenger RNA was expressed in his lymphocytes, though the mechanism remains unclear. These results suggest that neither of the mutant alleles could generate a functional GH receptor, which would be consistent with the patient's severe growth retardation and undetectable serum GHBP.
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A 60-year-old female patient with gastric cancer and lymph node and liver metastases was treated with a combination of tegafur and uracil (UFT) (375 mg/m2/day) and mitomycin C (MMC) (5 mg/m2 once weekly). On day 15, when diarrhea appeared, chemotherapy was stopped immediately. On day 21, the WBC decreased to 900/microl and high fever developed. Despite treatment with granulocyte colony-stimulating factor and antibiotics, leukopenia persisted and the patient went into septic shock on day 26. On day 34, WBC increased to 5,400/microl and she recovered, with reduction in the size of the lymph node and liver metastases. Pharmacokinetic examination after intravenous injection of low-dose MMC (0.5 mg/m2) showed a markedly high peak plasma concentration (PPC), a large area under the time-versus-concentration curve (AUC) and reduced clearance. Similarly, oral administration of UFT (tegafur 300 mg/body) produced a relatively higher PPC and a larger AUC of 5-fluorouracil (FU). The activity of dihydropyrimidine dehydrogenase, the rate-limiting enzyme in the metabolism of FU, in peripheral mononuclear cells was within the normal range (0.265 nmol/min/mg). MMC is believed to have played a large part in inducing the severe toxicity observed in this patient. Physicians should be aware of the possibility of severe toxicity during treatment with UFT and MMC, although details of its incidence and mechanism are unclear.
The case of a 68-yr-old woman with a rare type of Alonso-Lej's type III choledochal cyst (choledochocele) is described. This patient was admitted to the hospital because of right upper quadrant pain. Endoscopy revealed a bulge of the papilla of Vater resembling a submucosal tumor. Endoscopic retrograde cholangiopancreatography demonstrated cystic dilation of the terminal portion of the common bile duct. In addition, small stones were located in the gallbladder, the common bile duct, and the cystic lesion. Cholecystectomy, resection of the cystic lesion, and papilloplasty were performed. Histologically, the interior wall of the cyst was lined with biliary mucosa and demonstrated no evidence of malignancy. We reviewed 63 reported cases of choledochocele in Japan and 65 reported cases in the English literature. The clinical features of choledochoceles were similar in both groups, and they were associated with a minimal risk of malignant degeneration. These findings may have important implications for treatment.
We measured the maximal velocity of the blood flow in the main portal trunk by duplex Doppler ultrasound in children suffering from a variety of liver diseases. The maximal velocity of the main portal vein in children with chronic active hepatitis and liver cirrhosis was decreased significantly as compared to those in control children (p < 0.01). The maximal velocity of the main portal trunk and K indocyanine green (ICG) had no significant correlation (r = 0.25, n = 27). The patient with the lowest portal velocity had esophageal and gastric varices with red color sign. We conclude that the measurement of the maximal velocity of the main portal trunk with duplex Doppler ultrasound is useful in evaluating portal hypertension in children.
Endoscopic retrograde cholangiopancreatography was performed before laparoscopic cholecystectomy in 312 patients, with successful results in 287 patients (92.0%). Common bile duct stones were diagnosed in 26 of the 287 patients (9.1%). In eight of these patients, the diagnosis had not been suspected from the clinical or laboratory data or results of ultrasonography. Endoscopic sphincterotomy with stone removal was successful in all 23 patients who underwent this procedure. Anatomical variations were detected in 7 patients (2.4%), including origin of the cystic duct from the right hepatic duct and the accessory bile duct, and anomalous arrangement of the pancreaticobiliary ducts and choledochocele. Pancreaticobiliary malignancies were also diagnosed in 3 patients. The morbidity rate with diagnostic ERCP was only 0.7%. Preoperative ERCP proved highly useful and sale for determining biliary anatomy, and for detecting unsuspected stones or malignancies.
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Focal acinar cell dysplasia (FACD) was studied in 138 autopsied pancreases by multiple transsection examination and was found in 13 of the pancreases (9.4%). The average number of FACD per pancreas identified in our study was 5.7, ranging from 1 to 20, and the total number was 60. The location of FACD was 22 in head, 18 in body, and 20 in tail of the pancreas. FACD were rare lesions and found in only 41 of 2,819 slides (1.5%). The incidence of FACD seemed to be higher among males than among females, among patients with cancer in other sites than among those with no cancer, among diabetics than among nondiabetics, among heavy smokers than among nonsmokers, and among alcohol abusers than among abstainers. The males and heavy smokers had significantly more nodules of FACD per pancreas than females and nonsmokers. Simple and atypical hyperplasia of pancreatic ducts were found in 119 (86.2%) and 18 (13.0%), respectively. All pancreases with FACD had simple ductal hyperplasia. FACD and atypical ductal hyperplasia coexisted in one patient who had a history of heavy smoking, and this patient had the most nodules of FACD per pancreas among patients with FACD. No FACD was observed in pancreases without ductal hyperplasia. These findings suggested heavy cigarette smoking was one of the possible causes of FACD and ductal hyperplasia of pancreas.
We demonstrate immunoglobulin-complexed aspartate aminotransferase (macro-AST) in a 14-year-old boy with rectitis-type ulcerative colitis by using both gel filtration and electrophoresis methods. The immunoglobulin complexed with AST in this case was identified as an IgG kappa both by electrosyneresis and immunoprecipitation reactions. The present case was noted to have a concomitant elevation of macro-AST associated with deterioration of ulcerative colitis. However, macro-AST has continued to exist when the activity of ulcerative colitis subsided, and the serum level of AST became normal. Thus, macro-AST might be related to an immunological component of ulcerative colitis as well as to the activity of the disease.
We report the effective clinical use of endoscopic laser in Japan using the results of a nationwide survey and our own experience with more than 100 cases. The Nd:YAG laser and argon dye laser with hematoporphyrin derivative (photodynamic therapy) were most commonly used in digestive endoscopy and were investigated as new modalities of cancer therapy. Photodynamic therapy was fairly effective, especially in superficial esophageal cancer and the ill-defined lesions of early gastric cancer. Endoscopic laser treatment was carried out on 80 patients with 86 lesions of early gastric cancer at our hospital, and the following tumor types were proven highly curable by this means: focal cancer, IIa and so-called "gastritis-like" tumors less than 2 cm in size. The Nd:YAG laser provides a new approach to palliative treatment, such as recanalization of neoplastic obstruction in the advanced stage of gastrointestinal cancers.