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Biomedical subjects

K Hirata

Publications and source records attributed to K Hirata.

At least 343 records · Page 19Linked to original sources
PubMed1998

Alteration of expression of liver-enriched transcription factors in the transition between growth and differentiation of primary cultured rat hepatocytes.

In the present study, we showed the role of the liver-enriched transcription factors in the transition during which proliferating hepatocytes become quiescent. We used primary rat hepatocytes cultured in modified L-15 medium. The cells proliferated and, after the addition of 2% dimethyl sulfoxide (DMSO) from day 4, they stopped growing and gradually differentiated. During hepatic proliferation, expression of hepatocyte nuclear factors (HNF)1alpha, HNF4, C/EBP alpha, and C/EBP beta mRNAs was depressed, whereas that of HNF3alpha and HNF3beta transcripts was enhanced. After the addition of DMSO, the expression of HNF1alpha, HNF3gamma, and HNF4 returned to the level in isolated cells and HNF1beta mRNA expression gradually increased. However, expression of C/EBP alpha and C/EBP beta mRNAs was partially recovered. The mitoinhibitory agents, IL-1beta, IL-6, TGF-beta, and activin A, were examined to determine whether they could induce differentiation of proliferating hepatocytes as shown in cells treated with DMSO. Although these factors inhibited cell growth, the cells did not differentiate. The expression pattern of HNF3gamma mRNA was quite different in the cells cultured with DMSO and those cultured with cytokines. Therefore, hepatic differentiation requires not only inhibition of DNA synthesis but also induction of appropriate transcription factors. Thus, expression of HNF3gamma, C/EBP alpha, and C/EBP beta may be necessary for hepatocytes to acquire highly differentiated functions in addition to coexpression of certain amounts of transcripts of HNF1alpha, HNF1beta, HNF3alpha, HNF3beta, and HNF4 as well as suppression of C/EBP delta.

Animals↗
PubMed1998

N-glycolylneuraminic acid-containing GM1 is a new molecule for serum antibody in Guillain-Barré syndrome.

To clarify the pathogenesis of Guillain-Barré syndrome (GBS) after parenteral injections of bovine brain gangliosides, we searched for new molecules in bovine brain gangliosides recognized by sera from GBS patients. Gangliosides fractionated in a Q-Sepharose column were used as the antigens, and the binding of serum IgG or IgM was examined by thin-layer chromatography/immunostaining. Fourteen of 175 serum samples from the patients reacted with the monosialoganglioside fraction 2. In the neutral solvent system, a band in this fraction migrated with N-acetylneuraminic acid-containing GM1 [GM1(NeuAc)], whereas in the alkaline solvent system it migrated slower. This suggested that the band was N-glycolylneuraminic acid-containing GM1 [GM1(NeuGc)]. In both solvent systems, its mobility was almost the same as that of authentic GM1(NeuGc) from mouse liver. Secondary ion mass spectrometry showed that the ganglioside's structure was consistent with that of GM1(NeuGc). IgG anti-GM1(NeuGc) antibodies in sera from the GBS patients were significantly absorbed by GM1(NeuAc), indicative that the anti-GM1(NeuGc) antibodies cross-react with GM1(NeuAc). N-Glycolylneuraminic acid-containing gangliosides are so highly immunogenic in humans that the injection of GM1(NeuGc) could induce the production of IgG anti-GM1(NeuGc) antibody, which cross-reacts with GM1(NeuAc).

Animals↗
PubMed1998

Correlation between cytomegalovirus infection and IgM anti-MAG/SGPG antibody-associated neuropathy.

IgM anti-myelin-associated glycoprotein (anti-MAG)/sulfated glucuronyl paragloboside (SGPG) antibody is found in some patients with chronic polyneuropathy (CP). An antigen-driven process is considered to induce this autoantibody, but the agent has yet to be identified. It has been reported that sera from cytomegalovirus (CMV)-infected patients contained anti-SGPG antibody. To clarify the mechanism of the production of the anti-MAG/SGPG antibody, we investigated CMV DNA in sera from 26 patients with IgM anti-MAG/SGPG antibody-positive CP. Twenty-three (88%) had CMV DNA. The positive frequency was significantly higher than the frequencies in sera from patients with IgM anti-MAG/SGPG-negative CP, the other disease controls, and the normal control subjects. There were no statistical differences in the frequencies of Epstein-Barr virus DNA between anti-MAG/SGPG-positive and anti-MAG/SGPG-negative CP and between anti-MAG/SGPG-positive CP and each disease control. Moreover, no herpes simplex virus 1 DNA was detected in the sera from patients with anti-MAG/SGPG-positive CP. The strong correlation of anti-MAG/SGPG-positive CP with the presence of serum CMV DNA suggests that CMV infection induces the IgM anti-MAG/SGPG antibody.

Autoantibodies↗
PubMed1998

Prevention of small intestinal ischemia-reperfusion injury in rat by anti-cytokine-induced neutrophil chemoattractant monoclonal antibody.

The function of cytokine-induced neutrophil chemoattractant (CINC), which is the rat counterpart to human growth-related gene product belonging to the CXC chemokine subgroup, is based principally on neutrophil-specific chemotactic activity. In addition, we previously reported that plasma CINC was elevated during the period of small intestinal ischemia-reperfusion injury, and that there was a correlation between the degree of mucosal damage and the peak level of CINC after reperfusion, suggesting that CINC may play a major role in neutrophil infiltration into the rat small intestinal ischemia-reperfusion injury site. Thus, we investigated whether administration of anti-CINC monoclonal antibodies (mAbs) reduces small intestinal ischemia-reperfusion injury. Small intestine was subjected to ischemia for 3 h by occlusion of the anterior mesenteric artery with an atraumatic vascular clump. After infusion of anti-CINC mAbs or isotype-matched mAbs, the intestine was subjected to reperfusion. The pretreatment with anti-CINC mAbs attenuated ischemia-reperfusion injury in the small intestine, in association with the reduction of tumor necrosis factor-alpha and myeloperoxidase production, and resulted in the prolongation of survival. It is concluded that CINC plays an important role in the onset of rat small intestinal ischemia-reperfusion injury. In addition, blocking the action of CINC, namely, the neutrophil chemotactic activity, may be useful in preventing ischemia-reperfusion injury in the small intestine.

Animals↗
PubMed1998

Development of an ulcer in the side-to-side anastomosis of a jejunal pouch after proximal gastrectomy reconstructed by jejunal interposition: report of a case.

We present herein the first reported case of a deep ulceration developing in the pouch of a jejunal side-to-side anastomosis following the interposition of a jejunal U-shaped pouch (jejunal pouch), performed as reconstruction. A 47-year-old woman underwent a proximal gastrectomy and interposition of a jejunal pouch for early gastric cancer, 4 months after which she began to develop a fever. Esophagogastroscopy revealed a deep ulceration in the side-to-side anastomosis of the jejunal pouch. Her serum gastrin level was much higher than the normal range, and 24-h monitoring of the intraremnant stomach pH revealed that it was below 7.0 at night. A peptic ulcer was thought to be one of the causes of the pouchitis. Due to the drug-resistant ulceration and fever, a reoperation was performed, in which the jejunal pouch and remnant stomach were removed and Roux-en-Y reconstruction was done. There were no postoperative complications, and the fever resolved after surgery. Reconstruction of the jejunal pouch after proximal gastrectomy is recommended from the standpoint of quality of life (QOL); however, further studies on the size of the remnant stomach and the length of the interposed jejunal pouch are necessary.

Duodenal Ulcer↗
PubMed1998

Separate functions of alpha2beta1 and alpha3beta1 integrins in the metastatic process of human gastric carcinoma.

The expression of alpha2beta1 and alpha3beta1 integrins was studied immunohistochemically in 110 resected human gastric carcinomas. Formalin-fixed and paraffin-embedded samples were serially sectioned and stained with monoclonal antibodies specifically against the alpha2 and alpha3 subunits of beta1 integrins. Approximately 27% of the tumors expressed alpha2beta1 integrin, and 20% expressed alpha3beta1 integrin. The expression of alpha2beta1 integrin was associated with lymph node and liver metastases (P < 0.05 and P < 0.05, respectively), and the expression of alpha3beta1 integrin was associated with liver and peritoneal metastases (P < 0.005 and P < 0.0005, respectively). A multivariate analysis by the logistic regression model revealed that the expression of alpha2beta1 and/or alpha3beta1 integrins was an independent factor related to liver metastasis, and that the expression of alpha3beta1 integrin was as strong an influence on the formation of peritoneal metastases as the depth of invasion. The expression of alpha3beta1 integrin also correlated with increased invasiveness of the tumor; however, there was no correlation between alpha2beta1 integrin expression and the invasiveness. These results suggest that alpha2beta1 and alpha3beta1 integrins have separate influences on the metastatic properties of cancer cells.

Extracellular Matrix Proteins↗
PubMed1998

Increased expression of selectins in kidneys of patients with diabetic nephropathy.

In diabetic nephropathy leukocytes, mainly composed of monocytes/macrophages, which accumulate in the glomeruli and the interstitium, play an important part in the progression of glomerulosclerosis. The infiltration of leukocytes into inflammatory tissues or atherosclerotic lesions is mediated by adhesion molecules, which are expressed on the vascular endothelial cells, although little is known about the mechanism of leukocyte infiltration into diabetic renal tissues. P- and E-selectin are leukocyte adhesion molecules, which are expressed on the vascular endothelial cells and promote the adhesion of leukocytes to the endothelium. We investigated the expression of P- and E-selectin in the kidney tissue of patients with diabetic nephropathy and compared it with that of patients with other glomerular diseases (minimal change nephrotic syndrome, membranous nephropathy, IgA nephropathy, mesangioproliferative glomerulonephritis, and lupus nephritis). Expression of P- and E-selectin were both significantly increased in the glomeruli and the interstitium of patients with diabetic nephropathy as compared with those with other glomerular diseases. P- and E-selectin were both expressed along the glomerular capillaries and the peritubular capillaries in the interstitium. Neither P- nor E-selectin were correlated with the number of infiltrated leukocytes in the glomeruli, however, interestingly the E-selectin expression on peritubular capillaries was correlated with the number of infiltrated CD14 positive cells in the interstitium. These results suggest that E-selectin may play a key role in leukocyte infiltration into the renal interstitium in patients with diabetic nephropathy.

Adolescent↗
PubMed1998

Lack of survival benefit of extended lymph node dissection for ductal adenocarcinoma of the head of the pancreas: retrospective multi-institutional analysis in Japan.

It has not been established that extended lymph node resection is necessary for ductal adenocarcinoma of the head of the pancreas. According to the general rules for the study of pancreatic cancer, a multiinstitutional, retrospective clinical study was undertaken to investigate the efficiency of extended lymph node dissection for this malignancy. Altogether 501 patients underwent resection of the pancreas between 1991 and 1994 at 77 medical facilities; the surgical procedures, staging, lymph node dissection, curability, and survival rate were analyzed retrospectively. Eighteen of the patients died within 30 postoperative days, leaving 483 patients to be studied. The resection was curative microscopically in 94 patients, resulting in a 3-year survival of 29%. Macroscopically curative resection resulted in a 3-year survival of 14%; noncurative resection produced a 3-year survival of 6%. Although extended lymph node dissection was performed on 38 patients in stage I, 42 patients in stage II, 206 patients in stage III, and 1 patient in stage IV, there was no improvement in survival when the results were compared to those seen after standard or palliative lymph node dissection. The extent of lymph node dissection has not affected the prognosis for ductal adenocarcinoma of the head of the pancreas at any stage of the course of the disease. Excessive lymph node dissection in advanced cases does not necessarily lead to a favorable prognosis. The patients who undergo a radical operation with an adequate lymph node dissection have longer survivals.

Adult↗
PubMed1998

Relationship between skin blood flow and sweating rate, and age related regional differences.

To examine the mechanisms and regional differences in the age-related decrement of skin blood flow, 11 young (age 20-25 years) and 10 older (age 64-76 years) men were exposed to a mild heat stress by immersing their feet and lower legs in water at 42 degrees C for 60 min, while they were sitting in near thermoneutral conditions [25 degrees C and 45% relative humidity (rh)]. During the equilibrium period (25 degrees C and 45% rh) before the heat test, no group differences were observed in rectal (Tre) and mean skin (Tsk) temperatures or mean arterial pressure (MAP). During passive heating, Tsk was significantly lower in the older men 20 min after commencing exposure (P<0.001), although there were similar increases in Tre in both groups. Exposure time and age did not affect MAP. The local sweating rate (m(sw)) and the percentage change in skin blood flow by laser Doppler flowmetry (%LDF) relative to baseline values on the chest, back, forearm and thigh were significantly lower in the older men (P<0.001), especially on the thigh. After starting the heat exposure, three temporal phases were observed in the relationship between %LDF and m(sw) at most sites in each subject. In phase A, %LDF increased but with no increase in m(sw). In phase B, m(sw) increased but with no secondary increase in %LDF. Finally, in phase C, there were proportional increases in %LDF and m(sw). The increase in %LDF in phase A was significantly lower on the forearm and thigh (P<0.05) for the older men, but not on the chest and back. In phase C, the slopes of the regression lines between %LDF and m(sw) were lower for the older men on the back (P<0.03), forearm (P = 0.08) and thigh (P<0.03), but not on the chest. These results would suggest that the age-related decrement in skin blood flow in response to passive heating may be due in part to a smaller release of vasoconstrictor tone and to less active vasodilatation once sweating begins. Regional differences exist in the impaired vasoconstriction and active vasodilatation systems.

Adult↗
PubMed1998

Biochemical modulation therapy for pancreatic cancer.

It is well known that the clinical course in most patients with advanced pancreatic cancer is not influenced substantially by chemotherapy and/or radiotherapy. However, new chemotherapy, based on the synergistic antitumor activities of 5-fluorouracil (5-FU) and cisplatin (CDDP) producing biochemical modulation in solid cancers diagnosed as adenocarcinoma, has recently been reported to be effective. In gastrointestinal cancers, the optimal concentrations of each drug and the duration of the anticancer effects, as well as adverse effects have been confirmed in pharmacodynamic studies. Our experience of this treatment for advanced pancreatic cancer (stage IV) indicates the usefulness of the antitumor effect in terms of both effect on the tumor size in unresectable patients and prognosis in resectable patients. These results were remarkable in patients diagnosed as stage IV b and/or curability C. Although there were adverse effects, none were severe. However, anything compromising the patient's quality of life must be prevented. Randomized prospective studies of the combination of 5-FU and CDDP are expected in the near future.

Adenocarcinoma↗
PubMed1998

Drug-induced pneumonitis caused by sulfamethoxazole, trimethoprim during treatment of Pneumocystis carinii pneumonia in a patient with refractory ulcerative colitis.

We recently treated a patient with intractable ulcerative colitis complicated with Pneumocystis carinii pneumonia in whom sulfamethoxazole/trimethoprim caused pneumonitis. The pneumonitis was difficult to differentiate from worsening of the infection or the appearance of another opportunistic infection. The patient's history of sulfasalazine (sulfonamide)-induced pneumonitis made diagnosis possible. The CD4/CD8 ratio of lymphocyte subsets in bronchoalveolar lavage fluid was decreased at the diagnosis of Pneumocystis carinii pneumonia and this ratio had increased when drug-induced pneumonitis was diagnosed. Topical administration of beclomethasone dipropionate by enema was a safe and effective for the treatment of such a compromised patient with active colitis.

Adult↗
PubMed1998

Downregulation of cytokine-induced neutrophil chemoattractant and prolongation of rat liver allograft survival by interleukin-10.

We investigated whether the administration of recombinant human interleukin-10 (rhIL-10) regulates the production of cytokine-induced neutrophil chemoattractant (CINC) and improves graft survival in rat orthotopic liver transplantation (OLTx). Allograft recipients received injections of rhIL-10 at doses of 2, 10, 20, or 50 micrograms/kg/day. The allograft recipients that received rhIL-10 at 10 or 20 micrograms/kg/day showed a slight but significant prolongation of graft survival to 13.0 +/- 0.4 and 13.8 +/- 0.3 days, respectively, compared with 9.6 +/- 0.2 days in untreated allografts. Conversely, the administration of high-dose rhIL-10 shortened the allograft survival. In the rhIL-10 treatment groups, the mean serum and tissue levels of CINC at every time point after OLTx were reduced significantly compared with those in the no-treatment group. The mean peak neutrophil counts in the peripheral circulation (PC) of the groups given rhIL-10 at 10, 20, or 50 micrograms/kg/day from the samples obtained 12h after reperfusion were decreased significantly compared with the no-treatment group. Furthermore, the mean peak neutrophil counts in the PC of the groups given rhIL-10 at 10 or 20 micrograms/kg/day from the samples obtained between postoperative days (PODs) 7 and 10 were decreased significantly compared with the no-treatment group. The magnitude of liver damage and leukocyte infiltration in the rhIL-10-treated allografts on PODs 1 and 7 was reduced compared with that of untreated allografts. Our data indicate that the administration of rhIL-10 downregulates CINC production during the period of reperfusion injury and acute cellular rejection after OLTx, and prolongs liver allograft survival, suggesting that IL-10 therapy is potentially beneficial in OLTx.

Animals↗
PubMed1998

Histological evaluation of the effects of intraarterial chemotherapy for advanced breast cancer: a long-term followup study with respect to the survival rate.

To evaluate the effects of intraarterial infusion chemotherapy (IAIC) for advanced breast cancer, we examined the grade of histological responses of preoperative IAIC on tumors at the time of operation and estimated the patients' prognoses for 19 years. IAIC was done preoperatively using timely epochal anticancer drugs on 105 patients with locally advanced (Stage IIIa, IIIb) and metastatic (Stage IV) breast cancer. The survival rate of the Stage IIIb patients who showed a good histological response (Grade IIb< or =) to IAIC was 68.1% for 5 years, and 62.4% for 10 years, respectively. This was in contrast to that of the patients classified as Stage IIIb who showed a poor histological response (Grade IIa> or =) to IAIC. On the other hand, there was no significant difference in the survival rates between the Stage IIIa and IV patients with good and poor histological responses to IAIC. However, the findings showed that a good histological response to IAIC reflected a prolonged survival while the Stage IIIb and IV patients acquired a "down clinical staging" by IAIC. These results strongly suggest that IAIC thus appears to be a useful modality in the multidisciplinary treatment of advanced breast cancer, especially for Stage IIIb patients.

Adult↗
PubMed1998

Hemobilia caused by a giant benign hemangioma of the liver: report of a case.

We report herein the extremely unusual case of a 39-year-old woman in whom a giant cavernous hemangioma caused hemobilia. Cavernous hemangioma is the most common benign neoplasm of the liver and rarely causes any clinical symptoms or signs, while hemobilia usually occurs secondary to accidental operative or iatrogenic trauma, vascular disease, inflammatory disorders, gallstones, or tumors of the liver. Although invasive or malignant hepatic tumors often result in a communication between the biliary tract and the blood vessels, only one case of hemobilia caused by a benign cavernous hemangioma has ever been reported, but with no details about the patient. Our patient presented to a local hospital with severe melena as the initial main symptom, where ligation of the right hepatic artery was performed. This failed to relieve her symptoms, and she was subsequently referred to our department where a right hepatectomy was performed. Histopathological examination revealed no malignancy combined with the tumor; however, the hemangioma was exposed to the bile duct in segment VIII, which was presumably the cause of the hemobilia. This patient remains in good health almost 6 years after her operation. To the best of our knowledge this is the first case report of hemobilia caused by a cavernous hemangioma, and is accompanied by a detailed analysis.

Adult↗
PubMed1998

Neuroendocrine carcinoma of the extrahepatic biliary tract with positive immunostaining for gastrin-releasing peptide: report of a case.

We report herein the first documented case of gastrin-releasing peptide-positive neuroendocrine (NE) carcinoma of the extrahepatic biliary tract. An invasive tumor measuring 2.5 x 1.5 cm was located in the confluence portion of the cystic duct in a 70-year-old Japanese man. Histologically, the tumor was found to be composed of small polygonal cells which formed a solid and trabecular structure, and the frequencies of both mitoses and small necrotic areas were dominant. The tumor cells were immunoreactive to the NE markers chromogranin-A and neuron-specific enolase, as well as to carcinoembryonic antigen and gastrin-releasing peptide. Although a few cases of gastrin-releasing peptide-positive small-cell lung carcinoma have been documented, there have been no reports of gastrin-releasing peptide-positive NE carcinoma occurring in the gastrointestinal tract. We consider our case not merely to be of pathological interest, but also to have clinical and therapeutic implications.

Aged↗
PubMed1998

High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families.

Mutations in either of two recently identified genes, BRCA1 and BRCA2, are thought to be responsible for approximately two-thirds of all cases of autosomal-dominantly inherited breast cancer. To examine the nature and frequency of BRCA1 and BRCA2 mutations in Japanese families exhibiting a high incidence of breast cancer, we screened 78 unrelated families in this category for mutations of these two genes. Examining the entire coding sequences as well as exon-intron boundaries of both genes by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and multiplex-SSCP analysis, we identified possible disease-causing alterations in BRCA1 among affected members of 15 families and in BRCA2 in another 14 families. In 15 of those 29 families, the affected individuals carried missense mutations, although most germline mutations reported worldwide have been deletions or nonsense mutations. Our results, indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over frameshifts or nonsense mutations in Japanese breast cancer families, will contribute significantly to an understanding of mammary tumorigenesis in Japan, and will be of vital importance for future genetic testing.

BRCA2 Protein↗