Search PubMed⌕ Search

Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 307 records · Page 17Linked to original sources
PubMed1999

Detection of anti-LKM-1(anti-CYP2D6) by an enzyme-linked immunosorbent assay in adult patients with chronic liver diseases.

Anti-liver kidney microsome-1 (LKM-1) autoantibody, which is a serological marker for autoimmune hepatitis type II, recognizes Cytochrome P450 IID6 (CYP2D6). This autoantibody is also detected in a portion of patients with chronic hepatitis C. Anti-LKM-1 has been measured by indirect immunofluorescence (IF) using rat liver and kidney sections. However, this method has some problems in specificity and is so laborious to handle with many samples. In this study, in order to determine anti-LKM-1, we established an enzyme-linked immunosorbent assay (ELISA) for anti-CYP2D6 using a recombinant CYP2D6 fusion protein. We studied sera from 29 patients positive for anti-LKM-1 by the new ELISA. We further studied sera from a total of 301 patients with various liver diseases and 100 sera from normal controls negative for anti-LKM-1 by the new ELISA. The specificity of the ELISA was ascertained by absorption tests using sera positive for anti-LKM-1. In 29 sera from patients positive for anti-LKM-1 by IF, we found a good correlation between the logarithms of the antibody titers determined by IF and ELISA indexes obtained by our new method. Anti-CYP2D6 was positive in 12 of 12 (100%) patient with autoimmune hepatitis type II and 16 of 17(94.1%) with chronic hepatitis C positive for anti-LKM-1 by IF. In other 401 sera negative for anti-LKM-1 by IF, anti-CYP2D6 was all negative except a few sera. We established a new ELISA for anti-LKM-1 (anti-CYP2D6). This ELISA system is sensitive, antigen-specific and easy to be done. Therefore, this assay allows a routine test of many serum samples, especially for diagnosing autoimmune hepatitis type II.

Adult↗
PubMed1999

The apoptosis-inducing activity of the two protein phosphatase inhibitors, tautomycin and thyrsiferyl 23-acetate, is not due to the inhibition of protein phosphatases PP1 and PP2A (review).

Thyrsiferyl 23-acetate (TF-23A) has been shown to potently and specifically inhibit PP2A. TF-23A also induced a rapid cell death in various leukemic T- and B-cell lines. The TF-23A induced cell death with a typical apoptotic process. TF-23A and its several analogous compounds showed apoptosis-inducing activity. However, only TF-23A out of these compounds showed an inhibitory activity for PP2A. These results suggest that a portion of TF-23A involved in induction of apoptosis is different from that involved in the PP2A inhibition. Then, the effects of tautomycin and its derivatives on PP1 and PP2A and their apoptosis-inducing activity were examined. The C22-C26 moiety was essential for inhibition of protein phosphatase activity, whereas the C1-C18 moiety was essential for induction of apoptosis. Therefore, different moieties of tautomycin are involved in protein phosphatase inhibition and induction of apoptosis. From these results, it was concluded that the biological effects of phosphatase inhibitors are not necessarily induced by the inhibition of PP1 and PP2A but through other different molecular mechanisms which remain to be elucidated.

Animals↗
PubMed1999

Up-regulation of nuclear PP1alpha and PP1delta in hepatoma cells.

Activities of nuclear type 1 protein phosphatase (PP1) were significantly elevated in human HepG2 and rat AH13 hepatoma cells compared with primary cultured hepatocytes. We examined and compared the nuclear PP1 activities during the cell cycle between synchronized HepG2 cells and HGF-stimulated hepatocytes. Nuclear PP1 activity was significantly and more elevated at the G1/S transition in hepatoma cells compared with hepatocytes, although the amounts of PP1 isoforms remained constant. On the contrary, it was found that the basal levels of nuclear PP1 activity were significantly higher in hepatoma cells and that the amounts of PP1alpha and PP1delta were dramatically increased in the nuclear fraction of hepatoma cells.

Animals↗
PubMed1999

Inhibition of human small cell lung cancer cell growth by methylprednisolone.

Methylprednisolone (MP) inhibited cancer cell growth at concentrations between 0 and 2.0 mM. IC50 was 0.96 mM in H82, 0.44 mM in H345, 0.86 mM in H510A, 0.54 mM in N592 and 0.52 mM in H2081. The growth inhibition was not disturbed by addition of 1 microM RU38486. DNA fragmentation were observed in H510A and N592 at MP concentration of 0.2 mM. Glucocorticoid (GC) receptor mRNA expression was detectable only in H510A. We concluded that MP has potency as an anti-cancer agent at a high concentration. The effect was probably not through GC receptor binding, and growth inhibition was independent of apoptosis induction.

Binding, Competitive↗
PubMed1999

[A case of synchronous multifocal urothelial tumors in a patient with phenacetin abuse].

A 79-year-old male with phenacetin abuse was admitted to our University Hospital for treatment of asymptomatic gross hematuria. Intravenous urograpdy and computed tomography revealed synchronous right renal pelvic carcinoma and bladder carcinoma. Right nephroureterectomy and transurethral resection of bladder tumor (TUR-Bt) were performed. Histologically, right renal pelvic tumor and bladder tumor were both transitional cell carcinomas of grade 2, pT1, and grade 1 = 2, Ta, respectively. Additionally, pathological examination revealed two distal ureteral tumors, which were transitional cell carcinomas of grade 2, pTa. He also had a history of heavy tobacco-smoking (20 cigarettes per day for 50 years). We discuss the relationship between transitional cell carcinoma and phenacetin abuse as well as the influence of tobacco-smoking, and review the literature.

Aged↗
PubMed1999

Increased serum and urinary levels of a parathyroid hormone-related protein COOH terminus in non-small cell lung cancer patients.

Parathyroid hormone-related protein (PTHrP) is expressed in a variety of human cancers including lung cancer. Three mature peptides with different COOH-terminal regions, PTHrP (1-139), PTHrP (1-173), and PTHrP (1-141), are translated from three different mRNAs through alternative splicing. In each, COOH-terminal fragment (C-PTHrP) is stable and measurable in the urine. In the present study, we measured concentrations of circulating and urinary C-PTHrP in 28 patients with primary lung cancer and normal serum calcium levels. We used PCR to evaluate PTHrP mRNA expression and its alternative splicing types in 16 lung cancer cell lines and 17 lung cancer tissues. The average serum C-PTHrP level was 38.95 +/- 19.41 pmol/l in 28 lung cancer patients, whereas that in 10 normal subjects was 26.53 +/- 9.43; the difference was statistically significant (P = 0.0065). Average urine C-PTHrP:urine creatinine ratio was 7.56 +/- 5.17 x 10(-1) pmol/mg creatinine in 28 lung cancer patients, whereas it was 4.91 +/- 1.77 in 10 normal subjects; the difference was statistically significant (P = 0.0287). C-PTHrP radioimmunoassays detected that 23% of non-small cell lung cancer patients had higher serum C-PTHrP levels, and 32% had higher urinary C-PTHrP:urine creatinine ratio than average + 2 SD of normal subjects. Reverse transcription-PCR detected PTHrP mRNA expression in 21 of 21 non-small cell lung cancer (NSCLC) samples and 3 of 12 small cell lung cancer samples. In the cancer cell lines and tissues that had detectable PTHrP mRNA, PTHrP (1-139) mRNA was found in 21 of 24, PTHrP (1-173) mRNA was found in 19 of 24, and PTHrP (1-141) mRNA was found in 23 of 24. Our results suggest that all PTHrP mRNA expression is common in lung cancers. We found that NSCLCs cancers had detectable PTHrP mRNA, and serum and urinary C-PTHrP levels in NSCLC patients were significantly higher than those in normal subjects. We concluded that NSCLC produced PTHrP more frequently, but there was no clear significance of C-PTHrP measurement in lung cancer patients for cancer detection using the present assay. We suggested that PTHrP probably plays a role similar to a growth factor or proliferation factor in lung cancer, especially NSCLC, at a level insufficient to cause humoral hypercalcemia of malignancy.

Adenocarcinoma↗
PubMed1999

[Atypical neuroradiological features of microcystic meningioma: case report].

We report a rare case of microcystic meningioma presenting with atypical neuroradiological features. A 76-year-old woman was admitted to our hospital in October, 1996 because of head heaviness without obvious neurological deficits. Previous CT scan in 1989 revealed no abnormality, but a subsequent scan in 1992 showed a low-density area in the right frontal region. Since then the patient has been followed up as a case of cerebral infarction. At the time of the current admission, CT scan disclosed the low-density area as having grown to the size of 4 cm and heterogeneously enhanced after injection of contrast medium. On MRI the mass lesion was depicted as low-intensity on T1-weighted image and high-intensity on T2-weighted image. The mass was heterogeneously enhanced after administration of Gd-DTPA. Right internal and external carotid angiograms revealed neither tumor feeder nor tumor stain. Craniogram showed neither hyperostosis nor bone erosion, and yet bone scintigram demonstrated markedly increased uptake involving the right frontal bone near the tumor. At surgery the tumor was found to have originated from the dura in the right frontal convexity, which was well demarcated and separated from the surrounding brain tissue. Total removal designated as Simpson grade I procedure was accomplished. Light microscopy revealed abundant microcysts of varied size throughout the tumor tissue with the presence of whorl formation and psammoma body, but no malignancy was indicated. Electron microscopy further demonstrated interdigitation of the neighboring cell membranes, desmosomes, and intracytoplasmic filaments, which are pathognomonic findings of meningiomas. The microcysts were seen to reside in the extracellular spaces rather than in the cytoplasm. With these pathological findings, the tumor was finally diagnosed as microcystic meningioma.

Aged↗
PubMed1999

[Two cases of duodenal tuberculosis].

The present study described 2 cases of patients with duodenal tuberculosis. Case 1 was a 55 year-old Japanese male patient with pulmonary tuberculosis and past medical history of subtotal gastrectomy (Billroth II reconstruction). Tubercle bacilli were positive both on smear and culture from his sputum and feces. Because of complaining right hypochondralgia, upper gastrointestinal endoscopy was performed and revealed multiple ringed ulcers in the afferent limb of duodenum. Histopathological study of biopsy specimen demonstrated granulomatous inflammation as well as acid-fast bacilli confirmed by Ziehl-Neelsen staining. Tissue culture was positive for M. tuberculosis. Colonic tuberculosis was demonstrated by barium enema. Case 2 was a 45 year-old male patient with pulmonary tuberculosis in association with severe uncontrolled diabetes mellitus. Sputum polymerase chain reaction test was positive for M. tuberculosis. Granulomatous inflammation and positive acid-fast bacilli in biopsy specimen obtained from ulcers in the descending portion of the duodenum made a diagnosis of duodenal tuberculosis. No other intestinal tuberculous lesion was recognized. Since 1988, 11 cases of duodenal tuberculosis including the presented two cases have been reported in Japan. Most of the recent cases had tuberculous lesions in the descending portion of the duodenum and were diagnosed as duodenal tuberculosis by endoscopic examinations, while the majority of the cases reported before 1987 had tuberculosis in the more distant portions of the duodenum and were diagnosed mainly by surgical procedures.

Duodenal Diseases↗
PubMed1999

[Short- and long-term outcome after urethroplasty in the patients with hypospadias treated by Hodgson III method].

Between 1977 and 1997, 29 patients with hypospadias were surgically treated by Hodgson type III urethroplasty at Tsukuba University Hospital. The duration of surgery ranged from 150 to 535 minutes with an average of 269.3 minutes and the urethral catheter was removed between 4 and 14 days (average 8.7 day) after surgery. The postoperative hospital stay ranged from 10 to 29 days with an average of 18.4 days. The overall success rate of initial surgery was observed in 18 of the 29 patients (62.1%). As early postoperative complications, urethral fistula and stricture were seen in 10 (34%) and 3 (10%) patients, respectively; of these four fistulas persisted. As late complications revealed by questionnaire, erectile disorder was observed in one case. To obtain a higher success rate on initial treatment, skillful surgical technique and selection of appropriate cases are required.

Adolescent↗
PubMed1999

[Molecular biology in gastric cancer].

In gastric cancer, the process of carcinogenesis is thought to occur as a stepwise accumulation of genetic abnormalities. However, the mechanisms of the process of multistage carcinogenesis is still unknown for gastric cancer. Gene abnormalities seen in gastric cancer, including ras, myc, c-erbB-2, met, K-sam and cript are summarized herein. Abnormalities of cancer suppressor genes, including p53, RB and APC are also described. In our studies, the biological malignancy of patients with c-erbB-2 amplification was higher than that of patients without amplification. Moreover, the cases with amplification of c-erbB-2 were found to be highly correlated with distant organ metastasis. However, very little is currently known of the molecular abnormalities leading to gastric cancer. In order to clarify the multiple gene abnormalities in gastric cancer, we used the method of restriction landmark genomic scanning (RLGS). RLGS provides a useful method for genomic analysis of gastric cancer. In the future, new analytical methods that will permit screening of all gene abnormalities at once promise to improve our understanding of the mechanisms of gastric cancer.

Genes, erbB-2↗
PubMed1999

Lumbar spinal synovial cyst presenting with neurological deficit. A case report and review of the literature.

A spinal synovial cyst is a rare condition. We reported a case of lumbar spinal synovial cyst presenting neurological deficit. A 78-year-old woman was admitted to our hospital with the low back pain radiating to the left buttock. A myelography with computed tomography and magnetic resonance imaging revealed an extradural cystic lesion at the L5 and S1 level. At the time of surgery, a standard posterior approach was used to expose the posterior elements from L5 to S1. An en bloc laminectomy and total removal of the cyst was performed at the L5 to S1 level. The postoperative recovery was uneventful except for a slight pain in the left leg which persisted for some time.

Aged↗
PubMed1999

Intraoperative stress experienced by surgeons and assistants.

BACKGROUND AND OBJECTIVE: To determine the intraoperative stress on surgeons and assistants during cataract surgery, 12 surgeons and 3 assisting nurses were assessed based on their level of professional experience. METHODS: Surgeons were classified as inexperienced, intermediate, or experienced. Nurse assistants were classified as inexperienced or experienced. The intraoperative heart rates and urine adrenaline levels of each participant were measured. RESULTS: Inexperienced surgeons and nurse assistants had the highest heart rates at the beginning of surgery, and the rates tended to decrease toward the end of surgery. All values were higher than the other two groups throughout surgery. In surgeons with intermediate experience, the heart rates were not as high as in the inexperienced personnel; however, the heart rates were high throughout the surgery. The heart rate in one intermediate surgeon was markedly increased when a surgery was simultaneously broadcast on closed-circuit television. In experienced surgeons and a nurse assistant, the measurements increased slightly. CONCLUSIONS: The variations in heart rates and urine adrenaline levels showed characteristic patterns based on the experience of the surgical personnel.

Adult↗
PubMed1998

Antiemetic effects of sendide, a peptide tachykinin NK1 receptor antagonist, in the ferret.

The antiemetic activity of sendide, a new peptide tachykinin NK1 receptor antagonist, against cisplatin-induced emesis was investigated using ferrets. The frequency of cisplatin (10 mg/kg, i.p.)-induced retching (104.6 +/- 14.3/6 h) and vomiting (19.0 +/- 3.0/6 h) was significantly reduced by pretreatment with sendide (3.0 mg/kg, s.c.) (14.0 +/- 8.1/6 h and 1.8 +/- 1.2/6 h, respectively). Intravenous bolus injection of substance P (1-10 microg/kg) or 5-hydroxytryptamine (5-HT) (10-50 microg/kg) produced a dose-dependent increase in the abdominal afferent vagus nerve activity. The change from pre-injection level in the afferent nerve activity induced by substance P (1 microg/kg, i.v.) (453.7 +/- 51.5%) was significantly reduced by pretreatment with either sendide (100 microg/kg, i.v.) (276.1 +/- 50.1%, P < 0.05) or granisetron, a 5-HT3 receptor antagonist (1 mg/kg, i.v.) (146.3 +/- 14.0%, P < 0.01). The amount of 5-HT released into the solution during a 1-h exposure to 2-methyl-5-HT (10(-6) M), a 5-HT3 receptor agonist, was significantly increased (317.9 +/- 46.7%, P < 0.05) compared with that of the control tissues (160.4 +/- 8.1%). The 2-methyl-5-HT-induced 5-HT release was significantly inhibited by administration of sendide (10(-6) M) (174.0 +/- 21.6%, P < 0.05) or granisetron (10(-6) M) (186.6 +/- 27.3%, P < 0.05). Since sendide does not penetrate the central nervous system, these results suggest that the antiemetic effects of sendide are due to the inhibition of NK1 and 5-HT3 receptors on the emetic peripheral detector sites.

Animals↗
PubMed1998

Direct evidence of NO production in rat hippocampus and cortex using a new fluorescent indicator: DAF-2 DA.

The biological functions of nitric oxide in the neuronal system remain controversial. Using a novel fluorescence indicator, DAF-2 DA, for direct detection of NO, we examined both acute rat brain slices and organotypic culture of brain slices to ascertain NO production sites. The fluorescence intensity in the CA1 region of the hippocampus was augmented, especially after stimulation with NMDA, in acute brain slices. This NO production in the CA1 region was also confirmed in cultured hippocampus. This is the first direct evidence of NO production in the CA1 region. There were also fluorescent cells in the cerebral cortex after stimulation with NMDA. Imaging techniques using DAF-2 DA should be very useful for the clarification of neuronal NO functions.

Animals↗