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T Furukawa

Publications and source records attributed to T Furukawa.

At least 127 records · Page 7Linked to original sources
PubMed2000

Effect of troglitazone on the liver of a Gunn rat model of genetic enzyme polymorphism.

There is a possibility that serious liver dysfunction rarely observed in diabetic patients given troglitazone is attributable to idiosyncratic abnormalities in liver drug-metabolism. In addition, the results of blood biochemical examinations in serious cases of liver dysfunction showed a tendency for a high level of total bilirubin (T-Bil) over a long period compared with other indicators of liver dysfunction. Thus, we focused on genetic variation of UDP-glucuronosyltransferases (UGTs) that are involved in the conjugation of troglitazone and bilirubin. In this study, Gunn rats, which are hereditarily deficient in the UGT1 family of UGT isozymes, and Wistar rats, the parent strain of Gunn rats, were treated with troglitazone for 3 months at dose levels of 0, 100 or 400 mg/kg to investigate two possibilities: first, whether the genetic deficiency in UGT1s induces an alteration of the metabolic profile of troglitazone followed by liver dysfunction, and second, whether the dosing of troglitazone to Gunn rats which show hyperbilirubinemia result in liver dysfunction. As a result, the metabolic profile of troglitazone in Gunn rats was much the same as that of Wistar rats, suggesting that genetic deficiencies in UGT1s did not influence the metabolic profile of troglitazone. Moreover, no elevation of blood biochemical parameters, such as asparate aminotransferase (AST) and alanine aminotransferase (ALT), or histopathological liver injuries, such as hepatocellular degeneration and necrosis, were observed in either strain of rats, and hyperbilirubinemia in Gunn rats was not aggravated by the dosing of troglitazone. These results strongly suggest that troglitazone was not metabolized by UGT1s but by other UGT isozyme (s) in rats, and that glucuronidation of troglitazone did not compete with glucuronidation of bilirubin in vivo. Thus, it is suggested that high levels of total bilirubin in patients with liver dysfunction induced by troglitazone are attributable to hypofunction due to hepatocellular injury, not to metabolic competition of bilirubin with troglitazone. Moreover, it is also suggested that the deficiency in the UGT1 family of UGT isozymes itself may not be the cause of liver dysfunction associated with troglitazone treatment.

Animals↗
PubMed2000

Importance of sex and age factor in assessing family history of stroke.

Incidence of stroke differs between men and women and it increases nearly exponentially with age. Therefore, assessment of family history of stroke disregarding sex and age of family members results in bias or misclassification. In this study the effects of sex and age on the positivity of the past history were analyzed numerically. Sex- and age-specific proportion of a positive history of stroke among 24,007 family members was obtained from a questionnaire survey of 2,316 high school students. By analyzing the sex- and age-specific proportion with the logistic regression model odds ratios resulting from sex and age difference were estimated. The odds ratio for sex difference was 2.458 (95% confidence interval: 2.067-2.924) and odds ratio for age difference was 1.064 (95% confidence interval: 1.058-1.070). This indicated that a positive history of stroke was 2.458 times higher in male members than in female members of the same age and that a positive history increased by (1.064)y, where y was age difference in years. Potential bias or misclassification resulting from disregarding sex and age can be substantial. Some measures to control for sex and age of family members are required in assessing the family history.

Adolescent↗
PubMed2000

Not hMSH2 but hMLH1 is frequently silenced by hypermethylation in endometrial cancer but rarely silenced in pancreatic cancer with microsatellite instability.

Disruption of the DNA mismatch repair (MMR) system has been found to play an important role in sporadic human cancers of several organs such as colorectum, stomach, endometrium, and pancreas. In cancers of the former three organs, disruption of the MMR system is mainly caused by hypermethylation of the hMLH1 gene. We investigated the expression of the hMLH1 and hMSH2 proteins immunohistochemically in pancreatic and endometrial cancers with high frequency microsatellite instability (MSI-H). Loss of expression of hMLH1 was found in none of seven pancreatic cancer, whereas eight (57%) of 14 endometrial cancer showed loss of expression of hMLH1. On the other hand, one (14%) of seven pancreatic cancers and two (14%) of 14 endometrial cancers showed loss of hMSH2 expression. We further analyzed the methylation status at the promoter region of the hMLH1 and hMSH2 genes and found hypermethylation of hMLH1 at the promoter region in the great majority of endometrial cancers with loss of expression. However, no pancreatic cancer showed hypermethylation. We then further analyzed 22 pancreatic cancer cell lines and obtained similar results. These results suggested that MSI-H in pancreatic cancer is probably caused by different mechanisms from those of other sporadic cancers with MSI-H.

Adaptor Proteins, Signal Transducing↗
PubMed2000

[Concurrent chemoradiotherapy for locally unresectable head and neck cancer].

In patients with locally unresectable head and neck cancer with large nodal involvement, the expected five-year survival is as low as 1-2%. To improve the prognosis of these patients, we studied the usefulness of concurrent chemoradiotherapy in a phase II trial. Between September 1996 and May 1999, thirty-five patients with locally unresectable head and neck cancer were administered concurrent chemoradiotherapy consisting of low-dose and long-term treatment with cisplatin (CDDP) plus 5-fluorouracil (5FU), or (L-CF); the L-CF regimen consisted of CDDP, 3 mg/m2 on 5 days of the week and 5FU, 150 mg/m2 as a 24-hour infusion on 5 days of the week. Concurrently, conventional radiotherapy was given up to total dose of around 60 Gy. In the 33 patients evaluable for response, 17 complete and 9 partial responses were noted, with an overall response rate of 79%. Oral mucostis and myelosuppression were the major side effects and mucositis was a dose limiting toxicity. This study demonstrates increase in survival among the responders (complete + partial) in the concurrent chemoradiotherapy setting. However 8 local relapses were eventually noted in the 17 complete responders. We concluded that this treatment strategy was beneficial in patients with locally unresectable head and neck cancer.

Adult↗
PubMed2000

[Influence of vestibular input on visually guided saccades].

A common pathway in the brainstem is thought to exist for the induction of visually guided saccades and rapid phase nystagmus (Ref. Ohki et al. 1988). This common pathway is often referred to as "the saccade generator" or "the burst generator." The presence of this pathway suggests that vestibular function can be examined by applying "visual stimuli" and "vestibular stimuli" at the same time. We therefore investigated whether caloric stimulation affects the latency, amplitude and velocity of saccadic eye movements and if so, how. Nine normal volunteers participated in the experiment. Eye movements were recorded using DC electrooculography. Caloric stimulation was applied to the right ear using an air caloric stimulator (10 degrees C) during saccades. Two experiments involving visually guided saccades were performed. Task 1: The subject was asked to fixate on a central fixation point. Another spot of light then randomly appeared at one of two different locations (20 degrees to the right or left). The subject was then asked to scan towards the second light as quickly as possible. Task 2: The procedure was the same as in Task 1, except that the target appeared only briefly and then later reappeared at the same location. The saccade latency was unaffected by caloric stimulation in Task 1, while the latency of the rightward saccades increased significantly in Task 2. The saccade amplitude and velocity increased significantly in both directions in Task 1, while the amplitude and velocity of the leftward saccades increased significantly in Task 2. These results can be explained by the synergistic activation of Burster-Driving Neurons by the saccade signal and the vestibular signals. The combinations of these saccade tasks and caloric stimulation, especially Task 2, may be useful in clinically examining vestibulo-oculomotor functions.

Adult↗
PubMed2000

[Surgery using master-slave manipulators and telementoring].

Master-slave manipulators enhance surgeons' dexterity and improve the precision of surgical techniques by filtering out surgeons' tremors and scaling the movements of surgical instruments. Among clinically available master-slave manipulators, the epoch-making system called "da Vinci" developed by Intuitive Surgical Inc. (Mountain View, CA, USA), equipped with 2 articulated joints at the tip of the surgical instruments allowing 7 degrees of freedom, mimics the movements of surgeons' wrists and fingers in the abdominal or thoracic cavity. Today advanced telecommunications technology provides us excellent motion images using only 3-ISDN telephone lines. Experienced surgeons at primary surgical sites have been able to perform complex procedures successfully by consulting specialists at remote sites. Because telecommunications costs have become lower each year, telementoring will be come a routine surgical practice in the near future. The usefulness of surgical telementoring has been greatly enhanced by the development of a technique to illustrate on video images from two directions. Moreover, remote advisory surgeons will be able to provide the optimal operative field to operating surgeons using robotic camera holders with voice-recognition systems. In the near future, when master-slave manipulators will also be coupled with telementoring systems, remote experts could actually perform complex surgical procedures.

Humans↗
PubMed2000

[The validity of the sentinel node concept in gastrointestinal cancers].

Although the sentinel node concept has been validated and clinically applied to breast cancer and malignant melanoma, its clinical significance in other solid tumors has not been thoroughly investigated. With regard to gastrointestinal (GI) cancers in particular, our surgeons have been cautious because of the high frequency of skip metastasis and the complicated lymphatic system in the GI tract. We would like to emphasize that so-called skip metastasis has been defined according to anatomic classification of regional lymph nodes and that the lymphatic drainage route must be patient or lesion specific. To test the validity and feasibility of this concept in GI cancers, we have established a radio-guided intraoperative sentinel node navigation system using preoperative endoscopic submucosal injection of radioactive tracer followed by intra-operative gamma-probing. In 131 patients with GI cancers (esophagus: 22, stomach: 71, colorectum: 38), the detection rate of sentinel nades was 91% and overall diagnostic accuracy of lymph node metastasis by sentinel node status was 97%. Initial results suggest further investigation of this procedure as an accurate staging and a minimally invasive approach to early GI cancers.

Gastrointestinal Neoplasms↗
PubMed2000

[A case of angiosarcoma in retroperitoneal cavity].

We report a case of angiosarcoma in the retroperitoneal cavity. A 66-year-old man was admitted to our hospital with the complaint of chest discomfort. Imaging studies including computed tomography scan and magnetic resonance imaging revealed a large solid retroperitoneal mass adjacent to the bladder. There was no evidence of metastasis. The tumor was surgically resected and histopathologically diagnosed as angiosarcoma from the positive staining for VIIIth factor, mitotic figures and abnormal endothelial cells. Six months after surgery, local recurrence adjacent to the bladder appeared. We resected the mass and started adjuvant therapy using Interleukin-2. However, he died of progressed disease one year after the first operation.

Aged↗
PubMed2000

[Histoculture drug response assay on non-small cell lung cancer].

We examined the chemosensitivity of non-small cell lung cancer (NSCLC) tissues to CDDP, 5-FU, ADM, MMC, ETP and SN38 using histoculture drug response assay (HDRA). One-hundred and thirty surgical specimens from NSCLC patients who were not given preoperative chemotherapy were used. The inhibition indexes of CDDP, 5-FU, MMC, ADM, ETP and SN38 were 39.1 +/- 18.2%, 48.0 +/- 19.7%, 63.3 +/- 17.7%, 47.6 +/- 22.0%, 36.9 +/- 21.1%, and 37.9 +/- 25.2%, respectively. Inhibition indexes were above the cutoff level, i.e., 'judged sensitive,' in 40 cases (31.3%) for CDDP, 34 cases (27.4%) for 5-FU, 54 cases (44.3%) for MMC, 36 cases (33.0%) for ADM, 29 cases (29.8%) for ETP, and 34 cases (37.4%) for SN38, respectively. In almost one-third of patients, the inhibition indexes of all drugs were under cutoff levels. Correlations between in vitro chemosensitivity data and patient responses to chemotherapy were obtained from 16 evaluable patients, and a 44.4% true positive rate and a 100% true negative rate were observed. Our results with HDRA for NSCLC showed a high incidence of intrinsic multidrug resistance. HDRA may help doctors to avoid non-effective chemotherapy for NSCLC patients.

Adenocarcinoma↗
PubMed2000

Scarless endoscopic thyroidectomy: breast approach for better cosmesis.

An original technique for performing endoscopic thyroidectomy using a breast approach to avoid an operative scar in the neck was developed. The subcutaneous space in the breast area and the subplatysmal space in the neck were bluntly dissected through a 15-mm incision between the nipples, and CO2 was insufflated at 6 mm Hg to create the operative space. Three trocars were inserted at the breast, and dissection of the thyroid and division of the thyroid vessels and parenchyma were performed endoscopically using an ultrasonically activated scalpel. Four hemithyroidectomies and one partial resection of the thyroid for five female patients with thyroid adenomas 5 to 7 cm in diameter were successfully performed using this procedure. There were no conversions to open surgery or complications. No scars were apparent in the neck, and all patients were fully satisfied with the cosmetic results. Endoscopic thyroidectomy using a breast approach and low-pressure subcutaneous CO2 insufflation is a feasible and safe procedure, which results in satisfactory cosmetic results.

Adenoma↗
PubMed2000

[Sensitivity of UCN-01 lies in the balance of CDK 2 kinase and p21].

Five human cancer cell lines (MKN 45, HT-29, WiDr, PAN-3-JCK, and CRL 1420) were used to evaluate the antitumor spectrum of UCN-01, which suppressed the growth of these digestive cancer cell lines. A human pancreatic cancer xenograft (CRL 1420) and breast cancer xenograft (MX-1) were used to determine their sensitivity to UCN-01, in nude mice. UCN-01 significantly suppressed the tumor growth of CRL 1420 at a dose of 10 mg/kg in a schedule of (qd x 5) x 2, but was ineffective for MX-1. While p21 protein expression was induced by UCN-01 in both CRL 1420 and MX-1, an accumulation of dephosphorylated ppRb was observed only in CRL 1420, resulting in G1 block as detected by flow cytometric analysis. The CDK 2 activity of MX-1 was almost 6 times higher than that of CRL 1420, which might account for the resistance of MX-1 to UCN-01 in spite of the induction of p21 in this strain. We conclude that the determinant of sensitivity to UCN-01 lies in the balance of CDK 2 kinase activity and p21 protein induction.

Alkaloids↗
PubMed2000

[Curative laparoscopic surgery for early gastric cancer: eight years experience].

We have applied two different laparoscopic surgical techniques for early gastric cancer and have successfully treated 111 patients since March 1992. The indications are: 1) preoperative diagnosis of mucosal cancer; 2) lesion size of < 25 mm if the protruding type; and 3) lesion size < 15 mm and UI (-) if the depressed type. The first technique is laparoscopic wedge resection of the stomach using a lesion-lifting method (n = 93). The gastric wall around the cancerous lesion is exposed laparoscopically. The abdominal wall and gastric wall in the vicinity of the lesion are pierced using a 12-G sheathed needle. A small metal rod with a fine wire is introduced into the stomach through the outer sheath. By retracting the metal rod, the lesion can be lifted precisely (i.e., lesion-lifting method). Wedge resection at a sufficient distance from the metal rod is carried out using an endoscopic stapler. The second technique is referred to as laparoscopic intragastric mucosal resection (n = 18). Three balloon trocars are placed in the stomach laparoscopically. The stomach is then insufflated with CO2, and surgical instruments are introduced. The mucosal and submucosal layers around the lesion are resected with sufficient surgical margins. The selection of the laparoscopic technique depends on the site of the cancerous lesion. In our series of 111 patients, sufficient horizontal (mean 15 +/- 5 mm and 8 +/- 4 mm, respectively, using the first and second technique) and vertical surgical margins were achieved. There was no mortality and no major complications in patients undergoing either surgical technique. There have been two recurrences, both mucosal lesions found 2 years after the initial surgery, which were successfully treated with gastrectomy and laser irradiation. All patients have survived for 3 to 96 months, and there has been no trocar site recurrence. In conclusion, these laparoscopic procedures are curative and minimally invasive treatments for early gastric cancer.

Gastric Mucosa↗
PubMed2000

Inhibition of ATRA-induced myeloid differentiation in acute promyelocytic leukemia by a new protein tyrosine phosphatase inhibitor, 3,4-dephostatin.

We previously reported that the expression and the activity of SHP-1, a non-transmembrane protein tyrosine phosphatase (PTPase) increased during myeloid differentiation of an acute promyelocytic leukemia cell line (HT93) induced by all-trans retinoic acid (ATRA). To examine whether inhibition of SHP-1 activity attenuates myeloid differentiation, we used a new PTPase inhibitor, 3,4-dephostatin, and studied its effect on myeloid differentiation. Suppressive effects on immunoprecipitated SHP-1 phosphatase activity and myeloid cell differentiation were detected. These results suggest that SHP-1 is a substrate for 3,4-dephostatin, and that SHP-1 PTPase activity is closely related to myeloid differentiation.

Cell Differentiation↗
PubMed1999

Effects of nitric oxide, light adaptation and APB on spectral characteristics of H1 horizontal cells in carp retina.

The spectral characteristics of cone-driven horizontal cells of H1 subtype (H1 HCs) receiving main synaptic input from red-sensitive cones were studied in light- and dark-adapted retinae of carp. The spectral sensitivity profile of H1 HCs in dark-adapted retinae was practically the same as the absorption spectrum of red-sensitive cones. Light-adaptation decreased the sensitivity preferentially in the short-wavelength (blue/green) region, resulting in a relative enhancement of the 617 nm peak. Application of nitric oxide (NO) donors, sodium nitroprusside (SNP) and S-nitrosoglutathione (SNOG or GSNO), or dopamine to dark-adapted retinae decreased the sensitivity preferentially in blue/green region, an effect similar to that of light-adaptation. Application of haemoglobin (Hb, an NO scavenger) or 2-amino-4-phosphonobutyrate (APB, a metabotropic glutamate receptor agonist), to light-adapted retinae increased the sensitivity preferentially in the blue/green region, an effect similar to dark-adaptation. The photoresponses of H1 HCs were univariant in dark-adapted retinae as well as Hb-treated light-adapted retinae. In light-adapted retinae with normal Ringer, however, the univariance did not hold. These results suggested that the photoresponses of H1 HCs to short-wavelength stimuli contain a depolarising (sign-reversing) component, which can be activated by light-adaptation or application of NO and dopamine, and inactivated by dark-adaptation or deprivation of NO or application of APB.

Adaptation, Ocular↗
PubMed1999

Sex difference in the daily rhythm of hepatic P450 monooxygenase activities in rats is regulated by growth hormone release.

Daily fluctuations have been observed in the hepatic cytochrome P450 monooxygenase activities of rodents. It was confirmed in our previous study that the P450 activities assessed by measurement of 7-alkoxycoumarin O-dealkylase (ACD) showed obvious daily fluctuations in male rats with high values during the dark period. However, there is still very little information about the daily fluctuation of P450 activities in female rats. In the first experiment of the present study, the daily fluctuation of ACD activities in female rats was examined. The results indicated the absence of any apparent daily fluctuation in the hepatic ACD activities of the females, so the study confirmed a sex difference in the daily rhythm of the ACD activities. In the second experiment using hypophysectomized (Hpx) rats, it was investigated whether this sex difference in daily rhythm was attributable to growth hormone (GH) release, an activity which is known to affect the sex difference in the expression of P450 isoforms. It was found that the Hpx rats, given subcutaneous injections of GH twice during the light period to mimic a male pattern of GH secretion, showed obvious light-dark fluctuation in ACD activities with high values in the dark period, and similar results were obtained in sham-operated males. Conversely, the Hpx rats given continuous infusion of GH to mimic a female pattern of GH secretion did not show the light-dark fluctuation in ACD activities, and similar results were obtained in sham-operated females. In conclusion, there is a sex difference in the daily rhythm of the hepatic P450 activities in rats and this difference is apparently influenced by the difference in the patterns of GH secretions.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1999

Osa associates with the Brahma chromatin remodeling complex and promotes the activation of some target genes.

The yeast SWI/SNF complex and its Drosophila and mammalian homologs are thought to control gene expression by altering chromatin structure, but the mechanism and specificity of this process are not fully understood. The Drosophila osa gene, like yeast SWI1, encodes an AT-rich interaction (ARID) domain protein. We present genetic and biochemical evidence that Osa is a component of the Brahma complex, the Drosophila homolog of SWI/SNF. The ARID domain of Osa binds DNA without sequence specificity in vitro, but it is sufficient to direct transcriptional regulatory domains to specific target genes in vivo. Endogenous Osa appears to promote the activation of some of these genes. We show evidence that some Brahma-containing complexes do not contain Osa and that Osa is not required to localize Brahma to chromatin. These data suggest that Osa modulates the function of the Brahma complex.

Animals↗
PubMed1999

Bonding behavior of ultrahigh strength unsintered hydroxyapatite particles/poly(L-lactide) composites to surface of tibial cortex in rabbits.

Unsintered hydroxyapatite particles/poly(L-lactide) (u-HA/PLLA) composites with an initial bending strength of up to 270 MPa were developed based on the hypothesis that inclusion of u-HA particles in a PLLA matrix might enhance bone bonding. The purpose of this study was to examine the bonding strength and behavior of these u-HA/PLLA composites on the surface of the bone cortex. Composites containing 30 (u-HA30), 40 (u-HA40), or 50 wt % (u-HA50) of fine u-HA particles (3-microm average particle size) were prepared. Semicolumnar plates of these composites and control PLLA plates were fixed with metal screws to the surface of both proximal tibial cortices in 45 rabbits. The loads required to detach the plates from the bone cortex surface, defined as the bonding strengths, were measured at 4, 8, and 25 weeks after implantation. Bonding strengths in the u-HA30 group at 8 weeks and in the u-HA40 and u-HA50 groups at each postimplantation time were significantly greater than in the PLLA group (post hoc test using Fisher's protected least significant difference method). At each postimplantation time histological examinations revealed direct contact between the bone and the u-HA/PLLA composite plates without any intervening fibrous tissue. There was no evidence of any inflammatory or foreign-body response in any group throughout the follow-up periods. The results of this study suggest that the biodegradable PLLA fixation plates amended with u-HA particles could be functionally superior to PLLA plates without particles.

Animals↗