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Biomedical subjects

T Furuta

Publications and source records attributed to T Furuta.

At least 181 records · Page 10Linked to original sources

[Distributions of pyrimidine nucleoside phosphorylase (PyNPase) in tissues of benign and malignant mammary diseases--immunohistochemical observations].

Pyrimidine nucleoside phosphorylase (PyNPase) is considered to be important for producing antitumor function of 5'-DFUR or 5-FU inducing compounds, since this enzyme transforms 5'-DFUR into 5-FU and 5-FU into their activated forms. Additionally, PyNPase shows high activity in various malignant tumor tissues. In this investigation, the distributions of PyNPase were examined in the tissues of mastopathy, fibroadenoma, phyllodes tumor and mammary cancer using immunohistochemical procedures. The following results were obtained. In the tissues of mastopathy or fibroadenoma, immunoreactivity was generally very weak and only a few positive epithelial cells were observed. In the phyllodes tumor, immunoreactivity was also weak, but every epithelial cell showed positive immunoreactivity. On the contrary, apparent immunoreactivity was observed in the tissues of mammary cancer, and cancer cells revealed prominent immunoreactivity.

Breast↗

[Usefulness of neoadjuvant brachytherapy in the treatment of pineoblastoma: a case report].

The treatment strategy and prognosis of pineal cell tumors are still subjects of debate because of their rarity and the mixture of pineoblastoma and pineocytoma as components. Pineoblastoma is believed to be the more malignant tumor and total gross resection of this tumor is very difficult because of its invasive tendency and location. Although the effectiveness of external irradiation and chemotherapy has been reported, the outlook for patients with this tumor is extremely poor. We treated a case of pineoblastoma with a single total resection nine months after interstitial irradiation and chemotherapy. In this case, brachytherapy was successful as neoadjuvant therapy for decreasing the tumor's volume and clarifying its boundary. The patient was a 36-year-old woman who had complained of occipital headache for about a month. On admission, neurological examination revealed bilateral papilloedema but, otherwise, there were no deficits. A magnetic resonance image (MRI) showed a homogeneously enhanced tumor in the pineal region and obstructive hydrocephalus. Two weeks after ventriculo-peritoneal shunting, a stereotactic needle biopsy was performed using a BRW MRI-guided stereotactic apparatus, and three catheters for interstitial brachytherapy were implanted into the tumor through the biopsy tract. Iridium-192 seeds were inserted through the catheters and kept there for 8 days to irradiate 40 Gy at the tumor periphery. Four courses of chemotherapy with carboplatin (400 mg/m2) and VP-16 (400 mg/m2) were administered after brachytherapy. Repeat MRI scans every month showed a gradual regression of tumor volume. However, the tumor did not disappear and no further decrease in tumor volume was observed 8 months after brachytherapy. A suboccipital craniotomy was performed 9 months after brachytherapy and en bloc tumor resection was achieved readily via an infratentorial supracerebellar approach. After receiving another course of chemotherapy and external irradiation at 40 Gy, the patient was discharged without any symptoms and no residual tumor or recurrence was observed for 24 months after brachytherapy and 15 months after surgery. The clinical course of this case suggests that a combination of stereotactic biopsy and brachytherapy with chemotherapy followed by surgery may be a good strategy for the treatment of pineal cell tumors regardless of their histopathological features.

Adult↗

Pharmacokinetics of stable isotopically labeled L-histidine in humans and the assessment of in vivo histidine ammonia lyase activities.

The pharmacokinetics of L-histidine in humans has been investigated to evaluate the in vivo histidine ammonia lyase system for the conversion of L-histidine to urocanic acid. Two healthy volunteers (subjects A and B) received a single 100-mg oral dose of L-[3,3-2H2,1',3'-15N2]histidine. Blood and urine samples were obtained over 24 hr after the administration and analyzed by stable isotope dilution ms. Labeled L-histidine was rapidly absorbed, and a maximum plasma concentration of L-histidine was observed at 30 min (1057.6 ng/ml) in subject A and at 60 min (1635.6 ng/ml) in subject B after oral administration. Pharmacokinetic parameters were calculated based on a two-compartment model. Labeled L-histidine in subject A (t1/2 = 1.0 hr) was eliminated approximately twice faster than that in subject B (t1/2 = 1.9 hr). Total body clearances were 70.0 liters/hr in subject A and 30.0 liters/hr in subject B. The low ratios of the renal clearance to the total body clearance (1.04% for subject A and 0.43% for subject B) indicated that most of L-histidine was eliminated via the nonrenal processes. L-Histidine was rapidly metabolized to urocanic acid. Maximum plasma concentrations of urocanic acid were 59.61 ng/ml at 30 min for subject A and 46.10 ng/ml at 60 min for subject B. The slope of the plot of urinary excretion rate of urocanic acid vs. the plasma concentration of unchanged L-histidine was demonstrated to reflect the metabolic clearance of L-histidine to urocanic acid. The method of evaluating the in vivo human histidine ammonia lyase activities discussed in this study offers a significant value with regard to the biochemical and clinical elucidations of the heterogeneity of histidinemia.

Adult↗

Malignant astrocytomas with homozygous CDKN2/p16 gene deletions have higher Ki-67 proliferation indices.

p16 is involved in a cell-cycle regulatory cascade that includes cyclin-dependent kinase 4 (cdk4), cyclin D1 and pRb. Alterations of each of these components have been described in primary human glioblastoma multiforme (GBM) or GBM cell lines, and alterations of the individual components of this pathway appear inversely correlated with one another. While this suggests that disruption of any individual component has similar oncogenic effects, homozygous deletions of the CDKN2/p16 gene are the most common genetic alteration. We investigated the relationship between homozygous CDKN2/ p16 deletions and cellular proliferation in 50 primary astrocytomas (2 WHO grade I pilocytic astrocytoma, 15 grade II astrocytomas, 20 grade III anaplastic astrocytomas and 13 grade IV GBMs). Using a comparative multiplex PCR assay, homozygous deletions of the CDKN2/p16 gene were detected in 5 anaplastic astrocytomas (25%) and 6 GBMs (46%), but in none of the lower-grade tumors. Ki-67 immunohistochemistry was used to assess the number of proliferating cells in the same samples used for molecular genetic analysis. In both anaplastic astrocytomas and GBMs, Ki-67 proliferation indices were significantly higher in tumors with CDKN2/p16 deletions (20%) than in those without deletions (10%; p = 0.0001). These results suggest that homozygous CDKN2/p16 deletions in high-grade astrocytomas may have a more deleterious effect on cell cycle control than the other aberrations in the p16-cdk4-cyclin D1-pRb pathway, and may provide one explanation for why homozygous CDKN2/p16 deletions are more common genetic events in high-grade astrocytomas than RB mutations or CDK4 amplification.

Adult↗

Laparoscopic minilaparotomy pancreaticoduodenectomy with lymphadenectomy using an abdominal wall-lift method.

Because of technical difficulties attributable to the lack of appropriate techniques, the high cost of laparoscopic instruments, and the need for numerous disposable stapling devices, laparoscopic pancreaticoduodenectomy has been performed in only two patients. To solve the above problems, we devised a method of laparoscopic minilaparotomy using an abdominal wall-lift method and have successfully used it to perform pancreaticoduodenectomy with lymphadenectomy in a patient with distal choledochal cancer.

Abdominal Muscles↗

Synthesis of caged compounds of L-leucyl-L-leucine methyl ester, an apoptosis inducer, and their cytotoxic activity.

In this study, we newly synthesized caged compounds of L-leucyl-L-leucine methyl ester and examined their photochemical and immunological properties. From the viewpoints of solubility in phosphate-buffered saline containing 1% dimethyl sulfoxide as well as photoreactivity, we chose two caged compounds, 1 and 2, for study. Upon irradiation, L-leucyl-L-leucine methyl ester with a trans-o-hydroxycinnamoyl group (1) releases L-leucyl-L-leucine methyl ester quite slowly, whereas L-leucyl-L-leucine methyl ester with an o-nitrobenzyl group (2) releases L-leucyl-L-leucine methyl ester quickly. Both irradiated compounds induced apoptosis of U937 cells, as evidenced by a decrease in cell size, although 1 itself caused necrosis (cell swelling) of these cells.

Antineoplastic Agents↗

Relationship between expression of a major apurinic/apyrimidinic endonuclease (APEX nuclease) and susceptibility to genotoxic agents in human glioma cell lines.

The multifunctional DNA repair enzyme (APEX nuclease) having apurinic/apyrimidinic (AP) endonuclease, 3'-5' exonuclease, DNA 3' repair diesterase and DNA 3'-phosphatase activities is thought to be involved in repair of AP sites and single-strand breaks with 3'-blocked termini. To investigate the biological role of the enzyme, we studied the correlation between APEX AP endonuclease activity in several human glioma cell lines having various degree of its expression and cellular susceptibility to cytotoxic agents such as methyl methanesulfonate (MMS), 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3- (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), cis-diamminedichloroplatinum(II) (CDDP), etoposide (VP-16), hydrogen peroxide (H2O2), hyperthermia and X-ray. The cell lines having lower APEX expression showed higher sensitivity to MMS and H2O2 which are known to induce AP sites and single strand breaks on DNA, respectively. The cellular susceptibility to the other agents tested was not significantly correlated to the APEX expression. The present results are thought to support the notion that APEX nuclease plays an important role on repair of AP sites and single-strand DNA breaks with 3'-blocked termini in mammalian cells.

Antineoplastic Agents↗

Laparoscopic minilaparotomy Billroth I gastrectomy with extraperigastric lymphadenectomy for early gastric cancer using an abdominal wall-lifting method.

Laparoscopic gastrectomy with extraperigastric lymphadenectomy for early gastric cancer has never been performed because of technical difficulties attributable to the lack of appropriate techniques, the high cost of laparoscopic instruments, and the need for numerous disposable stapling devices. In order to solve these problems, we have designed a method of laparoscopic minilaparotomy using an abdominal wall-lifting method, and a patient with early gastric cancer (depth of submucosa) underwent by this laparoscopic minilaparotomy distal gastrectomy with extraperigastric lymphadenectomy. During his postoperative recovery, the patient requested no narcotic analgesic, and was discharged on postoperative day 14.

Abdominal Muscles↗

Inflammatory responses in open versus laparoscopic herniorrhaphy.

The aim of this study is to verify whether differences could be found or not as concerns of the postoperative surgical stress between the conventional open herniorrhaphy and laparoscopic herniorrhaphy. We therefore compared the immunological and inflammatory responses to open and laparoscopic procedures in this study. The sex, age, weight, and height characteristics of group 1 (open surgery group) matched those of group 2 (laparoscopic surgery group), and no statistically significant differences were found between them. Nor were there any statistically significant differences in operating time or the postoperative hospitalization. Blood samples were collected preoperatively [postoperative day (POD)0], POD 1 and 5, and the following parameters were assessed: total leukocyte (WBC) count, including neutrophil and lymphocyte subpopulations, HLA-DR+CD3+, IL-6, C-reactive protein (CRP), serum albumin, and body temperature. No differences were detected between two groups in leukocyte, neutrophil, or lymphocyte count, HLA-DR+CD3+, IL-6, albumin, or body temperature or any of the postoperative days. The only statistically significant difference was a higher CRP value in the laparoscopy group than the open group only on POD 1 (p < 0.05). It can be concluded that the laparoscopic approach appears to offer no advantages over the open approach to herniorrhaphy from the standpoint of immunological and inflammatory responses.

Body Temperature↗

Synchronous multicentric development of hepatocellular carcinoma.

Recently, the multicentric origin of hepatocellular carcinoma (HCC) has been recognized, but its clinical importance has still not yet been clarified. The histological characteristics of small hyperechoic HCCs coexisting in 44 consecutively resected Japanese patients whose main HCCs were < 5.0 cm in size were studied. Twelve small hyperechoic HCCs were found and classified into the following two groups: eight nodules in seven patients (15.9%) were early-stage HCC, and four nodules in four patients (9.1%) were more advanced HCC. Thus, early-stage HCC comprised 66.7% of the small echogenic HCCs. Eight HCCs detected as small hyperechoic lesions (found in 15.9% of the patients) showed varying degrees of fatty change yet proved to be well differentiated and retained the preexisting liver structure of either associated liver cirrhosis or chronic hepatitis. Moreover, the histologic characteristics of the eight early-stage HCCs were different from those of the main HCCs. In conclusion, approximately 15% of HCCs in Japanese patients may have a synchronous multicentric origin, and small hyperechoic lesions should be carefully evaluated. However, in the United States or other areas where the occurrence of fatty liver is common, that advice for small hyperechoic lesions may be overly cautious.

Adult↗

Effects of lansoprazole with or without amoxicillin on ulcer healing: relation to eradication of Helicobacter pylori.

We studied the effects of lansoprazole with or without amoxicillin on the quality of ulcer healing in relation to eradication of Helicobacter pylori. Ulcer healing rates for lansoprazole 30 mg q.d. alone (group A) were 100% for duodenal ulcers (DU; n = 20) and 92% for gastric ulcers (GU; n = 15). The healing rates for lansoprazole 30 mg plus amoxicillin 1-2 g q.d. (group B) were 100% for both DU (n = 20) and GU (n = 12). Endoscopic findings after treatment showed that the red scar/white scar ratio in group A was 16/4 for DU and 12/1 for GU. The red scar/white scar ratio in group B was 4/16 for DU and 6/6 for GU. The numbers of H. pylori in gastric mucus did not change throughout the course of treatment in group A but decreased significantly, without H. pylori relapse, in group B. Changes in ammonia concentration in gastric juice, as well as serum gastrin and pepsinogen I and II levels, differed between group A and group B. Concomitant treatment with lansoprazole and high-dose amoxicillin eradicated H. pylori and modified gastric secretory function, resulting in high-quality ulcer healing.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Adenosquamous carcinoma of the gall-bladder with gastric foveolar-type epithelium.

An 80 year old Japanese man had adenosquamous carcinoma of the gall-bladder characterized by an adenocarcinoma (AC) in the gall-bladder lumen and a squamous cell carcinoma (SCC) in the invaded region of the liver. In the AC, the tumor cells consisted of atypical columnar epithelium with pseudostratification, mimicking gastric foveolar epithelium, while atypical signet-ring cells were scattered within the SCC. There was an abrupt transition between the AC and SCC areas. The tumor cells in the AC area were intensely positive for galactose oxidase-Schiff staining, and paradoxical concanavalin A staining revealed these tumor cells to have Class II mucins. Immunohistochemically, the tumor cells in foveolar-type adenocarcinoma were diffusely positive for cathepsin D. Flow cytometrical analysis of DNA content showed the AC area to be diploid and the SCC area to be aneuploid. The S-phase fraction of the SCC area (46.9%) was larger than that of the AC area (19.5%). The positive rate of immunostaining for proliferating cell nuclear antigen in the SCC area (mean 50.627%) was larger than that of the AC area (mean 3.048%, P < 0.01). These results suggest that the AC area of this tumor, histochemically and immunohistochemically, showed gastric foveolar-type characteristics, the SCC component was squamous cell metaplasia of the pre-existing AC, and that the SCC area had a greater proliferating capacity than the AC area.

Aged↗

Multiple endocrine neoplasia type 1 accompanied by duodenal carcinoid tumors and hypergastrinemia: a familial case.

A 38-year-old female was admitted for investigation of the cause of hypergastrinemia, hypercalcemia and an elevated plasma parathyroid hormone (PTH) level. Her siblings, elder brother and sister who had duodenal carcinoid tumor with hypergastrinemia and parathyroid adenomas, were diagnosed as multiple endocrine neoplasia (MEN) type 1. In the present patient, endoscopic examination showed a carcinoid tumor of the duodenum, but examinations by computed tomography (CT) and ultrasonography of the abdomen failed to reveal pancreatic lesions. Serum gastrin levels of this patient and her siblings improved to the normal level after resection of carcinoid tumors. The hypergastrinemia accompanying MEN type 1 in these cases might be due to carcinoid tumor of the duodenum.

Adult↗

Resection of deep-seated gliomas using neuroimaging for stereotactic placement of guidance catheters.

A simple computed tomography- (CT) or magnetic resonance (MR) imaging-guided stereotactic method for guided microsurgical resection of either deep-seated gliomas or tumors adjacent to an eloquent area is described. The technique employs the Brown-Roberts-Wells stereotactic system and twist drills, 2.7 mm in diameter, for the stereotactic placement of 2.4 mm diameter scaled guidance catheters through the calvaria. In a patient with a deep-seated small glioma, less than 2 cm diameter, one catheter was implanted into the center of the enhanced mass through the cerebral cortex. In the other 14 patients, three to six catheters were used which made the tumor border clearer. After implantation of the guidance catheters, the stereotactic frame was removed and a standard open craniotomy performed. Target localization is not affected by brain movement, which is inevitable during open surgery. The tumor involved the frontal lobe in eight patients, the parietal lobe in two, and the thalamus in five. In all cases the lesion was quickly localized and radical removal was achieved. Neurological complications occurred in only one patient who suffered transient hemiparesis after the resection of a lesion in the pyramidal tract. The results demonstrate that microsurgery combined with CT- or MR imaging-guided stereotactic placement of guidance catheters is a new option for surgery of deep-seated gliomas or tumors adjacent to an eloquent area.

Adult↗

192Ir induced radiation damage in monkey brain assessed with magnetic resonance imaging and histological examination.

The effects of irradiation on a large volume of normal brain tissue as occurs in interstitial brachytherapy were investigated. Double iridium-192 seed assemblies were stereotactically implanted into the right centrum semiovale of eight adult Japanese monkeys (Macaca fuscata). The morphological changes induced in the normal brain tissue were evaluated with magnetic resonance (MR) imaging with and without gadolinium-diethylenetriaminepenta-acetic acid (Gd) enhancement at 2 days and 1, 3, and 6 months after the brachytherapy. After each MR imaging examination, randomly selected experimental animals were sacrificed to analyze the histological changes. The low intensity area seen inside the ring of contrast enhancement on the T1-weighted image with Gd enhancement was well correlated with histologically defined necrosis. The high intensity area seen outside the area showing contrast enhancement on the T2-weighted image was well correlated with an area of histological edema and demyelination. The sizes of the lesion and the high intensity area were maximum during the acute stage (2 days) following interstitial irradiation. This monkey model with MR imaging can be used to investigate the development of brain damage induced by interstitial irradiation. We further recommend careful monitoring to detect the development of brain edema during the acute stage after interstitial brachytherapy, especially when large tumors are treated.

Animals↗