Biomedical subjects

T Hirota

Publications and source records attributed to T Hirota.

At least 91 records · Page 5Linked to original sources

PubMed1997

Chewing-gum flavor affects measures of global complexity of multichannel EEG.

Global complexity of spontaneous brain electric activity was studied before and after chewing gum without flavor and with 2 different flavors. One-minute, 19-channel, eyes-closed electroencephalograms (EEG) were recorded from 20 healthy males before and after using 3 types of chewing gum: regular gum containing sugar and aromatic additives, gum containing 200 mg theanine (a constituent of Japanese green tea), and gum base (no sugar, no aromatic additives); each was chewed for 5 min in randomized sequence. Brain electric activity was assessed through Global Omega (Omega)-Complexity and Global Dimensional Complexity (GDC), quantitative measures of complexity of the trajectory of EEG map series in state space; their differences from pre-chewing data were compared across gum-chewing conditions. Friedman Anova (p < 0.043) showed that effects on Omega-Complexity differed significantly between conditions and differences were maximal between gum base and theanine gum. No differences were found using GDC. Global Omega-Complexity appears to be a sensitive measure for subtle, central effects of chewing gum with and without flavor.

Adult↗

PubMed1997

Magnetic resonance imaging of rat head with a high-strength (4.7 T) magnetic field.

This study was designed to seek the appropriate scanning parameters for T1 and T2 weighted images of rat head by use of a high (4.7 T) magnetic field strength magnetic resonance imaging unit. The optimum values of variables for T1 weighted images were considered to be a time of repetition of 1,000 msec, and for T2 weighted images, 8 echoes. When the sagittal images of a healthy rat head were scanned using these optimum values, the cerebrum, cerebellum, olfactory bulb, pituitary gland, pineal gland, spinal cord, tongue, nasopharynx, nasal conchae, vermis and cerebrospinal fluid were clearly observed in either T1 or T2 weighted images. Moreover, a primary brain tumor induced by ethylnitrosourea was depicted as a high signal intensity mass in T2 and contrast-enhanced T1 weighted images.

Animals↗

PubMed1997

Pharmacokinetics of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate. 1st communication: absorption, distribution and excretion after single administration of 14C-labeled compound to rats and dogs.

The absorption, distribution and excretion of radioactivity were studied in rats and dogs after intravenous or oral administration of NS-21 ((+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, CAS 129927-33-4). 14C-NS-21 was rapidly absorbed from the gastrointestinal tract after oral administration to rats and dogs. NS-21 was absorbed throughout the whole area of the small intestine. NS-21 entered the systemic circulation via the portal vein because the transfer of radioactivity into the lymph was negligible. The presence of food did not affect the absorption ratio of NS-21. There was no difference in the plasma concentrations of radioactivity after intravenous and oral administrations of 14C-NS-21 to male and female rats. After oral administration of 3, 30 or 100 mg/kg of 14C-NS-21 to rats, the area under the plasma concentration-time curve increased in a dose-dependent manner. After oral administration of 14C-NS-21 to rats, radioactivity was distributed throughout the whole body. The concentrations of radioactivity in most tissues reached their maximums within 2 h, and then declined as the plasma concentration decreased. No radioactivity was detected in most tissues 168 h after administration. In vitro serum binding of 14C-NS-21 was more than 98% in all the animal species tested. NS-21 bound to both human serum albumin and alpha 1-acid glycoprotein. Radioactivity was mainly excreted into the feces via bile in rats, and evenly excreted into the urine and feces in dogs. No differences were observed in the excretion of radioactivity between male and female rats.

Administration, Oral↗

PubMed1997

Pharmacokinetics of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate. 2nd communication: tissue levels and enzyme activity in rats after repeated administration, and placental and milk transfer after single administration.

The absorption, distribution and excretion of radioactivity in rats were studied during and after repeated oral administration of 30 mg/kg of NS-21 ((+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, CAS 129927-33-4) once a day for 21 days. The plasma concentrations of radioactivity 24 h after each administration of 14C-NS-21 reached a steady state on the 5th day. 48 h after the 21st administration, the plasma concentrations of radioactivity were under the detection limit. The plasma concentrations of the radioactivity after the 7th oral administration of 14C-NS-21 was higher than that after the single administration, but similar to those after the 14th and 21st administrations. There were no marked differences in the elimination half-lives after each administration. The urinary and fecal excretion of the radioactivity was 21.5 and 81.3%, respectively, within 168 h after the 21st administration. In most tissues, no radioactivity was observed 336 h after the 21st administration. Repeated oral administration of 30 and 100 mg/kg of NS-21 once a day for 7 days had no effect on the cytochrome P-450 content, aniline hydroxylase and aminopyrine N-demethylase activity in rat liver. The transfer of radioactivity into fetuses and milk was investigated after single oral administration of 14C-NS-21 to female rats. In the 18th day pregnant rats, the radioactivity concentrations were lower in most fetal tissues than in the maternal plasma. After oral administration of 14C-NS-21 to lactating rats, the concentrations of radioactivity were higher in the milk than in the maternal plasma during an 8-h period. No radioactivity was observed in milk 48 h after administration.

Animals↗

PubMed1997

Pharmacokinetics of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate. 3rd communication: plasma concentrations of the unchanged drug and its deethylated metabolite in rats, dogs and monkeys.

1. The plasma concentrations of NS-21 ((+/-)-4-diehtylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, CAS 129927-33-4) and its deethylated metabolite (RCC-36) after intravenous and oral administrations of (S/R)-NS-21 were measured in rats, dogs and monkeys. After intravenous administration, the plasma concentrations of NS-21 decreased biexponentially. The half-lives of NS-21 in the elimination phase were 2.2 h in rats, 5.3 h in dogs and 15.4 h in monkeys. After oral administration, the systemic availabilities were 4% in rats, 22% in dogs and 6% in monkeys. After intravenous administration, the plasma concentrations of RCC-36 were much lower than those of the unchanged drug in all the animal species tested. In contrast, after oral administration, the plasma concentrations of RCC-36 were comparable to those of the unchanged drug in rats and dogs, and were higher in monkeys. This result suggests that RCC-36 is mainly produced by the first-pass effect. 2. The plasma concentrations of NS-21 and RCC-36 after intravenous and oral administrations of (S)- or (R)-NS-21 were measured in dogs. The AUC value of the unchanged drug after intravenous administration of (R)-NS-21 was about twice as large as that of (S)-NS-21. After oral administration, the systemic availabilities of (S)- and (R)-NS-21 were 17 and 22%, respectively. There were no differences in the serum binding between (S)- and (R)-NS-21 in any of the animal species tested including humans. (S)- and (R)-NS-21 were mainly converted to RCC-36 and a 4-cyclohydroxylated metabolite (NS-21-4-OH) in hepatic microsomes of rats, dogs and monkeys. There were no marked differences in the N-deethylation of (S)- and (R)-NS-21 in all the animals. In contrast, (S)-NS-21 was converted to NS-21-4-OH more preferentially than (R)-NS-21 only in dogs. These findings indicate that the stereo-selective disposition of NS-21 in dogs is due to the stereo-selective cyclohydroxylation of NS-21.

Administration, Oral↗

PubMed1997

Pharmacokinetics of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate. 4th communication: metabolism in rats and dogs.

1. The metabolism of NS-21 ((+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, CAS 129927-33-4) was investigated in rats and dogs. Only a trace amount of the unchanged drug was excreted into urine and bile. This result indicates that NS-21 is extensively metabolized. 2. Seven metabolites (M-1 to M-7) were isolated from rat urine after oral administration of NS-21. Their chemical structures were confirmed by mass spectrometry and co-chromatography with the authentic compounds. On the basis of these results, we postulate that NS-21 is metabolized through the following 3 pathways; 1) N-deethylation, 2) hydroxylation of the cyclohexyl ring, and 3)hydrolysis of the ester bond. 3. The concentrations of NS-21 and its metabolites in the plasma, liver, kidney and lung were determined after single and repeated oral administrations of 14C-NS-21. The concentrations of the unchanged drug and its N-deethylated metabolite (RCC-36) in the tissues were higher than those in the plasma 1 h after single administration. There were no differences in the tissue concentrations of the unchanged drug between single and repeated administration except in the liver. 4. After oral administration of 14C-NS-21 to urinary-ducts cannulated rats, the concentrations of the unchanged drug and RCC-36 in the bladder, the target organ, were higher than in the plasma.

Animals↗

PubMed1997

[Treatment results in childhood acute myeloblastic leukemia--a report of clinical trials of a past decade from the Japanese children's Cancer and Leukemia Study Group (CCLSG)].

Treatment results were evaluated in 167 children with acute myeloblastic leukemia (AML) treated on four protocols (ANLL 861, 8912, 9205, APL-ATRA) of the Children's Cancer Leukemia Study Group. In the ANLL 9205 protocol, anthracycline was used with a continuous infusion of cytosine arabinoside, followed by an intensive sequential post remission chemotherapy of short duration, 42/46 patients (91.3%) achieved complete remission, and 58.8% of these patients projected a 3-year disease free survival. These results were apparently superior to those obtained with the ANLL 861 & 8912 protocols, which used conventional doses of multi drugs followed by a moderate post remission chemotherapy of long duration. This favorable response with the ANLL 9205 protocol was attributed mainly to the high induction rate of patients with the M4 and M5 FAB subtypes, as compared to those in the previous two protocols (91.3% in ANLL 9205 vs 57.9% in ANLL 861 + 8912; p < 0.05). No significant difference in the patients outcome was found between the chemotherapy group and allogenic bone marrow transplantation group in the ANLL 9205 study. The patients with the M3 FAB subtype treated with the APL-ATRA protocol which consisted of an alternative use of all-trans retinoic acid and chemotherapy significantly prolonged event free survival as compared with the patients treated with ANLL 861/8912 protocols without all-trans retinoic acid.

Anthracyclines↗

PubMed1997

[Cytogenetic abnormality and prognosis in childhood acute myeloblastic leukemia. Children's Cancer and Leukemia Study Group (CCLSG)].

We report on the leukemic cell karyotype of 180 children with acute myeloblastic leukemia (AML). They were treated by the protocols of chemotherapy for the Children's Cancer and Leukemia Study Group (CCLSG) in the last decade. Of 132 cases with adequate banding analysis, 24.2% had normal karyotype, 21.2% had miscellaneous clonal abnormalities and 54.6% were classified into known cytogenetic subgroups: t(8;21) (n = 35), t(15;17) (n = 23), inv (16) (n = 6), t(11q23;V) (n = 6), -7/7q-(n = 2). Each karyotype was closely correlated with a particular FAB subtype such as t(8;21) in M2, t(15;17) in M3, inv (16) in M4, t(11q23;V) in M5. In the M1+M2 group, although patients with t(8;21) had favorable clinical features such as low WBC counts and less frequent lymphadenopathy, their treatment outcome was not significantly better than those of patients with a normal karyotype (3-year EFS: 58 +/- 11% vs. 47 +/- 12%). Patients with miscellaneous chromosomal abnormalities had a significantly shorter EFS (22% +/- 10%) (p < 0.05) than those with t(8;21) or normal karyotype. In M4+M5 group, 2-year EFS of patients with inv (16) (40 + 30%) was longer than that of patients with normal karyotype (25 +/- 19%), and t(11q23;V) or miscellaneous chromosomal abnormalities (0 +/- 25%). These results suggest that cytogenetic data may be useful for risk-based treatment assignments for children with AML.

Adolescent↗

PubMed1997

[Pharmacokinetic studies of all-trans retinoic acid (ATRA) and pilot study of intermittent schedule of ATRA and chemotherapy in childhood acute promyelocytic leukemia. Children's Cancer and Leukemia Study Group].

A pharmacokinetic study of all-trans retinoic acid (ATRA) was performed in 8 patients with various types of leukemia and MDS. After oral administration at a dose of 30 mg/m2, the mean peak plasma concentration was 430 ng/ml and was reached at 150 min. In one patient who failed to respond a very low plasma ATRA level was seen. Though the plasma ATRA exposure decreased significantly with daily drug administration, an intermittent schedule of ATRA administration would yield higher plasma drug concentrations. We treated 2 patients with refractory acute promyelocytic leukemia (APL) in a pilot study of ATRA followed by intensive chemotherapy (APL-ATRA protocol). Two patients successfully achieved complete remission with ATRA after failing under conventional chemotherapy. Based on the pharmacokinetic study of ATRA, an intermittent schedule of ATRA in addition to chemotherapy suggests an effective regimen for children with APL. Phase II trials to evaluate the role of intermittent schedules of ATRA are planned in Children's Cancer and Leukemia Study Group.

Administration, Oral↗

PubMed1997

[Treatment results of intermittent and cyclic regimen with ATRA and chemotherapy in childhood acute promyelocytic leukemia. Children's Cancer and Leukemia Study Group].

An intermittent and cyclic regimen with All-Trans Retinoic Acid (ATRA) and intensive chemotherapy was conducted due to pharmacokinetic studies on ATRA for acute promyelocytic leukemia (APL) in children. We have treated 17 children with APL using ATRA for remission induction followed by an intermittent schedule of ATRA plus intensive chemotherapy (APL-ATRA protocol). There were 10 males and 7 females. The median age was 9.0 years old. The median baseline white blood cell count was 12.1 x 10(3)/microliter, hemoglobin 7.8 g/dl, platelet 4.5 x 10(4) microliters at diagnosis. Sixteen patients showed t(15; 17) translocation. RT-PCR analysis was available in 15 patients and showed PML/RAR alpha rearrangement in all patients. Overall, 13 or 17 newly diagnosed patients (88%) achieved complete remission and EFS was 67%. Compared to the control (same chemotherapy without ATRA regimen), remission induction and EFS were significantly increased. The toxicity of ATRA consisted of retinoic acid syndrome in 1 and pseudotumor cerebli in another. Other toxicities included headache, chelitis, gastrointestinal trouble and bone pain. These results suggest that intermittent and cyclic regimen with ATRA and intensive chemotherapy (APL-ATRA protocol) is highly effective for APL patients.

Aclarubicin↗

PubMed1996

Primary malignant melanoma (clear cell sarcoma) of bone: report of a case arising in the ulna.

BACKGROUND: To the authors' knowledge, there has been no previous report of primary malignant melanoma of bone. METHODS: A 33-year-old woman presented with a tumorous lesion in the olecranon of the right ulna. The histologic diagnosis was malignant melanoma with close similarity to clear cell sarcoma. To exclude the possibility of malignant melanoma metastatic to the bone, clinical investigations including gallium 67-citrate scintigraphy, brain, chest, and abdominal computed tomography, and upper and lower gastrointestinal endoscopic examinations were performed. Conventional histopathologic, immunohistochemical, and electron microscopic studies were also performed. RESULTS: Clinical investigations showed no lesion suggestive of a primary melanoma other than that in the right ulna. Histologically, the tumor was comprised of polygonal or fusiform cells with clear or granular cytoplasm and vesicular nuclei containing one or two prominent nucleoli. The features were similar to those of clear cell sarcoma (malignant melanoma of soft parts). Fontana preparations and immunohistochemical staining for S-100 protein and HMB-45 (melanoma specific antigen) also revealed that the tumor cells had the characteristics of malignant melanoma. The patient has remained alive and well for more than 5 years after the initial treatment. CONCLUSIONS: The clinicopathologic findings in this case strongly suggested that the lesion was a primary malignant melanoma of bone. Therefore, this is the first report to indicate that malignant melanoma and related diseases can occur even in bone tissue.

Adult↗

PubMed1996

Analysis of PIG-A gene in a patient who developed reciprocal translocation of chromosome 12 and paroxysmal nocturnal hemoglobinuria during follow-up of aplastic anemia.

The relationships between paroxysmal nocturnal hemoglobinuria (PNH), aplastic anemia (AA), and myelodysplastic syndrome (MDS) are not clear. Here we describe a patient, J20, who developed a reciprocal translocation of chromosome 12 and PNH during follow-up of AA. All metaphases in CD59-deficient bone marrow mononuclear cells had the translocation, whereas none of the CD59-deficient cells had it, indicating that the PNH clone coincided with a cell population bearing the chromosomal aberration. We found a somatic single-base deletion mutation in the PIG-A gene of this patient's peripheral blood cells. This is the first patient with PNH with a PNH clone containing a chromosomal translocation.

Adult↗

PubMed1996

Percentage of reversibly and irreversibly sickled cells are altered by the method of blood drawing and storage conditions.

We previously reported that the percentage of reversibly and irreversibly sickled cells (RSC and ISC, respectively) in the blood of patients with sickle cell disease is strongly influenced by the method of blood drawing (PNAS 91:12589, 1994). We now document the effect of blood storage conditions on the percentage of RSC and ISC. The percentage of RSC was lowest when blood was stored at 0 degree C, while the percentage of RSC was highest in specimens kept at 37 degrees C. At room temperature, the percentage of RSC increased slightly over 8 hours. The percentage of ISC was also temperature dependent and was reduced significantly upon cooling. Our results showed that many ISC reverted to a discoidal shape after 3 hrs of cooling after treatment of blood with oxygen or carbon monoxide. Since no Hb S polymers were detected in ISC treated with oxygen or carbon monoxide, the time required for shape restoration may be attributed to the membrane. We measured ISC levels of 10 patients with consideration of storage temperature and compared the values with those determined by the conventional method and also with those published previously.

Anemia, Sickle Cell↗

PubMed1996

Bacteria closely resembling Helicobacter pylori detected immunohistologically and genetically in resected gallbladder mucosa.

A microorganism with close immunohistological and genetic resemblance to Helicobacter pylori was found in the resected gallbladder mucosa of a 41-year-old woman. The woman was admitted to hospital complaining of fever and right hypochondrial pain. Cholecystectomy was carried out under the diagnosis of gallstones and cholecystitis. A microorganism resembling H. pylori (stained with H&E, Giemsa, and Wartin-Starry) was detected incidentally on pathological examination. The microorganism was also positive for immunohistochemical staining. An amplification reaction was seen on genetic examination by the polymerase chain reaction (PCR) method (urease beta-genes). Our findings suggest that H. pylori may be present in tissues other than gastric mucosa.

Adult↗

PubMed1996

Solitary pancreatic metastasis occurring eight years after nephrectomy for renal cell carcinoma. A case report and surgical review.

CONCLUSION: Pancreatic metastasis from renal cell carcinoma is extremely rare. The average time between nephrectomy and the diagnosis of metachronous metastases is reported to exceed 10 yr. Therefore, the initial diagnosis may be neglected in the cases of prolonged disease-free interval. When it does occur simultaneously or metachronously, aggressive surgical resection, when possible, seems to be the most effective treatment for this metastatic lesion. BACKGROUND: An 81-yr-old female patient, who 8 yr previously had undergone right radical nephrectomy for renal cell carcinoma, presented with solitary pancreatic metastasis, which was successfully treated with a distal pancreatectomy. Only 66 cases of clinically diagnosed renal cell carcinoma metastatic to the pancreas are reported in the world literature and 49 of the patients (including ours) underwent a definitive surgical resection. Our case, treated by distal pancreatectomy, and a review of the relevant literature including all reported cases of renal cell carcinoma metastatic to the pancreas, are presented. RESULTS: The patient was well without any evidence of recurrence at 22 mo after the operation.

Aged↗

PubMed1996

Image quantitation of intestinal metaplasia in entire gastrectomy specimens from Swedish and Japanese patients.

The aim of this work was to investigate the extension of intestinal metaplasia (IM), as well as to quantitate various components of IM (namely sialomucins, sulfomucins and Paneth cells), in entire gastrectomy specimens from Swedish and Japanese patients. The length of the gastric mucosa was assessed by morphometry. The percent of sections with IM was regarded as the extension of IM in the specimens. Histochemically labeled sialomucins, sulfomucins and Paneth cells (the 3 main findings in gastric IM) were quantified in separate sections with the aid of an image analyzer. In total, 1,321 sections corresponding to 6 gastrectomy specimens were quantified. Sialomucins and sulfomucins were more extensively distributed in the 4 specimens with carcinoma than in the 2 without carcinoma (one having a peptic ulcer and the other, hereditary gastric cancer syndrome (HGCS) without carcinoma). On the other hand, quantitative analysis in Swedish specimens indicated that the highest values for sialomucins, sulfomucins and Paneth cells were present in HGCS. When Swedish and Japanese specimens with adenocarcinoma were compared, only sulfomucins (denoting Types II and III IM) were significantly higher in those carrying an intestinal-type carcinoma (ITC) than in those with diffuse-type carcinoma (DTC). The results substantiate those obtained with gastric biopsies by other authors. On the other hand, the mucosal extension and the amount of sulfomucins are not comparable parameters (since that mucin was not equally distributed, but "concentrated" in certain areas in the mucosa). One possible conclusion is that the focal distribution of acidic mucins and of Paneth cells in the gastric mucosa may strongly influence their detection rate in gastric biopsies. Thus, haphazard biopsy of the gastric mucosa may fail to sample areas with sulfomucins in population studies aiming to detect individuals at risk. Such sampling errors in gastric biopsies may explain the conflicting results on this subject appearing in the literature.

Gastrectomy↗

PubMed1996

Histologic classification of endoscopically removed flat colorectal polyps: a multicentric study.

A total of 594 flat colorectal polyps, removed at endoscopy, were histologically classified into non-neoplastic (n = 49) and neoplastic (n = 545) polyps. Non-neoplastic polyps were subdivided into metaplastic (n = 45) and hyperplastic (n = 4), whereas neoplastic polyps were subdivided into adenomas (n = 481), intramucosal carcinomas (n = 28) and invasive adenocarcinomas (n = 36). Several adenoma phenotypes were discerned: tubular (n = 375), serrated (n = 59), villous (n = 39), mixed (n = 7) and fenestrated (n = 1). Intramucosal carcinomas were subdivided into tubular (n = 26) and serrated (n = 2), and invasive adenocarcinomas into tubular (n = 32), serrated (n = 3) and fenestrated (n = 1). The microscopic characteristics of each histologic phenotype described in this communication are defined and illustrated.

Adenoma↗

PubMed1996

Histopathological study of stromal smooth muscle cells in fibroadenoma of the breast.

Smooth muscle cells are extremely rare stromal components of fibroadenoma. Eighty-five cases of fibroadenoma were reviewed in order to investigate the frequency of smooth muscle cells and to discuss its origin. Of the 85 cases, four (4.7%) cases showed smooth muscle cells in the stroma. Distribution in terms of age and tumor size did not show any difference from other cases. Three cases were classified as an intracanalicular subtype, and one was a mastopathic subtype. The cells possessed most of the ultrastructural characteristics of smooth muscle cells, but poor indentation of nuclear contours suggested the last remnant of fibroblasts. It was therefore easy to recognize the cells derived from fibroblasts. In two of four cases, smooth muscle cells were observed in the stroma, which had marked hyalinization and calcification. Therefore, it was supposed that smooth muscle cells could appear in the stroma of long-standing tumors.

Adolescent↗