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Biomedical subjects

M Kurihara

Publications and source records attributed to M Kurihara.

At least 73 records · Page 4Linked to original sources

An autopsy case of atypical adrenoleukomyeloneuropathy in childhood.

Adrenoleukomyeloneuropathy (ALMN) usually occurs in adulthood, it being extremely rare in childhood. We reported a quite atypical clinical case of ALMN as a variant of adrenoleukodystrophy (ALD). The onset was at 5 years 7 months and ataxia was the major symptom. His condition progressed rapidly to a vegetative state within 1 year. At the age of 11 years and 11 months he died of pneumonia and an autopsy was performed. We herein reported the neuropathological findings in this rare case. The autopsy revealed marked atrophy with diffuse demyelination and astrogliosis throughout the cerebrum, cerebellum and brainstem. Massive degeneration of the pyramidal tracts and loss of neurons were also seen in the spinal cord. The adrenal cortex showed marked atrophy with a striated cytoplasm in ballooned cells. These findings include pathological characteristics of both ALD and adrenomyeloneuropathy (AMN), suggesting ALMN. However, diffuse demyelination with gliosis in the cerebrum and cerebellum is quite atypical for ALMN. They might explain his atypical clinical course, especially the early onset of the disease with ataxia and rapid deterioration.

Adrenoleukodystrophy↗

Gastric adenomas and superficial adenocarcinomas display distinct patterns of mucin carbohydrate and core protein expression.

AIMS: To investigate the histogenetic relationship between gastric epithelial neoplasms we studied differences in expression of mucin carbohydrate antigens and mucin core protein, in normal and metaplastic gastric mucosa, and in gastric adenomas and superficial adenocarcinomas. METHODS AND RESULTS: We generated four monoclonal antibodies, including HGM72/75 against human gastric mucin and HCM14/21 against human colonic mucin, and investigated immunoreactivities of these antibodies and MUC2 protein expression in normal and metaplastic gastric mucosa, adenomas (15 samples) and superficial adenocarcinomas (intestinal-type, 77; diffuse-type, 59 samples). HGM72 reacted with mucous neck cells of the fundic glands and with pyloric glandular cells whereas HGM75 stained foveolar cells and metaplastic goblet cells. Weak binding of HCM14/21 and strong staining with MUC2 were found in metaplastic goblet cells. Binding of HGM75, HCM14, MUC2, but not HGM72 was high in adenomas. An equivalent staining with HGM72 and HGM75 with low expression of MUC2 and HCM14 was shown in intestinal-type carcinomas while the diffuse-type demonstrated more strong reactivity with HGM75 than with HGM72, MUC2 and HCM14. Little binding of HCM21 was observed in any specimens. CONCLUSIONS: This study demonstrates that adenomas predominantly have a intestinal phenotype, but both types of adenocarcinomas retain some cells with a gastric phenotype during the early steps of neoplastic development.

Adenocarcinoma↗

Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 Cooperative Gastric Cancer Study Group.

PURPOSE: To assess the efficacy and safety of S-1, a novel oral fluoropyrimidine derivative, we conducted a multicenter late phase II study in patients with advanced gastric cancer. PATIENTS AND METHODS: Fifty-one patients who had received no previous chemotherapy were enrolled. Fifty patients were eligible for efficacy and safety analyses. The overall response was evaluated for the 43 patients who had metastatic lesions. S-1 was administered orally after breakfast and dinner for 28 days, followed by a 14-day break. The dosages were assigned according to the patients' body surface area (BSA): BSA <1.25 m(2), 40 mg; 1.25-1.5 m(2), 50 mg, and BSA > or =1.5 m(2), 60 mg, twice daily. RESULTS: The overall response to treatment was evaluated as partial response in 19 of the 43 patients (44%; 95% confidence interval 30-59%). The median survival time in all patients was 207 days with 1- and 2-year survival rates of 36.0 and 14.0%, respectively. Grade 3 adverse reactions included decreased hemoglobin values in 2 patients, leukopenia, neutropenia and diarrhea in 1 patient each. No other grade 4 or unexpected adverse reactions were seen. CONCLUSIONS: S-1 is effective against advanced gastric cancer. This oral treatment is suitable for outpatients because of its mild toxicity. Further therapeutic benefits are likely to be obtained by combining S-1 with other chemotherapeutic agents.

Administration, Oral↗

Synthesis, conformation, and chemical properties of new mini parallel double-stranded peptides conjugated with -Phe-Phe- and -Phe-Phe-X-sequences.

To investigate the chemical conformations and functions of the -Phe-Phe-Val- or -Phe-Phe- sequences contained in the Alzheimer's disease related beta-amyloid peptide, a series of mini parallel double-stranded peptides conjugated with two peptide residues to one spacer were designed and prepared. The structure of the compounds was elucidated by circular dichroism (CD) spectrum and NMR two dimensional (2D) nuclear Overhauser enhancement and exchange spectroscopy (NOESY) measurments. The structure of 1,2-ethano-bis(L-Phe-L-Phe-L-Leu), 1,12-dodecano-bis(L-Phe-L-Phe-L-Leu), 1,12-dodecano-bis(L-Phe-L-Phe-L-Val), and 1,12-dodecano (D-Phe-D-Phe-D-Leu) conjugated with L-Leu and L-Val residues show a beta-turn-like nucleation. The dihedral angles (theta = +75 degrees, omega = +180 degrees, phi = +90 degrees, phi = -87 degrees, psi = +180 degrees) obtained from experimental coupling constant (J) data, etc. support that 1,12-dodecano-bis(L-Phe-L-Phe) adopts beta-turn mimic nucleation. The 1,12-dodecano- bis(L-Leu-L-Leu-L-Phe), 1,12-dodecano-bis(L-lle-L-Phe-L-Leu), and 1,12-dodecano-bis(L-Phe-L-Val-L-Leu), etc. adopt most probably a random structure by CD studies. It was found by titration spectrum that an inclusion complex of 1:1 ratio (association constant; azobenzene (guest, Ka=1.0 x 10(4)M-1) is formed between 1,12-dodecano-bis(L.-Phe-L-Phe-L-Leu) and [L0]=1.758 x 10(-5)M-1). Moreover, the stability of the complexes was increased in order of 1,12-dodecano-bis(L-Phe-L-Phe-L-Leu) x azobenzene> 1,12-dodecano-bis(L-Phe-L-Phe-L-Val) x azobenzene> 1,12-dodecano-bis(L-Phe-L-Val-L-Leu) azobenzene. The data show that X-Phe-L-Phe-L-spacer(S)-L-Phe-L-Phe-X (X=amino acids; S = 1,2-ethano- and 1,12-dodecano-) plays an important role as a binding site of the artificial receptor. The hydrophobic interaction of the four Phes in the two strands is a very interesting issue in the physiological action of proteins as well as the conformation of the backbone of X-L-Phe-L-Phe-spacer(S)-iL-Phe-l.-Phe-X.

Amyloid beta-Peptides↗

Thyroid-stimulating antibody in a patient with euthyroid Graves' disease.

We report an 11-year-old girl with euthyroid Graves' disease. She was referred to our clinic because of left exophthalmos without other symptoms suggestive of hyperthyroidism. Her serum concentration of free thyroxine (FT4) and free triiodothyronine (FT3) were normal, but thyroid-stimulating hormone (TSH) was below normal and impaired TSH response to TSH releasing hormone (TRH) was found. Although the sera were positive for anti-TSH receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb), both titers were not as high as usually observed in Graves' disease. Three months later, she developed hyperthyroidism and was treated with propylthiouracil. Within 2 weeks of the initiation of therapy, all symptoms except exophthalmos disappeared, and after 2 months of treatment TRAb was negative though TSAb remained positive. TSAb is therefore a good indicator to use in the diagnosis and follow-up of euthyroid Graves' disease and should be measured in patients with exophthalmos of unknown origin, even in children.

Antithyroid Agents↗

[Traumatic brain injury in children].

We investigated the prognosis of 42 children with traumatic brain injuries. The main etiology was a traffic accident in 46 cases, especially during walking and bicycling, and child abuse in 7 cases. Eighteen cases of acute subdural hematoma 18 cases distributed at all ages, 9 cases of diffuse axonal injury mainly during school age, 4 cases of chronic subdural hematoma under 2 years. These were all caused by child abuse. Fifteen cases showed a good prognosis with independent activities of daily living (ADL). The main type of injury was diffuse axonal injury in this group. Twelve cases showed a bad prognosis with completely dependent ADL. The bad prognostic factors were chronic subdural hematoma caused by child abuse, consciousness loss with Glasgow Coma Scale less than 8 or lasting more than 2 weeks. After rehabilitation in our hospital, 37 cases returned to school: an ordinary class in 20 cases, a special class in an ordinary school in 5 cases and a special class in 12 cases. About half of the cases returned to an ordinary class, although with problems such as learning difficulty, danger and bullying.

Accidents, Traffic↗

[Two cases of acute aortic disease complicated by ischemic cerebrovascular disease].

Ischemic cerebrovascular diseases are commonly induced by atherosclerosis and cardiogenic embolization but rarely they occur in association with Takayasu's arteritis and aortic lesion such as aortic dissection and aneurysm. Here we experienced two cases of acute aortic disease complicated by ischemic cerebrovascular disease (CVD). Patient 1 was a 77-year-old male. He complained of dyspnea and left hemiparesis. He was brought to our hospital by ambulance. Left hemiparesis and dyspnea improved soon. The patient only complained of left lower extremity pain and physical examination revealed hypotension. Brain CT showed no abnormality but chest CT revealed aortic dissection. The resection of the intimal tear and replacement of ascending aorta and aortic arch with 28 mm Hemashield graft were performed under hypothermia and selective cerebral perfusion. The postoperative course was uneventful and he has been doing well. Patient 2 was a 67-year-old female. She was found lying unconscious and brought to our hospital by ambulance. Physical examination revealed right hemiparesis and hypotension. Brain CT demonstrated low density area in the left corona radiata and ruptured aortic aneurysm was seen in abdominal CT. Just after the examination, the patient suddenly complained of severe back pain and died despite cardiopulmonary resuscitation. Aortic lesions can manifest ischemic symptom involving multiple organs following their vascular disorder. Aortic dissection rarely occurs in association with ischemic CVD and in that case it is likely to be seen by neurologists. Aortic dissection and aneurysm deteriorate so suddenly that immediate diagnosis and proper treatment are needed.

Acute Disease↗

[Absence of cross resistance between an irinotecan plus cisplatin combination and raltitrexed (ZD1694) in two patients with advanced colorectal cancer].

Two patients with advanced colorectal cancer were consecutively administered two different chemotherapeutic regimens. The first patient showed an initial response to combination treatment with irinotecan plus cisplatin, but then progressed. He subsequently responded to treatment with a novel thymidylate synthase (TS) inhibitor, raltitrexed. The second patient, who progressed after exhibiting a response to raltitrexed, subsequently responded to irinotecan/cisplatin combination therapy. In conclusion, no clinical cross resistance between the regimens of irinotecan/cisplatin combination therapy and raltitrexed was observed in these patients with advanced colorectal cancer.

Antimetabolites, Antineoplastic↗

[A case of juvenile bow hunter's stroke].

Bow hunter's stroke results from vertebrobasilar insufficiency caused by mechanical occlusion or stenosis of the vertebral artery at the C 1-2 level on head rotation. Commonly it is seen in elder people with cervical spondylosis. Here we reports a case of bow hunter's stroke in a 25-year-old male who complained of visual disturbance and syncope on rotation of the head 90 degrees or more to the left. This problem was frequently seen on driving a car. A cervical x-ray and MRI of the head revealed no abnormal findings such as atlantoaxial dislocation. Angiograms demonstrated obstruction of the right vertebral artery at the C 1-2 level on left rotation of the head. The hemodynamics on the circle of Willis were evaluated and surgical treatment was planned. The posterior fusion involving C 1-2 has long been used to limit atlantoaxial rotational movements. However, it has the serious disadvantage because the range of head motion is severely reduced. Recently decompression of the atlantoaxial portion of the affected vertebral artery has been used, but recurrence of occlusion with head rotation can be seen postoperatively. Since the patient could predict the onset of attack, we managed him conservatively, and no traffic accident reported during this period of observation. Due to several surgical disadvantages, we propose that whenever possible, patients with bow hunter's stroke should be managed conservatively especially in young patients.

Adult↗

[Two sibling patients with non-Fukuyama type congenital muscular dystrophy with low serum selenium levels--therapeutic effects of oral selenium administration].

We report a pair of siblings with non-Fukuyama type, merosin-positive congenital muscular dystrophy, born to unrelated parents. Patient 1 was a 16-year-old girl with myopathy, cardiomyopathy, severe mental retardation and epilepsy. Patient 2 was a younger brother of patient 1, a 10-year-old boy with myopathy, severe mental retardation and epilepsy. Their serum selenium levels were decreased to 25 micrograms/l and 55 micrograms/l, respectively (normal 97-147 micrograms/l). Their muscle biopsy findings were similar to those seen in selenium deficient myopathy, showing abnormal mitochondrial distribution and giant mitochondria. After oral administration of selenium for 3 months, their gait disturbance apparently improved, which was confirmed by a gait analysis system. Why their gait improved remain unclear, but a defect in selenium metabolism may play a role in the development of congenital muscular dystrophy and mental retardation.

Administration, Oral↗

A case of congenital afibrinogenemia: fibrinogen Hakata, a novel nonsense mutation of the fibrinogen gamma-chain gene.

Congenital afibrinogenemia due to a novel homozygous nonsense mutation of the fibrinogen gamma-chain gene, fibrinogen Hakata, was found in an 18-year-old Japanese girl who had received supplemental fibrinogen therapy since she was 4 months old. The plasma fibrinogen concentrations of the proband were measured as less than 10 mg/dl by a functional method and less than 17 mg/dl by an immunological method. Fibrinogen concentrations of her family were in the range of 94-164 mg/dl. The proband and her family had no other clinical symptoms. Genomic DNA of the proband and her family was isolated from leukocytes, and all exons of fibrinogen subunits and their intron/exon boundaries were analyzed. A genetic mutation, a guanine-to-thymine (G-to-T) transversion at the nucleotide position of 5860, was identified on exon 7 of the gamma-chain gene. This mutation changed the codon for the 231st residue of the gamma-chain from GAG (Glu) to TAG (stop). No other mutation was observed. Aalpha, Bbeta and gamma chains were observed in plasma of the heterozygous family members. However, only a trace amount of Aalpha chain and no gamma chain was detected in the plasma of the proband.

Afibrinogenemia↗

[Chorioretinal blood flow changes following acupuncture between thumb and forefinger].

PURPOSE: To evaluate the effects of acupuncture stimuli on general circulation and chorioretinal blood flow changes, and to determine the duration of effect and the learning effect. OBJECTS AND METHODS: Twelve healthy young volunteers were divided into two groups. One had no experience of acupuncture (Non-Experience group); the other had experience of acupuncture (Experience group). Hegu (LI 4) between thumb and forefinger was acupunctured. Chorioretinal blood flow was measured via Heidelberg retina flowmeter before, during, and after acupuncture stimuli. RESULTS: In both groups, chorioretinal blood flow increased significantly during stimuli, with continuous bradycardia. The Experience group showed greater changes than the Non-Experience group. CONCLUSIONS: Chorioretinal blood flow was increased through relative parasympathetic reaction by stimulating an acupuncture point. Acupuncture is a promising adjunctive therapy for ischemic ocular diseases.

Acupuncture Therapy↗

Mechanistic studies of catechins as antioxidants against radical oxidation.

The antioxidative mechanisms of catechins were studied by investigating products generated at the first stages by 2, 2'-azobis(2-aminopropane)hydrochloride (AAPH)-induced radical oxidation, without any isolation, using LC/MS, spectrophotometry, and PM3 semiempirical molecular orbital (MO) calculations. Catechins were quite effective in scavenging peroxyl radicals in a liposomal system and in an aqueous system except for (-)-epigallocatechin (EGC). EGC was the least effective among four catechins tested. From the results of LC/MS and spectroscopic studies, (-)-epicatechin (EC) would be gently converted to an anthocyanin-like compound. According to the mechanisms, the compound produced from EC by radical oxidation can also function as an antioxidant. As a result, EC has a longer inhibition period (tinh = 9360 s). On the other hand, EGC decreased shortly after oxidation (tinh = 3420 s) and was transformed to a quinone-like compound. The addition of superoxide dismutase (SOD) reduced the chemiluminescence from EGC during oxidation. Active oxygen including superoxide anion radicals (O-2) may be produced in the case of EGC, but not in the case of EC. However, EGC has a more rapid scavenging effect on peroxyl radicals (kinh/kp = 232) than EC (kinh/kp = 41). The calculated C-H bond dissociation enthalpies (BDEs) for catechins at the C-2 position were unexpectedly low (65 kcal/mol) compared to O-H BDEs at phenolic sites (70 kcal/mol), suggesting that hydrogen at the C-2 position may be abstracted by free radicals. The authors propose the tentative antioxidative mechanisms of catechins depending on the experimental results and theoretical calculations.

Amidines↗

Determination of 4-hydroxy-2-nonenal in primary rat hepatocyte cultures by liquid chromatography with laser induced fluorescence detection.

An HPLC (high performance liquid chromatography) method with laser induced fluorescence (LIF) detection is described for the determination of 4-hydroxy-2-nonenal (HNE) formed from lipid peroxidation in rat hepatocytes. Carbonyl compounds were fluorescently labelled by incubating the hepatocyte samples with a tagging reagent, 4-(2-carbazoylpyrrolidin-1-yl)-7-nitro-2,1,3-benzoxadiazole (NBD-ProCZ), at 60 degrees C for 10 min. The hydrazone derivatives were extracted with a C18 solid phase extraction (SPE) cartridge and separated on a reversed-phase HPLC column. The detection limit was 2.5 fmol or 0.5 nM (5 microL injection) of HNE in the cell homogenate. Method precision (C.V.) was 5% at the 5 nM level. The method has been used to determine free HNE in rat hepatocyte samples treated with several pro-oxidant toxins. A significant HNE increase (from 4 to 27.6 pmol/10(6) cells) was observed with the samples treated by allyl alcohol. The results were in accordance with those for malondialdehyde formation as measured by a thiobarbituric acid (TBA) assay.

Aldehydes↗

Urotensin II is the endogenous ligand of a G-protein-coupled orphan receptor, SENR (GPR14).

Two molecular species of urotensin II (UII) were isolated from porcine spinal cords and identified as the endogenous ligands of a G-protein-coupled orphan receptor, SENR (sensory epithelium neuropeptide-like receptor), which is identical to GPR14. We established a CHO cell line stably expressing the rat SENR and investigated several tissue extracts to evoke the response mediated by the SENR. Extract from porcine spinal cords showed an activity of arachidonic acid metabolites release from SENR-expressing cells and was purified using HPLC. Two active substances were isolated and their sequences were determined as GPTSECFWKYCV and GPPSECFWKYCV, which were revealed to be porcine UII. Synthetic UII peptides caused arachidonic acid metabolites release activity in the rat SENR-expressing cells with an EC(50) value of 1 nM. Three cDNAs encoding the precursor proteins of porcine UII were cloned from a porcine spinal cord cDNA library; 2 consist of 121 amino acid residues and the other, which seemed to be a splicing variant, consist of 85 residues.

Amino Acid Sequence↗

Scavenging mechanisms of (-)-epigallocatechin gallate and (-)-epicatechin gallate on peroxyl radicals and formation of superoxide during the inhibitory action.

The scavenging effects of (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) on peroxyl radicals and their mechanisms were studied by investigating the products formed during the first stages by 2,2'-azobis(2-aminopropane) hydrochloride (AAPH)-induced oxidation, without any isolation, using LC/MS, spectrophotometry, chemiluminescence analyses, and semiempirical molecular orbital (MO) calculations. The results show that EGCG can be converted to an anthocyaninlike compound followed by cleavage of the gallate moiety by oxidation. On the other hand, ECG can be converted to an anthocyaninlike compound after cleavage of the gallate moiety. The calculated C-H bond dissociation enthalpies (BDEs) for EGCG and ECG at the C-2 position were quite low (62.7 and 66.8 kcal/mol, respectively) compared with O-H BDEs at the phenolic sites (ca. 70 kcal/mol), suggesting that the C-2 hydrogen can be abstracted by free radicals. The addition of superoxide dismutase (SOD) decreased the chemiluminescence in EGCG by one-half during the inhibitory action. Active oxygen including superoxide (O2-) would be produced in EGCG, but not in ECG. The authors proposed the antioxidative mechanisms of EGCG and ECG depending on the experimental results and theoretical calculations.

Amidines↗

Phase II study of docetaxel in patients with metastatic pancreatic cancer: a Japanese cooperative study. Cooperative Group of Docetaxel for Pancreatic Cancer in Japan.

Docetaxel has been reported to show promising anti-tumour activity in pancreatic ductal cancer (PC). This study was conducted to evaluate the activity and toxicity of moderate-dose (60 mg m(-2)) docetaxel in Japanese chemo-naive patients with measurable metastatic PC. The patients had a performance status of 0-2. They received docetaxel intravenously over a 1- to 2-h period without any premedication for hypersensitivity reactions. This treatment was repeated every 3-4 weeks with dose adjustments based on the toxic effects observed. Twenty-one patients were eligible and treated with docetaxel. The median number of courses was 2 (range, 1-4). None of the patients achieved an objective response; seven showed no change and 13 showed progressive disease. In one patient, the response was not assessable because of early death. The median survival time for all patients was 118 days. The main grade 3-4 toxicities by patient were leucocytopenia (67%) and neutropenia (86%). Other grade 3-4 toxicities included anaemia (10%), thrombocytopenia (5%), nausea/vomiting (29%), anorexia (29%), GOT/GPT increase (10%), alkaline phosphatase increase (14%), malaise/fatigue (33%) and alopecia (24%). In conclusion, docetaxel, administered on this schedule, did not show significant anti-tumour activity in patients with metastatic PC.

Adult↗