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Biomedical subjects

K Sakamoto

Publications and source records attributed to K Sakamoto.

At least 577 records · Page 32Linked to original sources

[A case of Down syndrome with chronic renal failure caused by long-term asymptomatic hyperuricemia].

The elevation of serum urate levels in patients with Down syndrome has been reported by several investigators, but gout or renal dysfunction due to hyperuricemia has rarely been encountered. We described a case of Down syndrome showing chronic renal failure caused by long-term asymptomatic hyperuricemia. A 30-year-old man, who had persistent subclinical hyperuricemia for nine years, was noted to have pale face, weakness and hypertension. Laboratory findings revealed acute renal dysfunction. He died from uremic lung 7 months later. Autopsy disclosed a finding suggesting chronic urate nephropathy; many gouty microtophi with foreign body reaction in the renal medulla. It is important to estimate serum urate and to control increased serum urate level in order to prevent from renal dysfunction in Down syndrome.

Adult↗

[Effect of ethanol on isometric tone of aorta from guinea pig].

Using aortic strips isolated from guinea pig, effects of ethanol on vascular smooth muscle tone were studied. Low concentrations (5, 50, 100 mM) of ethanol potentiated norepinephrine and serotonin-induced contractions, but not KCl-induced one. Ethanol (100 mM) potentiated calcium-induced contraction in the presence of norepinephrine, but not that in the presence of KCl. Ethanol (100 mM) showed no effects on norepinephrine-induced contraction in the calcium-free medium. Ethanol (100 mM) augmented 45Ca uptake stimulated with norepinephrine, but not that with KCl. Ethanol at the higher concentration of 600 mM by itself induced contraction, which was inhibited by trifluoperazine or in the calcium-free medium, but not by phentolamine, diphenhydramine, methysergide, indomethacin or nifedipine. Ethanol (600 mM) directly increased 45Ca uptake, which was not affected by nifedipine. These findings indicate that the low concentrations of ethanol potentiate receptor-mediated vascular smooth muscle contraction and the higher concentration of ethanol directly contracts it via facilitation of transmembranous calcium influx.

Animals↗

[Improvement of intractable nocturnal asthma treated by therapeutic awakening].

A 33-year-old female was admitted to our hospital because of intractable asthma which had not been improved by intensive treatment at another hospital. Her asthmatic attacks were improved within a week by treatments including systemic corticosteroids and mechanical ventilation. However, in a few weeks nocturnal asthma recurred frequently, and it was resistant to various bronchodilators and steroids. Therapeutic awakening, that is, awakening the patient quietly at 3 a.m. with inhalation of 2.5 mg salbutamol was started. Her symptoms and physical findings rapidly improved thereafter. It was concluded that therapeutic awakening may be effective for the treatment of refractory morning dipping of asthma.

Adult↗

Relative mitogenic activities of wild-type and retinoblastoma binding-defective SV40 T antigens in serum-deprived and senescent human diploid fibroblasts.

A novel gene transfer approach was used to investigate whether the retinoblastoma (Rb)-binding domain of simian virus 40 (SV40) T antigen is required for efficient T antigen-mediated stimulation of DNA synthesis is quiescent or senescent human embryo fibroblasts. In senescent cells, comparison between wild-type T antigen and a mutant defective in Rb binding (Glu-107-->Lys) revealed the latter to have approximately 15-fold lower activity. In contrast, comparison of wild-type and Rb- T antigens in serum-deprived quiescent cells revealed a much smaller (1.8-fold) difference. Surprisingly, an 18-fold differential could be induced by treating quiescent cells with the differentiating agent sodium butyrate. These results suggest that the role of Rb in control of the cell cycle is strongly dependent on the physiological state of the cell and the mechanism of growth arrest.

Antigens, Polyomavirus Transforming↗

[Long-term clinical course of sequelae in patients with neonatal anoxic encephalopathy resulting in profound mental retardation and motor disturbance].

A long-term observation has been made in 58 patients (30 males and 28 females) with severe sequelae of neonatal anoxic encephalopathy. They aged from 8 months to 65 years. All of them had motor disturbances and profound mental retardation. Motor function was improved in 4 patients with aging. In contrast, motor activity deteriorated in 11 cases, of which 4 showed a mental regression. Among them, patients who had originally better motor ability than sitting were likely to deteriorate by uncontrollable epilepsy and/or excessive administration of anticonvulsants. Regression of the patients with worse motor ability like bedridden appeared to attributable hypertonia of muscles and bodily deformation. Fifteen cases showed an exacerbation of general condition which originated predominantly to respiratory distress. Twelve patients died including 6 exacerbated cases. Exacerbation or death may have occurred frequently in specific periods of infancy, adolescence and youth with the patients who showed very low motor function such as bedridden and no locomotion.

Adolescent↗

[Phase I Study of RA-700. RA-700 Clinical Study Group].

An antitumor substance, RA-700, isolated from Rubia akane or Rubia cordifolia has the novel structure. Phase I clinical study was conducted by the RA-700 clinical study group consisting of 6 institutions. A single dose administration and 5-day schedule administration were evaluated with 14 patients respectively. RA-700 was given from 0.2 to 1.4 mg/m2 in single i.v. dose study, from 0.4 to 2.0 mg/m2 in 5-day i.v. schedule study. Nausea and vomiting, fever, stomachache, mild hypotension and slight abnormality of electric-cardiogram were observed as the toxicities. In pharmacokinetic study, the elimination half-lives (t1/2) of RA-700 in plasma were 55 min, of alpha-phase and 3.9 hrs. of beta-phase by single dose study, and 23-25 min. of alpha-phase and 6-14 hrs. of beta-phase by 5-day schedule study. Accumulation was not found by 5-day schedule administration, and metabolite were not observed in plasma and urine. It seems that RA-700 is metabolized by the liver and excreted in the feces. In conclusion, the maximum tolerated dose was 1.4 mg/m2 for 5-day schedule administration.

Adenocarcinoma↗

Two different types of cell loss patterns of murine tumors and their corresponding histological findings and possible mechanisms of production of hypoxic cells.

Cell loss patterns of five tumors and their histological findings were investigated in WHT/Ht strain mice. The tumors investigated were squamous cell carcinoma H, squamous cell carcinoma NOS, squamous cell carcinoma TAK, rhabdomyosarcoma KAS, and fibrosarcoma YAS. The present study revealed that histological findings of tumor tissues are not necessarily corded structure presented by Thomlinson and Gray. The five were divided into two groups according to their histological findings, i.e. a corded structure (squamous carcinoma H and NOS) and a non-corded structure (squamous cell carcinoma TAK, rhabdomyosarcoma KAS and fibrosarcoma YAS). The cell loss patterns (125I-iododeoxyuridine retention curves) were also divided into two groups which corresponded to the histological structures. Two tumors with the corded structure (squamous cell carcinoma H and NOS) have a cell loss pattern with a constant shoulder portion (a migration time of tumor cells through a tumor cord from capillary to necrotic region). In these tumors, the cell loss occurred in the necrotic regions. In the other tumors with the non-corded structure, cell loss curves have no constant shoulder portion and cell loss might occur throughout the tumor. The origin of hypoxic cells in these two types of histology are presumably different. The diffusion-limited hypoxia, i.e. chronically hypoxic cells, may be the main cause for the tumors with corded structure. On the other hand, hypoxia as a result of temporary cessation of blood flow within the tumor vasculature, i.e. acutely hypoxic cells, may mainly occur in the tumor with non-corded structure.

Animals↗

Role of leucine residues in the C-terminal region of human interleukin-6 in the biological activity.

Site-directed mutagenesis of two sets of three periodic leucine residues which appear at every seventh position in the C-terminal region of human interleukin-6 (IL-6) was performed. Both receptor-binding and immunoglobulin (Ig)-induction activities of a triple mutant Leu168,175,182-->Val were only 1% compared with those of wild-type IL-6. However, the mutant Leu152,159,166-->Val had 13% receptor-binding and 2% Ig-induction activities of those of wild-type IL-6. In order to obtain more direct information on the receptor-binding region, we prepared two synthetic peptides. A significant binding activity was observed for the peptide Leu168-Met185, but not for the peptide Leu152-Arg169. These results indicate that leucine residues in the C-terminal region, especially Leu168, Leu175, and Leu182, play an important role in the receptor-binding and Ig-induction activities.

Amino Acid Sequence↗

Purification and characterization of a novel lactonohydrolase, catalyzing the hydrolysis of aldonate lactones and aromatic lactones, from Fusarium oxysporum.

A novel lactonohydrolase, an enzyme that catalyzes the hydrolysis of aldonate lactones to the corresponding aldonic acids, was purified 10-fold to apparent homogeneity, with a 61% overall recovery, from Fusarium oxysporum AKU 3702, through a purification procedure comprising DEAE-Sephacel, octyl-Sepharose CL-4B and hydroxyapatite chromatographies and crystallization. The molecular mass of the native enzyme, as estimated by high-performance gel-permeation chromatography, is 125 kDa, and the subunit molecular mass is 60 kDa. The enzyme contains 15.4% (by mass) glucose equivalent of carbohydrate, and about 1 mol calcium/subunit. The enzyme hydrolyzes aldonate lactones, such as D-galactono-gamma-lactone and L-mannono-gamma-lactone, stereospecifically. Furthermore, it can catalyze the asymmetric hydrolysis of D-pantoyl lactone, which is a promising chiral building block for the chemical synthesis of D-pantothenate. These reactions are reversible, and the reaction equilibrium at pH 6.0 has a molar ratio of nearly 1:1 with D-pantoyl lactone and D-pantoic acid. The Km and Vmax for D-galactono-gamma-lactone are 3.6 mM and 1440 U/mg, respectively, and those for D-galactonate are 52.6 mM and 216 U/mg, respectively. The enzyme also irreversibly hydrolyzes several aromatic lactones, such as dihydrocoumarin and homogentisic-acid lactone.

Amino Acid Sequence↗

[A case of Cushing syndrome caused by ACTH producing atypical lung carcinoid tumor].

A forty-one-year-old male who was found to have lung carcinoid tumor showed clinical features of Cushing syndrome. At the age of 38 years during a regular check-up, a chest roentgenogram showed multiple nodular shadows in the bilateral lung, and he was admitted to hospital. By open lung biopsy, he was diagnosed as having malignant carcinoid or small cell carcinoma of the lung. The abnormal lung shadows did not respond to chemotherapy (CDDP + VDS). The clinical course after discharge was uneventful until the age of 41 years, when he was readmitted to our hospital because of brain metastasis. Physical examination revealed moon face and central obesity. Plasma ACTH level was high and dexamethasone suppression test showed no cortisol suppression on 8 mg dexamethasone administration. Therefore, it was thought that the patient had ACTH producing ectopic tumor which led to Cushing syndrome. We measured the molecular weight of ACTH by column chromatography and found he had a big ACTH (molecular weight about 22,000). Reexamining him clinically and histologically, we concluded that the patient had atypical carcinoid tumor in the lung which might produce ACTH causing Cushing syndrome with metastasis to the brain.

Adrenocorticotropic Hormone↗

Low-dose rate telecobalt therapy as a boost against esophageal carcinomas.

The results of treating 54 esophageal carcinomas with low-dose rate telecobalt therapy (LDRT) as a boost were compared with those of treating 97 esophageal carcinomas with conventionally fractionated irradiation alone (CFI). The LDRT (100 cGy/hr, 500 to 700 cGy/day, a total dose of 1400 to 2000 cGy) was boosted at 10 days after 6000 cGy of the CFI dose. Although the LDRT group included more advanced cases than the CFI group, local effects and survival rates in the former group were slightly better than in the latter group. Late complications were more severe in the LDRT group. However, they were acceptable when the total dose administered to this group was less than 8000 cGy. Using LDRT as a boost against esophageal carcinomas was found to be satisfactory therapeutically.

Adenocarcinoma↗

Traumatic cervical syringomyelia related to birth injury.

A rare case of cervical syringomyelia related to breech delivery is reported. The initial diagnosis was bilateral brachial plexus palsy due to birth injury, which was revealed by magnetic resonance imaging (MRI) to be traumatic syringomyelia. The usefulness of MRI in the early diagnosis of cervical cord birth injury, especially in differentiating between brachial plexus palsy due to birth injury and spinal cord trauma due to birth injury in infancy, is emphasized.

Birth Injuries↗

MRI of anterior spinal artery syndrome of the cervical spinal cord.

Cervical spinal cord lesions in the anterior spinal artery syndrome were delineated on magnetic resonance images (MRI) in four patients. The lesion was always seen anteriorly in the cervical cord. On T2-weighted images, the lesions appeared hyperintense relative to the normal spinal cord, while on T1-weighted images, two chronic lesions appeared hypointense, with local atrophy of the cord. In one case, repeated T1-weighted images showed no signal abnormality 4 days after the ictus, but the lesion became hypointense 18 days later, when contrast enhancement was also recognized after injection of Gd-DTPA; this sequence of intensity changes was similar to that of cerebral infarction. The extent of the lesion seen MRI correlated closely with neurological findings in all cases. Although the findings may not be specific, MRI is now the modality of choice for confirming the diagnosis in patients suspected of having an anterior spinal artery syndrome.

Adult↗

Retrograde filling of the anterior choroidal artery: vertebral angiographic sign of obstruction in the carotid system.

Retrograde filling of seven anterior choroidal arteries from the posterior circulation was observed on a vertebral angiogram in six patients with occlusion of the proximal anterior choroidal artery or of the internal carotid artery. In one patient with thrombotic occlusion of the internal carotid artery, the enlarged anterior choroidal artery functioned as a major collateral pathway from the posterior circulation to the territory of the middle cerebral artery. Retrograde filling of the anterior choroidal artery is a sign of obstruction changes in the ipsilateral carotid artery at or proximal to the origin of the anterior choroidal artery.

Adolescent↗

Radiographic features in ischemic jejunoileitis: serial changes and comparison with pathologic findings.

Serial radiographic examinations of the small intestine, including double-contrast studies, were performed in 13 patients with ischemic jejunoileitis, nine with the stricturing form and four with the transient form. Thumbprinting was observed in five (38%) patients and thickening of the folds in four (31%) at the acute stage of the disease. Tubular narrowing with irregular contours and dilated proximal bowel was observed in six (46%) patients and appeared on day 27 or later. Pathologic findings of the resected specimen in eight patients with the stricturing form revealed annular stricture with relatively shallow ulcers; the irregular contours of the tubular narrowing on radiographs were consistent with a granular or nodular appearance and/or multiple fissures on pathologic study. Eccentric deformity and sacculation were demonstrated in only one patient with the stricturing form. In addition, double-contrast study revealed small ulcers in three (23%) patients. Our results indicate that radiographic findings accurately reflect the clinical course and pathologic findings in this disease.

Adult↗

Interleukin-8 is constitutively and commonly produced by various human carcinoma cell lines.

We examined the production of interleukin-8 and interleukin-6 by 30 human carcinoma cell lines. Serum levels of interleukin-8 were measured in 14 patients with hepatocellular carcinoma by enzyme-linked immunosorbent assay and Northern blotting. Furthermore, serum interleukin-8 was also investigated in a nude mouse bearing a tumor of the HuH7 hepatoma cell line producing interleukin-8. Of the 30 cell lines, 29 (96.7%) constitutively produced interleukin-8, and 19 of the 29 (65.5%) were high producers (> 1 ng/ml culture supernatant). Among the high producers, 4 cell lines released both interleukin-8 and interleukin-6. Interleukin-6 was constitutively produced by 17 of the 30 (56.7%) cell lines, 4 of which (23.5%) were high producers (> 1 ng/ml). By Northern blot analysis, mRNAs of interleukin-8 and interleukin-6 were detected in producing cell lines. Of 14 patients with hepatocellular carcinoma 4 (28.5%) showed increased levels of serum interleukin-8. Furthermore, inoculation of the HuH7 hepatoma cell line which produced the highest amount of interleukin-8 into a nude mouse resulted in tumor production accompanied by an elevated level of human interleukin-8 (646 pg/ml) in the peripheral blood. Thus, interleukin-8 is constitutively and commonly produced by various carcinoma cell lines. The production of interleukin-8 by carcinoma cells may be related to the elevation of serum interleukin-8 in patients with hepatocellular carcinoma. Finally, these cell lines may be valuable for studying the relationship between interleukin-8 and cancer.

Animals↗