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Biomedical subjects

H Sakai

Publications and source records attributed to H Sakai.

At least 793 records · Page 44Linked to original sources

Alternative secondary structures in the phage G4 origin of the complementary DNA strand synthesis: effects of NaCl concentration on the bleomycin-DNA interaction.

The effects of NaCl concentration on bleomycin-induced cleavages of single-strand and double-strand DNA fragments containing the phage G4 origin of complementary DNA strand synthesis were investigated. It was found that bleomycin could be used as a reagent to analyze secondary and tertiary structures and subtle changes of DNA structures. The effects of NaCl concentration on cleavages of single-stranded DNA were distinct at every target site, indicating that the diversity of topolotical properties of DNA might change the selectivity of the bleomycin-induced DNA cleavage. These results showed alternative secondary structures within and close to the G4 origin of complementary DNA strand synthesis.

Bacteriophages↗

Evaluation of airway smooth muscle contractions in vitro by high-frequency ultrasonic imaging.

To visualize ASM contraction in vitro, we measured changes in cross-sectional area and inner circumference of isolated porcine and human bronchi in response to acetylcholine or carbamylcholine chloride (Carbachol) using high-frequency ultrasound. A mechanical ultrasonic catheter (20 MHz; diameter, 1.7 mm; echo element, 1 mm2) demonstrated three histologic layers (mucosa, cartilage and adventitia) and allowed measurement of dose-dependent contraction of porcine bronchi over time. Acetylcholine (10(-4)M) significantly decreased the cross-sectional area by 17 +/- 2.85 percent but did not change the circumference. The mean initial value for area was 0.6 +/- 0.08 cm2 and for circumference was 3.0 +/- 0.24 cm (n = 5). The EC50 of acetylcholine was 1.5 x 10(-8) M. Carbachol (10(-4)M)-induced contractions of human bronchi were also observed under the same conditions. In conclusion, high-frequency ultrasonic imaging can be used to study the morphology of ASM contractions in vitro, providing valuable information on the natural dynamics of ASM.

Acetylcholine↗

Increased frequency of the heterozygous switch region of IgA2 in Japanese patients with IgA nephropathy.

The relation between IgA hyperproduction and restriction fragment length polymorphism (RFLP) of the immunoglobulin heavy chain switch (S) region was examined in Japanese patients with IgA nephropathy (IgAN) using Southern blot hybridization. Polymorphism in the S regions of IgM, IgA1 and IgA2 (SA2) was detected. A significant increase in the frequency of heterozygous phenotype of SA2 was shown in the patients. These patients showed a significant increase in the amount of serum IgA, IgA bearing cells and levels of proteinuria. Although two reports on RFLP of the S region have been published in Europe, the results differed. A comparison of the three reports showed different frequencies in the phenotype of the S region between Caucasian and Japanese patients. These results suggested that there is heterogeneity at the S region in IgAN patients in various countries and that this polymorphism might be associated with IgA hyperproduction and the development of proteinuria in Japanese patients.

Adult↗

Beta(+)-thalassemia with hemochromatosis.

A 64-year-old man was admitted due to ascites. Laboratory data showed hemoglobin 6.7 g/dl, mean corpuscular volume 82 fl, and ferritin 2,360 ng/ml. Liver biopsy showed hemochromatosis. The diagnosis of beta-thalassemia was suggested by a decreased ratio of beta/alpha-globin synthesis in vitro (0.26). Cloning of the beta-globin gene showed A-to-G mutation in the first base of the ATA box. He was confirmed to be homozygous for this specific allele by beta-gene complex analysis and analysis of Southern blot hybridization of the alpha- and beta-globin genes. His two sons were confirmed to be heterozygous for this allele.

Adult↗

An aged patient with Henoch-Schönlein purpura nephritis: a case report and review of the literature.

A 63-year-old patient with Henoch-Schönlein purpura (HSP) nephritis showed progressive proteinuria. Purpura was observed in the extremities as well as in the trunk without any preceding upper respiratory tract infections or drugs, and it disappeared after corticosteroid therapy although mild proteinuria continued throughout the therapy. Renal biopsy specimens showed mesangial IgA deposits in the glomeruli, but no IgA deposits were observed in the dermal vessels or in the intrarenal extraglomerular capillaries. Progressive proteinuria was improved with 37.5 mg/day of captopril. Severity of HSP nephritis in middle-aged to aged patients in the literature was reviewed. It was suggested that careful observation is required in aged patients with HSP nephritis.

Aged↗

Prevention of progressive renal failure by levothyroxine sodium in a diabetic patient with renal insufficiency and hypothyroidism.

The progressive renal failure of a 49-year-old female diabetic patient with renal insufficiency and hypothyroidism was successfully prevented by levothyroxine sodium treatment. Her renal function worsened in parallel with the exacerbation of hypothyroidism. Cessation of progressive renal failure was observed after administration of levothyroxine sodium (0.05 mg daily) for more than 24 months. Mean slopes of reciprocal serum creatinine levels for 12 months before and after the administration of levothyroxine sodium were -1.67 x 10(-3) and +8.68 x 10(-4), respectively. It was suggested that levothyroxine sodium was effective in the prevention of progressive renal failure in this patient.

Diabetic Nephropathies↗

Lupus nephritis associated with bacterial panperitonitis and lung alveolar hemorrhage.

A 36-year-old woman was admitted to the hospital with the diagnosis of nephrotic syndrome due to lupus nephritis. The patient had panperitonitis caused by Staphylococcus aureus as a complication, and an emergency laparotomy was performed. After the operation, the patient developed a massive lung alveolar hemorrhage. Methylprednisolone pulse therapy showed a marked effect on the lung hemorrhage. It is known that lung alveolar hemorrhages associated with systemic lupus erythematosus have a very high mortality; the present case is relatively rare because of the good response to steroid pulse therapy.

Adult↗

New fluorescent probes E3810 and methoxy E3810 for determining distributions of the apical membrane and the acidic compartment of gastric acid secreting cells.

Substituted benzimidazoles such as omeprazole, E3810 and methoxy E3810 were inhibitors of gastric H+, K(+)-ATPase which is rich in the apical membrane of gastric parietal or oxyntic cells at the secreting state. The acid-activated compounds of omeprazole and methoxy E3810, which have methoxy group at the 5-position in the benzimidazole ring, are fluorescent (excitation wavelength = 370 nm; emission wavelength = 560 nm). The fluorescence disappeared when the activated compounds reacted with the ATPase or glutathione. Using this fluorescence property, the distribution of the intracellular acidic canalicular space in isolated single parietal cells was determined. On the other hand, irradiation with ultraviolet light (335 nm) of the acid-activated compound of E3810 which had been reacted with sulfhydryl group of the ATPase or glutathione resulted in a formation of a fluorescent compound (emission = 470 nm). Using this second fluorescence property, we determined the distribution of the apical membrane of the intracellular canaliculus of isolated single mammalian parietal cells and also the location of the apical membrane on the external surface of newt oxyntic cells.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[Apparent depth by the stereograms without binocular retinal disparity: is Lau effect artifact?].

We examined the idea that, when the Zöllner figure in one eye and the principal lines in the figure in the other eye were presented, the perceived depth is due to "phenomenal" disparity. The phenomenal disparity is defined as apparent displacement between two illusory "oblique" principal lines in one eye and two "parallel" principal lines in the other. Observes were asked whether depth was seen or not at upper or lower part of the two perceived lines and, if seen, which line was closer. Seventeen observers showed that only 9% of their responses was consistent with the idea, although they reported depths for disparity stimuli. This suggests that the dichoptic presentation of such figures should not be considered as that requires the processing of binocular disparity.

Adult↗

CD4 subsets in IgA nephropathy.

CD45RA+ (2H4+) and CD45RA-(CD29, 4B4+) antigenic expressions, recognized as a suppressor inducer and a helper inducer, respectively, on CD4+ and T alpha 4+ cells (Fc alpha receptor bearing CD4 T cells) were measured by three color flow cytometry in patients with IgA nephropathy (IgAN). The 4B4+ subsets of CD4 and T alpha 4 T cells were increased significantly in the patient group compared with the control group. The level of the 2H4+ subset did not differ between the two groups. No significant correlation was observed between the increase in the 4B4+ subset and disease severity, as estimated by measuring the proteinuria, levels of serum creatinine and immunoglobulins (Igs) or renal tissue damage. It was concluded that 4B4+ CD4+ and 4B4+ T alpha 4+ subsets might be involved in the mechanism of immunopathogenesis of IgA nephropathy.

Adult↗

[Surgical treatment of brain stem lesions with reference to cavernous angioma].

The surgical indications for localized brain stem lesions were evaluated retrospectively through the clinical results of 14 patients: 5 cavernous angiomas and 9 gliomas. Cavernous angiomas were located in fourth ventricle floor (2 cases), in dorsal midbrain (1 case), in right cerebellar peduncle (1 case), and in medulla oblongata (1 case). Those cases had direct surgery because of relapse of clinical symptoms and enlargement of the lesions on follow-up MR imagings. Each lesion was extirpated totally. Consequently, the majority of neurological deficits before operation improved. Therefore, radical extirpation in brain stem cavernous angioma was strongly recommended. Also, total, subtotal resection was performed for gliomas localized in brain stem: 2 low grade astrocytomas, 3 malignant astrocytomas, 3 plexus papillomas, and 1 ependymoma. Most of cases improved without new neurological deficits after surgery. In addition, MR imaging was considered to be essential to accurate diagnosis and surgical strategies for brain stem lesions.

Adolescent↗

Intraocular penetration and effect on the retina of fluconazole.

The intraocular concentration of fluconazole was measured in nonvitrectomized and vitrectomized eyes after an intravenous administration of 5 or 25 mg/kg fluconazole in albino rabbits. Respective fluconazole concentrations in the aqueous, vitreous and serum 1 hour after administration were 2.87, 1.72 and 4.60 micrograms/ml at 5 mg/kg administration, and 14.93, 7.05 and 20.63 micrograms/ml at 25 mg/kg administration, indicating high and dose-dependent intraocular penetration of fluconazole. Intraocular penetration of intravenously administered fluconazole was moderately, not very much, enhanced by vitrectomy. The in-vitro electroretinogram (ERG) remained unchanged after perfusion with 20 micrograms/ml of fluconazole. The in-vivo ERG and the visual evoked potential was unchanged after the daily administration of 25 mg/kg fluconazole for 8 days. The toxicity of fluconazole on the retina would be low and within safety limits so far as it is used at clinical dosage. Fluconazole may have a place in the treatment of fungal ocular infections.

Animals↗

[Changes of the insulin and glucagon receptors in bile-duct ligated rats].

The specific bindings of insulin and glucagon to 40000g pellets including hepatic plasma membrane were measured at 1, 2 or 4 weeks after bile-duct ligation or sham operation in rats. At 1 week after operation, insulin bindings were similar in both bile-duct ligated and control rats, however, glucagon binding in bile-duct ligated rats (30.1 +/- 5.99%) was significantly (p less than 0.01) lower than that in control rats (42.8 +/- 8.13%). At 2 and 4 weeks after operation, insulin bindings in bile-duct ligated rats (2 weeks: 35.2 +/- 3.32%, 4 weeks: 32.3 +/- 4.62%) were significantly (p less than 0.05) lower than those in control rats (2 weeks: 39.7 +/- 5.12%, 4 weeks: 38.4 +/- 3.85%). Therefore, glucagon bindings in bile-duct ligated rats (2 weeks: 26.3 +/- 4.32%, 4 weeks: 26.9 +/- 4.06%) were significantly (p less than 0.01) lower than those in control rats (2 weeks: 42.0 +/- 3.95%, 4 weeks: 45.3 +/- 4.29%). Decrease of insulin bindings, however, was less than that of glucagon bindings. Changes of the insulin and glucagon receptors on the hepatic plasma membrane suggested a reason for a disturbance of carbohydrate metabolism in the liver cell with obstructive jaundice.

Animals↗

[Clinical significance of serum carcinoembryonic antigen in small cell lung cancer patients].

In this study, the clinical significance of serum carcinoembryonic antigen (CEA) level in small cell lung cancer patients was investigated. The relationship between serum CEA level before treatment and the effect of chemotherapy was analyzed. In 97 evaluable patients with small cell lung cancer, the 26 who had elevated CEA values of 10.0 ng/ml or greater at diagnosis tended to be resistant to intravenous systemic chemotherapy. In patients with limited disease (LD), survival time of 13 patients whose CEA levels were 10.0 ng/ml or greater was shorter than that of the other LD patients. These findings suggest that small cell lung cancer patients with high serum CEA levels are less responsive to standard chemotherapy, and serum CEA level may be able to identify biologically different tumors from common small cell cancer.

Adult↗

Aortic valve replacement for Takayasu's arteritis.

We report 12 cases of aortic valve replacement performed for Takayasu's arteritis and discuss the genesis of aortic regurgitation and the clinical outcome after aortic valve replacement. This group of twelve patients who underwent aortic valve replacement between April 1982 and March 1990 included four male and eight female patients, aged 24 to 67 years (mean age 48 years). Preoperative angiography showed systemic multiple stenoocclusive or aneurysmal dilated vascular lesions in addition to aortic regurgitation. The multiple lesions included a lesion in the aortic arch branch in nine (75%), in the pulmonary artery in seven (58%), an aneurysmal dilation in the ascending aorta of more than 6 cm in four (33%), a coronary lesion in four (33%), a thoracic aortic lesion in six (50%), and a lesion in the abdominal aorta and its visceral branch in six (50%). Simple aortic valve replacement alone was performed in two patients and in combination with another operation in ten patients, with aortic root reconstruction in two, ascending aortic plication in three, coronary artery bypass grafting in two, aortic arch branch bypass grafting in one, aortic arch branch bypass grafting and coronary ostium endarterectomy in one, and mitral valve replacement and ascending aortic plication in one. There was no operative death, and only one patient died later, 18 months after the operation, because of secondary amyloidosis. The postoperative recovery of the clinical status and cardiac function was good. Intraoperative observations suggested that aortic valve regurgitation may be caused by an extension of aortitis, although histopathologic examinations of the valve showed nonspecific findings. One of the characteristic problems in Takayasu's arteritis is the necessity for prednisolone administration in some patients preoperatively or postoperatively, or both. We conclude that aortic valve replacement for patients with Takayasu's arteritis is an effective and safe treatment. Our data related to the genesis of aortic regurgitation in Takayasu's arteritis remain insufficient to draw conclusions, and further analysis is planned.

Aortic Valve↗

Suppression of hepatic drug metabolism by the interferon inducer, polyriboinosinic acid:polyribocitidylic acid.

Since the discovery that interferon inducers depress hepatic drug metabolism, the depressant action of cytochrome P450 (P450) has been demonstrated to be shared by cytokines such as interferon alpha/beta and interferon gamma as well as interleukin-1 and tumor necrosis factor. Because these cytokines are inflammatory mediators, it is not surprising that theophylline toxicity has been reported in patients with influenza B epidemic. Hence, to lay a foundation for studies of altered steroid and drug metabolism, the alteration of P450 isozymes was studied after polyriboinosinic acid:polyribocitidylic acid (poly I:poly C) administration. Twenty-four hours after poly I:poly C administration, hepatic P450 content decreased to 57% of control, whereas depression of other microsomal enzymes was less pronounced: P450 reductase (69%), cytochrome b5 (74%) and NADH-cytochrome b5 reductase (85%). The depression of mRNA for cytochrome P450 1A1, 1A2, 2C11 and 2E1 was more than 60% of the controls. Recovery of mRNA levels was not complete within 72 hr. The changes in mRNAs, in general, paralleled alterations of monooxygenase activities and P450 isozyme content suggesting that the effect of poly I:poly C is pretranslational for all P450 isozymes studied. No overt differential effect on P450 isozymes was found after an administration of poly I:poly C. This study complements the previous report which demonstrated down-regulation of mRNA for cytochrome P450 2C11 and 3A2.

Animals↗