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Biomedical subjects

H Kuno

Publications and source records attributed to H Kuno.

At least 37 records · Page 2Linked to original sources

Vitamin D status and nonhemiplegic bone mass in patients following stroke.

To assess bone changes in hemiplegic stroke patients, vitamin D status and bone density on hemiplegic and intact sides of sunlight deprived stroke patients were evaluated. Sera were collected from 88 hemiplegic stroke patients and 34 controls. The sera were assayed for 25-hydroxyvitamin D (25-OHD) and 1, 25 dihydroxyvitamin D (1, 25-[OH]2D). Bone density was measured bilaterally from radiographs of the hands using computed X-ray densitometry (CXD) and the Z-score of bone mineral density was calculated. Serum 25-OHD and 1, 25-[OH]2D concentrations were significantly lower in patients (11.5 +/- 5.4 ng/mL, 23.1 +/- 10.3 pg/mL) than in controls (21.6 +/- 3.1 ng/mL, 49.6 +/- 9.2 pg/mL) (P < .0001). The patients' Z-scores for osteopenia were lower on the hemiplegic side than on the nonhemiplegic side. Even on the intact side, the Z-scores were significantly lower as compared to controls. In addition to the strong positive correlation between the Z-scores on the hemiplegic side and degree of hemiplegia, the Z-scores on both sides in patients correlated positively with the serum 25-OHD concentration. These results suggest that vitamin D deficiency and disuse can cause osteopenia on the hemiplegic side and may increase the risk of hip fracture. In addition, it was demonstrated that hypovitaminosis D decreased bone mass on the nonhemiplegic side. This hypovitaminosis D might be corrected readily by the routine use of vitamin D supplements.

Adult↗

[Results of cataract surgery in patients with uveitis].

PURPOSE: Extraction of cataracts with posterior chamber intraocular lens (PC-IOL) implantation has been attempted with some encouraging results in uveitis having minor intensity. However, the number of operated patients is very limited. We present the results in patients having more important intensity of uveitis. MATERIALS AND METHODS: The authors studied 28 eyes in 20 patients who underwent cataract extraction as a complication of uveitis. RESULTS: All the operations were accomplished by phacoemulsification and aspiration (PER) with posterior chamber lens implanted in 23 eyes. Etiologic diagnosis included 8 sarcoidosis, 5 Behçet, 3 Vogt-Koyanagi-Harada syndrome and 12 other aetiologies. Eighty percent of patients obtained visual acuity better than 0.6 postoperatively. Postoperative complications were not severe. CONCLUSIONS: The indication of PC-IOL could be given to cataracts in chronic uveitis if the patients are older than 35 years and there are no uveal inflammatory signs at least 3 months prior to considered implantation.

Adult↗

Alcoholysis of epsilon-decalactone with polyethylene glycol-modified lipase in 1,1,1-trichloroethane.

Lipase from Pseudomonas cepacia was modified with 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine, activated PEG2, to form PEG-lipase. The PEG-lipase is soluble and active in organic solvents. It catalyzes alcoholysis of racemic epsilon-decalactone with ethanol in 1,1,1-trichloroethane to form (R)-hydroxydecanoic acid ethyl ester. No alcoholysis of (S)-decalactone takes place. These results were discussed in relation to carbon number of n-alcohol, optimum temperature and comparison with modified and non-modified lipases.

Ethylene Glycols↗

A single up-stream element confers responsiveness to 1,25-dihydroxyvitamin D3 and tumor necrosis factor-alpha in the rat osteocalcin gene.

Tumor necrosis factor-alpha (TNF alpha) is one of several autocrine/paracrine factors known to exert potent inhibitory effects on bone. We have shown that TNF alpha inhibition of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-stimulated synthesis of the bone-specific protein osteocalcin (OC) occurs by decreasing steady state levels of OC mRNA, suggesting a pretranslational mechanism. In many genes, TNF alpha action is mediated by the transcription factor NF kappa B. Analysis of OC 5'-flanking DNA revealed a sequence structurally homologous to the previously described NF kappa B-binding site and, thus, a potential TNF alpha response element. Deletion analysis was performed to identify the sequences mediating the response to TNF alpha in osteoblastic ROS 17/2.8 cells by transient transfection with reporter constructs containing rat OC 5'-flanking DNA [chloramphenicol acetyltransferase (CAT)] that retained or deleted homologous NF kappa B sites or a previously defined 1,25-(OH)2D3 response element (VDRE). Transfection with all reporter constructs resulted in low basal CAT activity, measured 72 h after transfection. 1,25-(OH)2D3 stimulated CAT activity 2.8- to 4.5-fold in cells transfected with constructs that included the VDRE. TNF alpha inhibited 1,25-(OH)2D3-stimulated, but not basal, CAT activity. Deletion analysis localized the effect of TNF alpha to a sequence between -522 and -306 relative to the OC transcription start site, an area that included the VDRE but deleted a homologous NF kappa B element. Transfection of cells with a heterologous reporter containing one copy of the OC VDRE inserted in correct orientation or two copies in inverse orientation was sufficient to confer a response to TNF alpha. Gel mobility shift analysis of DNA-nuclear protein interaction revealed that 1,25-(OH)2D3 stimulated an increase in binding of nuclear proteins to an OC 32P-VDRE probe. Preincubation of nuclear extract with specific monoclonal antibodies confirmed that the proteins binding the VDRE included the vitamin D receptor and retinoid-X receptor. TNF alpha treatment of cells inhibited the 1,25-(OH)2D3-stimulated increase in nuclear protein binding to the VDRE. These results suggest 1) the VDRE is sufficient to confer a response to the inhibitory effect of TNF alpha on 1,25-(OH)2D3-stimulated rat OC gene transcription; 2) the action of TNF alpha does not require homologous NF kappa B response elements; and 3) the mechanism of TNF alpha inhibition of 1,25-(OH)2D3-stimulated OC gene expression includes modulation of binding of the vitamin D receptor/retinoid-X receptor heterodimer to the VDRE.

Animals↗

Inhibition of 1,25-dihydroxyvitamin D3 stimulated osteocalcin gene transcription by tumor necrosis factor-alpha: structural determinants within the vitamin D response element.

Control of osteoblast function requires the coordinate activity of systemic and local regulatory factors. We have investigated the mechanism of interaction between the secosteroid 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and the cytokine tumor necrosis factor-alpha (TNF-alpha) by measuring their effects on two 1,25-(OH)2D3 responsive matrix protein genes, osteocalcin (OC) and osteopontin (OP). Our previous studies revealed that an inhibitory effect of TNF-alpha on 1,25-(OH)2D3-stimulated OC gene transcription is conferred by the same 25 base pair region of 5'-flanking DNA that confers a response to vitamin D (VDRE). Gel mobility shift studies of [32P]VDRE binding to ROS 17/2.8 cell nuclear extract revealed that TNF-alpha inhibits 1,25-(OH)2D3 stimulated formation of specific retinoid X receptor/vitamin D receptor (RXR/VDR)-DNA complexes in vitro. To determine if TNF-alpha was inhibiting nuclear protein-VDRE binding by modulation of VDR availability, we measured intranuclear VDR in cells treated with 1,25-(OH)2D3 (10(-8) M), TNF-alpha (100 ng/ml), or both, by western blot. 1,25-(OH)2D3 caused upregulation of the nuclear VDR. Treatment with TNF-alpha inhibited the 1,25-(OH)2D3-stimulated up-regulation of VDR nuclear protein content. However, down-regulation of VDR was unlikely to be the mechanism of TNF-alpha action because TNF-alpha had no effect on 1,25-(OH)2D3 stimulation of steady state OP messenger RNA or transcription of an OP-VDRE-chloramphenicol acetyl transferase reporter construct. These results suggest that decreased VDR alone does not explain the mechanism of TNF-alpha action. VDRE structural requirements for TNF-alpha action were characterized by comparing binding of mutant and hybrid forms of mouse (m)OP-, rat (r)OC-, and human (h)OC-VDRE probes to nuclear protein from cells treated with 1,25-(OH)2D3 and/or TNF-alpha. These homologous vitamin D response elements differ in that an AP-1 sequence is included in the rOC-VDRE and hOC-VDRE but not in the OP-VDRE. Gel mobility shift analysis revealed that TNF-alpha inhibited 1,25-(OH)2D3 stimulation of nuclear protein binding to rOC-VDRE and hOC-VDRE to 59% and 69% of control, respectively, but had no effect on 1,25-(OH)2D3 stimulation of nuclear protein binding to OP-VDRE. The effect of TNF-alpha could not be conferred in a mutant OP-VDRE in which the rOC-VDRE AP-1 sequence was inserted.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗

Critical period for induction of ocular anomalies produced by soft x-ray irradiation (4.6 Gy) in the rat F1 offspring.

A minimal dose of soft x-ray irradiation of 4.6 Gy is expected to produce ocular anomalies on gestational day 9. A study was performed to determine whether ocular anomalies are induced in rat F1 offspring at this dose level on gestational days 6, 7, 8, 9, 10, and 11. Eyes were examined during postnatal week 5 using indirect ophthalmoscopy and biomicroscopy. Anophthalmia (1.3% and 12.1%), microphthalmia (3.8% and 6.9%), iris coloboma (3.8% and 6.9%) and choroidal coloboma (2.5% and 8.6%) were observed in the gestational day 8 and 9 treatment groups, respectively. There were no treatment-related ophthalmological abnormalities at the other time points. It is concluded that the most sensitive period for induction of ocular anomalies by soft x-ray irradiation at a dose of 4.6 Gy under these experimental conditions is during gestational days 8 and 9, and that gestational day 9 appears to be more sensitive than day 8.

Animals↗

Formation of transitivity in conditional matching to sample by pigeons.

Four homing pigeons were trained over 5 months in a zero-delay, "arbitrary" matching-to-sample procedure with sample and comparison stimuli presented on any of three response keys. Birds were also required to complete a fixed-ratio 10 requirement on both sample and comparison stimuli to terminate their presentation. The procedure resulted in the establishment of relations that were not specifically trained and that can be characterized by the property of transitivity in a stimulus equivalence context. This result was in contrast with the findings obtained from most previous research with nonhuman subjects.

Journal Article↗

Cytokines affecting survival and differentiation of an astrocyte progenitor cell line.

The effects of various cytokines on survival and differentiation of an astrocyte progenitor cell line (AP-16) were examined. Epidermal growth factor (EGF) deprivation caused death of AP-16 cells by apoptosis. Transforming growth factor-alpha (TGF-alpha) and basic fibroblast growth factor (bFGF) prevented the apoptosis occurring in the absence of EGF. Leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) induced glial fibrillary acidic protein (GFAP) and decreased A2B5 antigen in AP-16 cells, indicating that these cytokines induced AP-16 cells to differentiate into astrocytes.

Animals↗

Effects of soft X-ray irradiation on ocular development in Sprague-Dawley rats.

Pregnant rats were irradiated with soft x-rays at a dose of 1.6, 3.2, 6.3 or 12.6 Gy on Day 9 of gestation, and the eyes of F1 offspring were examined using indirect ophthalmoscopy and biomicroscopy during Postnatal Week 5. Ophthalmoscopic examination revealed iris and choroidal coloboma, microphthalmia and anophthalmia in the 3.2, 6.3 and 12.6 Gy groups. In addition to those anomalies, lens luxation and associated anterior displacement of the vitreous face, and retinal vascular anomalies were observed in the 12.6 Gy group. Histological examination revealed agenesis of retinal vessels. Ophthalmoscopic examination using biomicroscopy and indirect ophthalmoscopy detected choroidal coloboma, lens and vitreous luxation and defect in retinal vessels which could not be detected by external observation, demonstrating the usefulness of this technique in the postnatal stage of teratology studies.

Animals↗

Usefulness of ophthalmic examination in postnatal observation in teratology studies.

Pregnant rats were irradiated with soft x-ray at a dose of 635 r or 1270 r on Day 9 or 11 of gestation. The eyes of F1 offspring were examined by indirect ophthalmoscopy and slit lamp biomicroscopy in postnatal weeks 3 to 7. Ophthalmoscopic examination of offspring irradiated at a dose of 635r or 1270r on Gestational Day 9 revealed iris and choroidal coloboma together with microphthalmia and anophthalmia at Postnatal Week 3 or later. Choroidal coloboma, an anomaly that cannot be detected by the common external observation method, was found ophthalmoscopically in one rat without any external ocular abnormalities. This fact suggests that ophthalmoscopy in postnatal observation can be useful to detect ocular teratogenic potential of test compounds in preclinical safety studies.

Abnormalities, Radiation-Induced↗

Stratum corneum lipids serve as a bound-water modulator.

Stratum corneum lipids have been found to be an important determinant involved in the water-holding function of the stratum corneum. In order to further elucidate the significance of stratum corneum lipids in the water-holding properties, the hydration behavior of the stratum corneum following depletion and replenishment of the lipids has been studied, using an isolated human forearm stratum corneum sheet, by differential scanning calorimetry parallel to ultrastructural changes of intercellular lipids in the stratum corneum. Extraction of the stratum corneum sheet with acetone/ether (1/1) decreased the bound-water content from 33.3% to 19.7%, where the melting temperature of ice remained constant. Further extraction with water, which released a large amount of water-soluble materials such as amino acids, did not change the bound-water content, but definitely raised the melting temperature of ice. The application of the stratum corneum lipids, which were solubilized in squalane containing 1% alpha-monomethyl heptadecyl glyceryl ether to the lipid-depleted stratum corneum sheet, caused a significant recovery of bound-water content to the previous, almost normal level. In accordance with the hydration behavior, electron microscopic analysis of the acetone/ether-treated stratum corneum sheet revealed selective depletion of lipids from the intercellular spaces, accompanied by a marked disruption of multiple lamellar structures. In contrast, the application of stratum corneum lipids into the lipid-depleted stratum corneum sheet resulted in the restoration of the lamellar structure between the stratum corneum cells. These findings strongly suggest that stratum corneum lipids serve a water-holding function through the formation of lamellar structures within the stratum corneum.

Adult↗

Spontaneous ophthalmic lesions in young Sprague-Dawley rats.

Eight hundred eight Sprague-Dawley rats were examined for ophthalmic abnormalities during a pretest period in various preclinical safety assessment studies. Persistent pupillary membrane, corneal crystal, healed minor trauma, synechia, coloboma of the iris, lens luxation, cataract, persistent hyperplastic primary vitreous, vitreous hemorrhage, coloboma of the optic disc or choroid, remnant of hyaloid arterial system, retinal hemorrhage, retinal detachment, retinal folding and choroidal defect were observed. The incidences of corneal crystal, synechia, and nuclear cataract in this survey were higher than those reported previously. On the other hand, retinal folding in this survey was less common than that reported previously. These results suggest that background data of eye problems in albino rats should be accumulated in each own laboratory colony. In addition, since spontaneous eye problems are common in young albino rats, elimination of rats with ophthalmic abnormalities from study groups by an ophthalmic examination during a pretest period would facilitate to evaluate toxicity potential of test compounds in safety assessment studies.

Animals↗

Effects of water temperature and weight of wheel load on water wheel turning behavior of imipramine administered mice.

This experiment investigated the effect of imipramine on water wheel turning behavior in relation to the water temperature and the wheel load. It was shown that the higher the water temperature, the more the mice rotated the wheel, and the greater the wheel load, the less mice rotated it. However, these factors did not reduce the effect of imipramine, which increased the number of responses. It was suggested that the water wheel test shows promise as a screening test for antidepressants.

Animals↗

[Decreased beta-adrenergic receptor binding in the rat's brain on the activity-stress paradigm].

It was recently suggested that beta-adrenergic receptor binding in the rat brain was decreased by repeated electric shocks. In order to examine whether this phenomenon is observed under another stressor, the activity-stress paradigm was used in the present study. Rats were divided into 3 groups of AS, DC and AC.AS was housed in a cage with a running wheel and fed 1 hour daily. DC was fed in the same condition as AS, but housed in a cage without the wheel. AC was housed in a running wheel cage and fed in standard condition. AS exhibited excessive running and subsequently revealed sharp reduction of activity, body weight and food consumption on 7 or 8th experimental day. When these decrement was seen in AS, each rat was decapitated and beta-receptor binding was measured. AS showed excessive stomach ulcers, but DC and AC didn't. beta-Receptor binding in the cerebral cortex of AS was significantly lower than that of other groups. These results indicate that beta-receptor binding in the rat cortex was also decreased by the activity-stress paradigm.

Animals↗