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Biomedical subjects

K Hanada

Publications and source records attributed to K Hanada.

At least 217 records · Page 12Linked to original sources
PubMed1994

Stimulation of fracture repair by recombinant human basic fibroblast growth factor in normal and streptozotocin-diabetic rats.

The effect of local application of recombinant human basic fibroblast growth factor (rhbFGF) on fracture repair was examined using normal rats and streptozotocin-diabetic rats with impaired repairing ability. Immediately after fracturing the fibula, rhbFGF was applied by a single injection to the fracture site. Application of rhbFGF increased the volume and mineral content of callus in a dose-dependent manner in both normal and diabetic rats, and callus formation of diabetic rats was stimulated to levels similar to those in nontreated normal rats. The marked effect of rhbFGF on fracture repair was associated with an improvement in the mechanical properties of the healing fibula in both normal and diabetic rats. Immunohistochemical staining showed that endogenous bFGF was widely distributed in normal rats 1 and 3 weeks after fracture, especially in the soft callus and periosteum, whereas much less bFGF was detected in diabetic rats. Insulin treatment of diabetic rats restored the immunostaining for bFGF. These results demonstrate that bFGF is expressed during the early stage of fracture repair, and that the impaired fracture-repairing ability in diabetic rats is associated with reduced expression of bFGF at the fracture site. A single application of bFGF immediately after fracture not only facilitates the repair process in normal rats, but also recovers the impaired repairing ability in diabetic rats. These results suggest that local application of bFGF may facilitate bone union in patients with impaired as well as normal repairing ability.

Animals↗
PubMed1994

Isolation and characterization of new 18-membered macrolides FD-891 and FD-892.

New 18-membered macrolides FD-891 and FD-892 were discovered from the fermentation broth of Streptomyces graminofaciens A-8890 isolated from a soil sample collected at Yamanashi prefecture Japan. They induce morphological changes of HL-60 cells at low concentration below IC50s and have cytocidal activity against in vitro tumor cell lines. FD-891 showed 2 approximately 7 times stronger activity than doxorubicin whereas FD-892 was 20 approximately 100 fold weaker than FD-891 and doxorubicin.

Adenosine Triphosphatases↗
PubMed1994

Isolation and characterization of a new 12-membered macrolide FD-895.

During the course of our screening program for natural product drugs effective against multidrug resistant cells by using adriamycin resistant HL-60 cells, we have discovered a new 12 membered macrolide FD-895 in the fermentation broth of Streptomyces hygroscopicus A-9561 isolated from a soil sample collected at Iriomote Island, Okinawa prefecture, Japan. FD-895 showed stronger cytocidal activities against in vitro tumor cell lines than adriamycin. FD-895 had the same IC50 values against parent and adriamycin resistant HL-60 cells.

Anti-Bacterial Agents↗
PubMed1993

Sphingolipid deficiency induces hypersensitivity of CD14, a glycosyl phosphatidylinositol-anchored protein, to phosphatidylinositol-specific phospholipase C.

Strain SPB-1 is a temperature-sensitive Chinese hamster ovary cell mutant defective in sphingoid base biosynthesis. To examine the effects of sphingolipid deficiency on a glycosyl phosphatidylinositol-anchored protein, we constructed transfectants expressing mouse CD14 from the SPB-1 and the wild type cells. When the cells were precultured in a sphingolipid-deficient medium at 39 degrees C, CD14 expressed in the SPB-1 cells was hypersensitive to phosphatidylinositol-specific phospholipase C (PI-PLC), compared with that in the wild type cells. Moreover, after exposure of the cells to fumonisin B1, an inhibitor of ceramide synthase, CD14, even in the wild type cells, became hypersensitive to PI-PLC. The PI-PLC hypersensitivity in the SPB-1 cells was almost completely suppressed when the cells were cultured in the presence of exogenous sphingosine or sphingomyelin. On the other hand, the hypersensitivity induced by fumonisin B1 was suppressed by exogenous sphingomyelin but not by sphingosine. The suppression by exogenous glucosylceramide was partial under both conditions. Likewise, CD14 molecules in membranes prepared from the sphingolipid-deficient cells were more sensitive to PI-PLC than those from the control cells. These results indicated that a deficiency in cellular complex sphingolipids caused the PI-PLC hypersensitivity of CD14, suggesting the interaction of CD14 with sphingolipids in membranes.

Animals↗
PubMed1993

Alteration of nerve growth factor-receptor expression in the periodontal ligament of the rat during experimental tooth movement.

This pilot study deals with the initial responses of neural elements showing nerve growth factor-receptor (NGFR) immunoreactivity in the periodontal ligament of rats to orthodontic forces. The animals were killed at intervals of 1, 2, 6, 12 h and 1, 3, 5, 7 days after the insertion of elastic bands between the maxillary first and second molars. Serial frozen sections, prepared from each animal, were processed immunohistochemically to demonstrate NGFR, after which the periodontal ligament of the mesial root of the maxillary second molar was examined microscopically. In control sections, NGFR-positive neural elements were predominantly distributed at the apex of the bony socket on the distal side of the periodontal ligament. After 1 h of tooth movement, NGFR positively-stained nerve fibres tended to disappear slightly in both the intermediate and coronal regions of the distal periodontal ligament. By the third day of tooth movement, the periodontal ligament nerve fibres showed more intense NGFR-immunoreactivity; thick, positively stained nerve fibres were recognized on the distal side in which active bone remodelling was occurring, and a few of these fibres were densely distributed around blood vessels or near Howship's lacunae. The distribution of NGFR-positive neural elements on the mesial side increased at 5 days of tooth movement. Finally, at 7 days of tooth movement, staining intensity for NGFR appeared to decrease. These findings demonstrate that an alteration in the distribution and the intensity of immunoreactive staining for NGFR in the periodontal ligament is associated with the bone remodelling induced by orthodontic tooth movement.

Animals↗
PubMed1993

Masticatory function in patients with mandibular prognathism before and after orthognathic surgery.

Masticatory function was analyzed in 54 patients with mandibular prognathism before or after orthognathic treatment and in 40 adults with normal occlusion. Masticatory efficiency was evaluated spectrophotometrically by measuring the amount of adenosine triphosphate eluted from masticated adenosine triphosphate granules. Occlusal contact was evaluated by calculating the number and area of occlusal contacts from the illuminated images of a silicone record of the occlusion that was stored in the image analysis system with the aid of a charge-coupled device camera. The mean masticatory efficiency of the preoperative group was approximately half that of the control group. The value for the postoperative group was slightly higher than that for the preoperative group, but there was no statistical difference between the two groups. Likewise, the number and area of occlusal contacts in the preoperative group were also approximately half or less as compared with those of the control group, and they did not show significant changes postoperatively. Statistically, there were correlations between the masticatory efficiency and the number and area of occlusal contacts. The results indicate that although the occlusal relationship of the upper and lower teeth were greatly improved by orthognathic treatment, the postoperative occlusion is not tight enough and may need further adjustment at the end of the treatment.

Adenosine Triphosphate↗
PubMed1993

The effects of surgical-orthodontic correction of skeletal class III malocclusion on mandibular movement.

The effects of surgical-orthodontic treatment on mandibular movement were studied using the mandibular kinesiograph in 30 patients with skeletal class III malocclusion that was corrected by the sagittal split osteotomy (27 patients), a combination of the sagittal split osteotomy and body ostectomy (2 patients), or the sagittal split osteotomy and a posterior alveolar osteotomy of the maxilla (1 patient). Postoperatively, the mean maximum anterior and posterior excursions of the mandible increased significantly from 4.1 to 6.7 mm and from 0.6 to 2.6 mm, respectively. The lateral excursion to the right and left sides also showed significant increases from 4.8 to 7 mm and from 5.5 to 7 mm, respectively, after surgery. In analysis of the habitual and rapid opening and closing movements of the mandible, marked impairment was not observed in most patients except for crossing and discrepancy in the tracings of the habitual opening and closing movements in the sagittal plane observed in 11 patients. These findings were observed in only one patient postoperatively. The results indicate that the surgical orthodontic correction of skeletal class III malocclusion has favorable effects on the function of the mandible.

Adolescent↗
PubMed1993

Analyses of serum copper and zinc levels and copper/zinc ratios in skin diseases.

With the objective of comprehending abnormal metabolisms of the essential metals of zinc (Zn) and copper (Cu) in three groups of skin diseases, skin cancer, inflammatory diseases, and non-inflammatory disease, we measured serum levels of Zn and Cu in 151 cases of various cutaneous manifestations and estimated the significance of the ratios between the two metals (Cu/Zn). The serum level of Zn was significantly decreased in cases of bullous pemphigoid, decubitus ulcer, and alopecia areata. The serum level of Cu was elevated in cases of psoriasis, decubitus ulcer, and skin cancer. We observed no elevation of serum Zn level or abnormally depressed serum Cu level. The Cu/Zn ratio showed significantly different values among these three groups of the diseases, suggesting the utility of measuring Cu/Zn ratios for differential diagnosis over that of determining the serum level of Zn or Cu alone. It was also demonstrated that, in each skin disease, the Cu/Zn ratio clearly reflects the severity of the progress.

Adult↗
PubMed1993

Microbial hydroxylation of (-)-eburnamonine by Mucor circinelloides and Streptomyces violens.

(6R)-6-Hydroxy-, (6S)-6-hydroxy- and (18S)-18-hydroxyeburnamonines were obtained by microbial conversion of (-)-eburnamonine using Mucor circinelloides and Streptomyces violens. Their structures were determined by analyses of the mass, 1H- and 13C-NMR spectra. (-)-Eburnamonine and the three hydroxylated compounds showed cerebral protecting effects against potassium cyanide intoxication in mice.

Animals↗
PubMed1993

Chin augmentation with porous hydroxyapatite blocks.

The results of chin augmentation by porous hydroxyapatite blocks were evaluated clinically and radiographically in nine patients. Recovery of a satisfactory facial profile was achieved by the procedure, and all patients but one, with removal of the implant because of infection, were satisfied with the results of the surgery. Radiographically, the implants were incorporated into the bony structure of the mandible by deposition of bone at and around the bone-implant interface and ingrowth of bone into pores. Cephalometrically, the procedure was found to provide very stable results, with little change in the position of the implants and no appreciable resorption of the implants and bone. Despite heavy chemotherapy, histologic examination of the removed hydroxyapatite showed the presence of areas with numerous inflammatory cell infiltration and no bone formation. Thus, the procedure is quite useful for chin augmentation, but utmost care should be taken to avoid infection.

Adolescent↗
PubMed1992

Sphingolipids are essential for the growth of Chinese hamster ovary cells. Restoration of the growth of a mutant defective in sphingoid base biosynthesis by exogenous sphingolipids.

We previously isolated a temperature-sensitive Chinese hamster ovary cell mutant (strain SPB-1) with thermolabile serine palmitoyltransferase, which is involved in the first step of sphingolipid synthesis (Hanada, K., Nishijima, M., and Akamatsu, Y. (1990) J. Biol. Chem. 265, 22137-22142). In this study, sphingolipid-deficient culture medium was used to examine the effect of exogenous sphingolipids on the cell growth of SPB-1. When cultivated in the sphingolipid-deficient medium, SPB-1 cells ceased growing at non-permissive temperatures. Under these conditions, de novo sphingolipid synthesis ceased in the SPB-1 cells, resulting in a decrease in levels of sphingomyelin and ganglioside sialyl lactosylceramide (GM3), whereas the parental CHO-K1 cells grew logarithmically with normal sphingolipid synthesis. Exogenous sphingosine restored the contents of both sphingomyelin and GM3 in the SPB-1 cells near to the parental levels through metabolic utilization and allowed the mutant cells to grow even at the non-permissive temperature. Similarly, exogenous sphingomyelin restored the sphingomyelin levels and only partly the GM3 levels and also suppressed the temperature-sensitivity of the SPB-1 cell growth. In contrast, exogenous glucosylceramide, which restored the GM3 levels but not the sphingomyelin levels, failed to suppress the temperature sensitivity of the SPB-1 cell growth. Combination of exogenous sphingomyelin with ceramide, glucosylceramide, GM3, or sphingoid bases did not show any synergistic or additive effect on the SPB-1 cell growth enhancement, compared with sphingomyelin alone. The results indicated that the temperature sensitivity of the SPB-1 cell growth was due to the lack of cellular sphingolipids, possibly that of sphingomyelin.

Acyltransferases↗
PubMed1992

Sodium ion and proline binding sites in the Na+/proline symport carrier of Escherichia coli.

Proline binding activity of the Escherichia coli Na+/proline symport carrier is inhibited by a sulfhydryl reagent, N-ethylmaleimide (NEM). Proline and its analogs protected the carrier against the NEM-inactivation in a Na+ (or Li+)-dependent manner. Na+ alone, even in the absence of proline, partially protected it from the NEM-inactivation. Mutant proline carriers, CS281, CS344 and CS349, which have a serine residue in place of Cys-281, Cys-344 and Cys-349, respectively (Yamato, I. and Anraku, Y. (1988) J. Biol. Chem. 263, 16055-16057) were also analyzed for cation-dependent proline binding and NEM-sensitivity. Proline binding activities of CS281 and CS344 were almost completely resistant to NEM, whereas that of CS349 was not. Furthermore, the proline binding activity of CS344 was remarkably lower than those of the wild-type, CS281 and CS349 carriers. These results indicate that Cys-344, which is located in the putative eighth membrane-spanning domain in the carrier, is a cysteine residue functionally involved in the high-affinity binding for sodium ion and proline.

Amino Acid Sequence↗
PubMed1992

Neuroendocrine aspects of primary endogenous depression. XI. Serum melatonin measures in patients and matched control subjects.

To ascertain the extent of dysregulation of melatonin secretion in endogenous depression, we measured nocturnal and diurnal serum melatonin concentrations in 38 depressed patients (23 women and 15 men) who had primary, definite endogenous depression according to the Research Diagnostic Criteria and in 38 individually matched normal control subjects. Previous reports have suggested that such patients may have reduced nocturnal melatonin secretion, often in conjunction with increased hypothalamic-pituitary-adrenal cortical axis activity. This has been considered as a possible reflection of reduced noradrenergic activity in depression. Compared with their matched controls, the depressed patients showed a trend toward a significantly elevated average nocturnal melatonin concentration that was accounted for primarily by the 14 premenopausal women--the postmenopausal female and male depressive patients did not differ significantly from their respective controls. The average diurnal melatonin concentration also showed a trend toward being higher in both the female and male depressed patients. The melatonin measures were not consistently related to any of the previously reported hypothalamic-pituitary-adrenal cortical axis measures in these subjects. Our findings thus failed to confirm a "low melatonin syndrome" or an inverse relationship between nocturnal melatonin and nocturnal cortisol concentrations in depression. This discrepancy may be related to methodologic differences among studies; our data are in accord with those findings of the one other reported study in which normal controls were individually matched to patients on variables that were known to influence melatonin secretion. Most of the studies, including ours, have been cross-sectional.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Mouse rRNA gene transcription factor mUBF requires both HMG-box1 and an acidic tail for nucleolar accumulation: molecular analysis of the nucleolar targeting mechanism.

RNA polymerase I requires at least two nucleolar transcription factors, UBF and SL-1, for ribosomal RNA gene (rDNA) transcription. UBF requires SL-1 for the formation of a stable initiation complex on the rDNA promoter region. We have determined the region of mouse UBF (mUBF) required for nucleolar targeting. Although mUBF has a nuclear localization sequence, this sequence alone is not sufficient for mUBF to accumulate in the nucleolus. Deletion analyses show that mUBF requires a wide region except for the N-terminal 101 amino acids for nucleolar targeting. Deletion of either the HMG-box1, a region crucial for rDNA binding, or the acidic tail, a region that may interact with SL-1, results in the loss of nucleolar targeting. We show by DNA affinity analysis that the HMG-box1 is absolutely necessary for mUBF to bind to the upstream control element of the rDNA. We also show that mUBFs with various internal deletions retain both nucleolar targeting and DNA binding ability. A clear correlation was demonstrated between the DNA binding and nucleolar targeting ability. These results suggest that UBF is transferred to the nucleus by its NLS and is sequestered in the nucleolus by its specific and stable binding to the rDNA promoter via HMG-boxes and the acidic tail.

Animals↗
PubMed1992

Transformation of vitamin D3 to 1 alpha,25-dihydroxyvitamin D3 via 25-hydroxyvitamin D3 using Amycolata sp. strains.

To enzymatically synthesize active metabolites of vitamin D3, we screened about 500 bacterial strains and 450 fungal strains, of which 12 strains were able to convert vitamin D3 to 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] via 25-hydroxyvitamin D3 [25(OH)D3]. The conversion activity was only detected in strains belonging to the genus Amycolata among all the organisms tested. A preparative-scale conversion of vitamin D3 to 25(OH)D3 and 1 alpha,25(OH)2D3 in a 200-1 tank fermentor using A. autotrophica FERM BP-1573 was accomplished, yielding 8.3 mg 25(OH)D3/l culture and 0.17 mg 1 alpha,25(OH)2D3/l culture. A related compound, vitamin D2, could be also converted to 25-hydroxyvitamin D2 and 1 alpha,25-dihydroxyvitamin D2 using the same strain. The cytochrome P-450 of FERM BP-1573 was detected by reduced CO difference spectra in whole-cell suspensions. Vitamin D3 in the culture induced cytochrome P-450 and the conversion activity simultaneously, suggesting that the hydroxylation at C-25 of vitamin D3 and at C-1 of 25(OH)D3 originates from cytochrome P-450.

Actinomycetales↗