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Biomedical subjects

Y Higuchi

Publications and source records attributed to Y Higuchi.

At least 55 records · Page 3Linked to original sources
PubMed2000

Protective effect of aminoguanidine on hypoxic-ischemic brain damage and temporal profile of brain nitric oxide in neonatal rat.

Nitric oxide (NO) produced by inducible NO synthase contributes to ischemic brain damage. However, the role of inducible NO synthase-derived NO on neonatal hypoxic-ischemic encephalopathy has not been clarified. We demonstrate here that aminoguanidine, a relatively selective inhibitor of inducible NO synthase, ameliorated neonatal hypoxic-ischemic brain damage and that temporal profiles of NO correlated with the neuroprotective effect of aminoguanidine. Seven-day-old Wister rat pups were subjected to left carotid artery occlusion followed by 2.5 h of hypoxic exposure (8% oxygen). Infarct volumes (cortical and striatal) were assessed 72 h after the onset of hypoxia-ischemia by planimetric analysis of coronal brain slices stained with hematoxylin-eosin. Aminoguanidine (300 mg/kg i.p.), administered once before the onset of hypoxia-ischemia and then three times daily, significantly ameliorated infarct volume (89% reduction in the cerebral cortex and 90% in the striatum; p<0.001). NO metabolites were measured by means of chemiluminescence using an NO analyzer. In controls, there was a significant biphasic increase in NO metabolites in the ligated side at 1 h (during hypoxia) and at 72 h after the onset of hypoxia (p<0.05). Aminoguanidine did not suppress the first peak but significantly reduced the second one (p<0.05), and markedly reduced infarct size in a neonatal ischemic rat model. Suppression of NO production after reperfusion is a likely mechanism of this neuroprotection.

Animals↗
PubMed2000

1Alpha-hydroxyvitamin D3 prevents the decrease of bone mineral density in lactating beagles.

We assessed the change of bone mineral density (BMD) in lactating beagles with dual energy X-ray absorptiometry (DXA) and the preventive effect of 1alpha-hydroxyvitamin D3 (1alpha(OH)D3) on the BMD. Beagles, two to five years old, were used for detecting the time course change of BMD. Since the coefficient of variation (CV(%)) on detecting lumber vertebral (L2-L4) and tibial BMD by DXA was about 0.5%, DXA was useful to detect the change of BMD in beagles. There was a marked decrease in vertebral BMD during lactational period in the control group. The BMD levels after weaning were found to reverse to the initial level at mating. The same tendency was observed in tibial BMD as vertebral BMD, though the BMD changes were not marked. Beagles were administered at a dose of 0.1 microg/kg of 1alpha(OH)D3 three times in a week, and it was found to suppress the decrease in vertebral BMD during the breast feeding period. Also, the administration of 1alpha(OH)D3 promoted the prevention of decreased BMD during lactation both in vertebrae and tibiae. Significant effects of 1alpha(OH)D3 administration on tibial BMD were not observed. No adverse effects, such as hypercalcemia and hypercalciuria, were observed during the experimental period. Therefore, DXA was useful for detecting the changes of BMD in lactating beagles and the change of BMD was marked in lumber vertebrae, which are rich in trabecular bone. The preventive effect of 1alpha(OH)D3 on the decrease of BMD during the lactation period was observed in beagles.

Absorptiometry, Photon↗
PubMed2000

Alfacalcidol inhibits bone resorption and stimulates formation in an ovariectomized rat model of osteoporosis: distinct actions from estrogen.

Although alfacalcidol has been widely used for the treatment of osteoporosis in certain countries, its mechanism of action in bone, especially in the vitamin D-replete state, remains unclear. Here we provide histomorphometric as well as biochemical evidence that alfacalcidol suppresses osteoclastic bone resorption in an ovariectomized rat model of osteoporosis. Furthermore, when compared with 17beta-estradiol, a representative antiresorptive drug, it is evident that alfacalcidol causes a dose-dependent suppression of bone resorption, and yet maintains or even stimulates bone formation, as reflected in increases in serum osteocalcin levels and bone formation rate at both trabecular and cortical sites. 17beta-Estradiol, which suppresses bone resorption to the same extent as alfacalcidol, causes a parallel reduction in the biochemical and histomorphometric markers of bone formation. As a final outcome, treatment with alfacalcidol increases bone mineral density and improves mechanical strength more effectively than 17beta-estradiol, with a more pronounced difference in cortical bone. We conclude that estrogens depress bone turnover primarily by suppressing bone resorption and, as a consequence, bone formation as well, whereas alfacalcidol "supercouples" these processes, in that it suppresses bone resorption while maintaining or stimulating bone formation.

Animals↗
PubMed2000

Hedgehog proteins stimulate chondrogenic cell differentiation and cartilage formation.

Sonic hedgehog (Shh) and Indian hedgehog (Ihh) are important regulators of skeletogenesis, but their roles in this complex multistep process are not fully understood. Recent studies have suggested that the proteins participate in the differentiation of chondrogenic precursor cells into chondrocytes. In the present study, we have tested this possibility more directly. We found that implantation of dermal fibroblasts expressing hedgehog proteins into nude mice induces ectopic cartilage and bone formation. Immunohistological and reverse-transcription polymerase chain reaction (RT-PCR) analyses revealed that the ectopic tissues derived largely if not exclusively from host cells. We found also that treatment of clonal prechondrogenic RMD-1 and ATDC5 cells in culture with Ihh or recombinant amino half of Shh (recombinant N-terminal portion of Shh [rShh-N]) induced their differentiation into chondrocytes, as revealed by cytoarchitectural changes, Alcian blue staining and proteoglycan synthesis. Induction of RMD-1 cell differentiation by Ihh or rShh-N was synergistically enhanced by cotreatment with bone morphogenetic protein 2 (BMP-2) but was blocked by cotreatment with fibroblast growth factor 2 (FGF-2). Our findings indicate that hedgehog proteins have the ability to promote differentiation of chondrogenic precursor cells and that their action in this process can be influenced and modified by synergistic or antagonist cofactors.

Animals↗
PubMed2000

Recurrence of sellar and suprasellar tumors in children treated with hGH--relation to immunohistochemical study on GH receptor.

PURPOSE: GH replacement therapy is required in the majority of children with GH deficiency after treatment of sellar and suprasellar tumors. Owing to the high cell proliferative ability of human GH (hGH), its influence on tumor recurrence has been debated. We retrospectively studied the immunohistochemical expression of the GH receptor in various tumor tissues, in order to investigate the relation between tumor recurrence and hGH replacement. METHODS: GH replacement therapy was performed in 25 patients (8 boys and 17 girls) after the treatment. Tumor recurrence was noted in 4 patients (craniopharyngioma: 2 patients, pilocytic astrocytoma and germinoma: 1 each). Immunohistochemical study of GH receptor in tumor tissue was carried out in those recurrent and recurrence-free cases, by using MAb 263 as a primary antibody. RESULTS: Two patients with recurrent craniopharyngioma were positive for MAb 263, but 1 recurrence-free patient was negative. Patients with pilocytic astrocytoma (recurrent and recurrence-free: 1 each) were all positive. Five patients with germinoma (1 with recurrence and 4 without recurrence) were all negative. CONCLUSION: In the patients with craniopharyngioma treated with GH, a positive immunohistochemical expression of GH receptor in tumor tissue may indicate a high probability of recurrence. In our cases, GH receptor was positive in astrocytomas and negative in germinomas, with or without recurrence. It is therefore speculated that each brain tumor may have its specificity in GH receptor expression.

Adolescent↗
PubMed2000

Incidence of malignant tumors in patients with acromegaly.

Neoplasms may be one of the systemic complications to which we attribute high mortality in acromegaly. The present study was designed to investigate the incidence of malignant tumors in patients with acromegaly in the Japanese population. In this report, 44 patients (25 men and 19 women) with biochemically proven acromegaly were studied retrospectively and had a total 670 patient years of the duration of acromegaly. We investigated the incidence of malignant tumors. There were 5 patients with malignant tumors (5 in men) in this study (11%). Male patients with acromegaly had nearly a 3.5 times higher ratio of malignancy than expected and this increased cancer incidence was considered significant (P=0.01). There was no significant increase in cancer incidence of either the total patient population or female patients. The malignant tumors were two thyroid cancers and one colon, one gastric and one bladder cancer. It is of note that the colon cancer of one patient was diagnosed 2 years after transsphenoidal surgery even though the levels of serum GH and insulin-like growth factor (IGF-1) were reduced to normal after operation. This preliminary study has suggested that male patients with acromegaly might have a high risk of malignancy and that careful screening for tumors is needed both before and after surgical and medical treatment, even in patients with normalized serum GH and IGF-1 levels.

Acromegaly↗
PubMed2000

Pre-and post-operative respiratory assessment of acromegalics with sleep apnea--bedside oximetric study for transsphenoidal approach.

PURPOSE: Although routine mechanical nasal packing after transsphenoidal surgery (TS) is thought to increase respiratory disorders during sleep, there has been little in the literature about the pre- and post-operative airway assessment of acromegalics with sleep apnea (SA). We describe 4 acromegalic patients with SA, who underwent transsphenoidal surgery. METHODS AND CASES: The patients were all men, aged from 47 to 59 years. The pre- and post-operative sleep study consisted with a computer calculated oximetry parameter of oxygen desaturation index (ODI), which was defined as the number/hour of oxygen desaturation episodes exceeding 4% from the base line (normal range < 15). The postoperative (postop.) sleep study was carried out from the 1st postop. day to the 8th day, for 1 to 8 days, varying for each patient. RESULTS: Only the worst postop. result is shown. Patient 1 had 2 operations, 2 years apart. ODI was 39.6 before the 1st operation and 45.9 postop.. In the second operation ODI was 21.8 preoperatively (preop.) and 57.9 postop.. Preop. and postop. ODI was 18.1 and 22.2 in patient 2, 21.6 and 22.5 in patient 3 and 45.5 and 18.9 in patient 4, respectively. ODI of patient 4 was 39.6, 3 weeks later. CONCLUSION: Our data showed that the postop. oxymetric study commonly showed worse results in acromegalics with nasal packing. The better result of patient 4 was probably due to a postop. sleepless state. REM sleep usually increases in the first several postop. days, when cardiopulmonary complications are more likely to occur. Since acromegalics with severe SA and postop. nasal packing may more readily suffer from cardiopulmonary complications, postoperative meticulous respiratory monitoring and care should be mandatory.

Acromegaly↗
PubMed2000

Bone CT evaluation of nasal cavity of acromegalics--its morphological and surgical implication in comparison to non-acromegalics.

PURPOSE: In order to numerically compare the morphological differences of the nasal cavity and nasal sinus between acromegalics and non-acromegalics, bone window CT scans sliced parallel to the transsphenoidal surgical route were performed. MATERIAL AND CASES: Acromegalic patients had small or large macroadenomas and were 13 (7 men and 6 women) in number, aged 53.2 +/- 16.1 years. Non-acromegalic patients had pituitary tumors and were 44 (21 men and 23 women) in number, aged 52.1 +/- 12.5 years. RESULTS: The results of acromegalics are described in comparison to non-acromegalics in parentheses. a) The width of the surgical corridor: piriform aperture, 27.6 +/- 2.7 (25.9 +/- 2.6) mm; origin of inferior nasal concha, 29.4 +/- 9.4 (26.6 +/- 4.0) mm; and origin of middle nasal concha, 29.8 +/- 3.2 (26.2 +/- 4.2) mm. b) The depth of the surgical corridor: the upper lip thickness, 18.1 +/- 2.7 (13.3 +/- 1.4) mm; the distances between piriform aperture and sphenoid wall, 52.9 +/- 4.6 (49 +/- 4.2) mm; sphenoid wall and sellar floor, 17.3 +/- 4.1 (18.7 +/- 4.1) mm; and sellar floor to dorsum sellae, 17.6 +/- 3.4 (15.6 +/- 4.0) mm. c) Marked carotid prominence: 7/13=53.4% (8/44=18.25%). d) Sinusitis: 8/13=61.5% (12/44=27.3%). DISCUSSION & CONCLUSION: The data presented above show that morphological differences in bony nasal cavity and soft tissue may be responsible for a deeper and narrower surgical field for acromegalics. Acromegalics had a marked carotid prominence more frequently, which needs special attention to avoid carotid injury, when enlarging the surgical field. Knowing these morphological differences will provide useful information for peri- and intra-operative care.

Acromegaly↗
PubMed2000

Cavernous sinus invasion and tumor proliferative potential of growth hormone-producing pituitary tumors.

PURPOSE: Surgical removal of growth hormone-producing pituitary adenomas (GHomas) becomes difficult when they invade the cavernous sinus (CS). We investigated the relation among tumor proliferative potential, tumor volume and invasion of GHomas to CS. MATERIALS & METHODS: 15 patients with GHoma aged 20-59 years were enrolled. The volumes of the adenomas were calculated from MR images and the extension to CS was classified into 5 grades according to Knosp's grading system. The immuno-histochemical staining for anti-Ki-67 monoclonal antibody (MIB-1) was performed and the proliferative potential of GHomas was determined as the percentage of MIB-1 labeled nuclei (MIB-1 index). The volume, MIB-1 index and pre-operative growth hormone (GH) level were compared with CS invasion by single and multiple regression analyses. RESULTS: With single regression analyses, CS invasion was significantly correlated with both the volume (r=0.69, p<0.01) and MIB-1 index (r=0.73, p<0.01), but not with the GH level (r=0.42, p=0.12). The volume and MIB-1 index showed a weak correlation but it was not significant (r=0.52, p=0.06). With multiple regression analysis, CS invasion was well explained by the volume and MIB-1 index of GHomas (r=0.82, p<0.01). About 66% of CS invasion was explained by these two factors. CONCLUSIONS: In view of these results, not only the volume but also the speed of growth are important for GHomas to invade CS. GHomas with a high MIB-1 index may, even if they are small, more readily invade CS and need closer post-operative hormonal and neuroimaging studies.

Adenoma↗
PubMed2000

[A case of retroperitoneal schwannoma: diagnostic usefulness of magnetic resonance imaging].

A 36-year-old man visited our hospital with a chief complaint of difficult urination. He was admitted for further examination because ultrasonography showed a heterogeneous solid mass in the lower abdomen. Intravenous urography showed the right ureter and bladder to be pushed leftward without hydronephrosis. Computerized tomography showed a giant solid mass in the retrovesical space. Magnetic resonance imaging revealed a round, well-encapsulated tumor, showing low intensity on the T1-weighted image, heterogeneously high intensity on the T2-weighted image and irregular enhancement with Gd-DTPA. Histopathology of the extirpated tumor was benign schwannoma.

Adult↗
PubMed2000

Thrombopoietin enhances neutrophil production by bone marrow hematopoietic progenitors with the aid of stem cell factor in congenital neutropenia.

We examined the effects of granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), and thrombopoietin (TPO), alone or in combination, on the generation of neutrophils by bone marrow (BM) cells from three patients with severe congenital neutropenia (SCN) through the use of a serum-deprived liquid culture system. Synergistic effects of G-CSF and SCF on the neutrophil production by BM CD34+CD38+c-kit+ cells were observed in SCN patients as well as in normal controls. The addition of TPO to the culture containing G-CSF and SCF further augmented the growth of neutrophils in the two groups. Single-cell culture experiments revealed that the three-factor combination caused increases in both the number and size of neutrophil colonies compared with G-CSF + SCF in normal BM cells, whereas only a significant increment in the colony size was observed in SCN patients. Even in the presence of SCF or SCF + TPO, the concentrations of G-CSF necessary for the substantial production of neutrophils by CD34+CD38+c-kit+ cells were higher in two patients compared with the levels obtained by normal control cells. In addition, TPO did not accelerate the maturation of neutrophilic cells supported by G-CSF + SCF. When BM CD34+CD38-c-kit+ cells were targeted, the addition of TPO to the culture containing G-CSF and SCF was required for significant neutrophil colony growth in the two groups. These results suggest that TPO enhances the G-CSF-dependent neutrophil production with the aid of SCF in this disorder.

ADP-ribosyl Cyclase↗
PubMed1999

Crystal structure of chitosanase from Bacillus circulans MH-K1 at 1.6-A resolution and its substrate recognition mechanism.

Chitosanase from Bacillus circulans MH-K1 is a 29-kDa extracellular protein composed of 259 amino acids. The crystal structure of chitosanase from B. circulans MH-K1 has been determined by multiwavelength anomalous diffraction method and refined to crystallographic R = 19.2% (R(free) = 23.5%) for the diffraction data at 1.6-A resolution collected by synchrotron radiation. The enzyme has two globular upper and lower domains, which generate the active site cleft for the substrate binding. The overall molecular folding is similar to chitosanase from Streptomyces sp. N174, although there is only 20% identity at the amino acid sequence level between both chitosanases. However, there are three regions in which the topology is remarkably different. In addition, the disulfide bridge between Cys(50) and Cys(124) joins the beta1 strand and the alpha7 helix, which is not conserved among other chitosanases. The orientation of two backbone helices, which connect the two domains, is also different and is responsible for the differences in size and shape of the active site cleft in these two chitosanases. This structural difference in the active site cleft is the reason why the enzymes specifically recognize different substrates and catalyze different types of chitosan degradation.

Amino Acid Sequence↗
PubMed1999

Crystal structure of a prokaryotic replication initiator protein bound to DNA at 2.6 A resolution.

The initiator protein (RepE) of F factor, a plasmid involved in sexual conjugation in Escherichia coli, has dual functions during the initiation of DNA replication which are determined by whether it exists as a dimer or as a monomer. A RepE monomer functions as a replication initiator, but a RepE dimer functions as an autogenous repressor. We have solved the crystal structure of the RepE monomer bound to an iteron DNA sequence of the replication origin of plasmid F. The RepE monomer consists of topologically similar N- and C-terminal domains related to each other by internal pseudo 2-fold symmetry, despite the lack of amino acid similarities between the domains. Both domains bind to the two major grooves of the iteron (19 bp) with different binding affinities. The C-terminal domain plays the leading role in this binding, while the N-terminal domain has an additional role in RepE dimerization. The structure also suggests that superhelical DNA induced at the origin of plasmid F by four RepEs and one HU dimer has an essential role in the initiation of DNA replication.

Amino Acid Sequence↗
PubMed1999

Suppression of FRP-1/CD98-mediated multinucleated giant cell and osteoclast formation by an anti-FRP-1/CD98 mAb, HBJ 127, that inhibits c-src expression.

When anti-CD98 mAb 6-1-13, 4-5-1, or 38-2-2 was added to the culture fluids of monocytes, extensive cell aggregation and polykaryocyte formation were induced. These multinucleated giant cells were tartrate-resistant acid phosphatase (TRAP) positive. On the other hand, when monocytes were incubated with another anti-CD98 mAb, HBJ 127, polykaryocyte formation was not detected, although extensive cell aggregation was induced. When HBJ 127 and 6-1-13 were simultaneously added to the culture fluids, anti-CD98 mAb-induced cell fusion was inhibited almost completely. HBJ 127 suppressed formation of 6-1-13-induced cell fusion in a dose-dependent manner. If, however, HBJ 127 was added after incubation of monocytes with mAb 6-1-13 for 6 h, an appreciable degree of TRAP-positive polykaryocyte formation was found. The bindings of 6-1-13 and HBJ 127 were not mutually competed. When monocytes were incubated with 6-1-13 or HBJ 127, 6-1-13 induced c-src mRNA, while HBJ 127 did not. Furthermore, when monocytes were incubated with both 6-1-13 and HBJ 127, c-src mRNA could not be detected, showing that HBJ 127 suppresses c-src expression. Therefore, CD98-mediated osteoclast formation can be regulated by modification of CD98 system.

Antibodies, Monoclonal↗
PubMed1999

Glutathione depletion induces giant DNA and high-molecular-weight DNA fragmentation associated with apoptosis through lipid peroxidation and protein kinase C activation in C6 glioma cells.

Glutathione (GSH) depletion caused by l-buthionine-(S,R)-sulfoximine (BSO) induced apoptosis that was recognized by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick endo-labeling (TUNEL), nuclear DNA staining with fluorescence dye, and internucleosomal DNA fragmentation in C6 rat glioma cells. The BSO-induced cell death was associated with caspase-3 activation. Lipid peroxidation and protein kinase C (PK-C) activation were observed during the apoptosis of C6 cells, and these events were inhibited by antioxidants and iron chelators without affecting BSO-induced GSH depletion. Furthermore, approximately 2 Mbp giant DNA fragments were observed in the BSO-treated cells. The giant DNA fragmentation were followed by approximately 30-700 kbp and then less than 100 kbp, including internucleosomal DNA fragmentations. Such serial DNA degradation was prevented by the antioxidants, the iron chelators, and the PK-C inhibitors. These results suggest that during apoptosis induced by GSH-depletion caused by BSO, reactive oxygen species endogenously produced cause lipid peroxidation and that the lipid peroxidation induced PK-C activation, processes which are thought to be involved in the giant DNA, high-molecular-weight DNA, and the internucleosomal DNA fragmentations.

Animals↗
PubMed1999

Liberation of hydrogen sulfide during the catalytic action of Desulfovibrio hydrogenase under the atmosphere of hydrogen.

The active site of [NiFe] hydrogenase from Desulfovibrio species is composed of a binuclear Ni-Fe complex bearing three diatomic nonprotein ligands to Fe and three bridges between the two metals, two of which are thiolate side chains of the protein moiety. The third bridging atom in the enzyme isolated from D. vulgaris Miyazaki F was suggested to be sulfur species, but was suggested to be oxygen species in D. gigas enzyme. When the hydrogenase from D. vulgaris Miyazaki F was incubated under the atmosphere of H2, H2S was liberated from the enzyme only in the presence of its electron carrier, cytochrome c3 or methylviologen. The amount of H2S liberation was little in the absence of electron carrier or essentially null when the enzyme was incubated under N2. The amount of H2S liberated was about 37% of the hydrogenase contained in the reaction vial in molar basis. These observations are in agreement with the recent observation that the third bridging site at the Ni-Fe active site is vacant in the reduced form of the enzyme revealed by X-ray crystallography.

Alcaligenes↗
PubMed1999

Ectopic bronchus: an insufficiently recognized malformation causing respiratory morbidity in VATER association.

An 11-month-old boy presented with recurrent wheezing and atelectasis in the right upper lobe of the lung. Bronchoscopy and bronchography confirmed an ectopic bronchus arising from the right main bronchus. The diagnosis of VATER association was made on the basis of multiple vertebral and rib anomalies, imperforate anus with a perineal fistula, unilateral hydronephrosis, atrial septal defect, and a preauricular tag, he did not have tracheo-esophageal fistula. We emphasize the importance of recognizing tracheobronchial anomalies in VATER association.

Abnormalities, Multiple↗