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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

Successful treatments of lung injury and skin burn due to hydrofluoric acid exposure.

Recent growth in the electronics and chemical industries has brought about a progressive increase in the use of hydrofluoric acid (HF), along with the concomitant risk of acute poisoning among HF workers. We report severe cases of inhalation exposure and skin injury which were successfully treated by administering a 5% calcium gluconate solution with a nebulizer and applying 2.5% calcium gluconate jelly, respectively. Case 1: A 52-year old worker used HF for surface treatment after welding stainless steel, and was hospitalized with rapid onset of severe dyspnea. On admission to the critical care medical center he had widespread wheezing and crackles in his lungs. Chest radiograph showed a fine diffuse veiling over both lower pulmonary fields. Severe hypocalcemia with high concentrations of F in serum and urine were disclosed. He was immediately given 5% calcium gluconate solution by intermittent positive-pressure breathing (IPPB), utilizing a nebulizer. On the 21st hospital day, chest film and CT scan did not demonstrate any abnormality. He was discharged very much improved on the 22nd hospital day. Case 2: A 35-year old worker at an electronics factory was admitted to his local hospital with severe skin burn on his face and neck after exposure to 100% HF. Treatment began with immediate copious washing with water for 20 min. Calcium gluconate 2.5% gel (HF burn jelly) was applied to the area as a first-aid measure. Persistent high concentrations of serum and urinary F were disclosed for 2 weeks. After treatment with applications of HF burn jelly, he was confirmed as being completely recovered. The present cases and a review of published data suggest that an adequate method of emergency treatment for accidental HF poisoning is necessary.

Administration, Topical↗

Partial seizures in leukoencephalopathy with swelling and a discrepantly mild clinical course.

We report a patient with 'Leukoencephalopathy with swelling and a discrepantly mild clinical course', an entity of leukoencephalopathy recently clarified. Our patient presented with complex partial seizures in addition to characteristic radiological findings and clinical course. A review of the literature revealed that this new neurodegenerative disease complicates epilepsy in more than half of the patients, and that partial components in the seizure symptomatology are not infrequent.

Adolescent↗

Co-segregation of benign infantile convulsions and paroxysmal kinesigenic choreoathetosis.

We report seven families and two sporadic cases in which benign infantile convulsions and paroxysmal kinesigenic choreoathetosis were co-segregated. Clinical investigations included physical and neurological examinations, blood electrolyte values, interictal and ictal electroencephalograms, and computed tomography or magnetic resonance imaging of the brain. The family pedigree was confirmed and the clinical history of the relatives was obtained. Seventeen individuals developed infantile convulsions followed by paroxysmal dyskinesias during childhood or adolescence. Six had only infantile convulsions, and two had only paroxysmal dyskinesias. The seizures never persisted into childhood or recurred in adulthood. The seizure type was a complex partial seizure, with or without secondary generalization, in nine of 14 patients. Paroxysmal dyskinesias, a subgroup of paroxysmal kinesigenic choreoathetosis, occurred for less than 5 min. The attacks of dyskinesias began at age 5-12 years in most patients, and tended to remit in adulthood. The mode of inheritance was apparently autosomal dominant in four of the families (17 affected individuals), who were diagnosed with ICCA syndrome (infantile convulsions and paroxysmal choreoathetosis). However, the condition occurred only among siblings in three families (six patients), and sporadically in two patients, suggesting genetic heterogeneity in this distinct co-segregation.

Adolescent↗

Isoflavonoids from Pueraria mirifica and their estrogenic activity.

Nine isoflavonoids including a new pterocarpene, puemiricarpene, were isolated from the tuberous root of Pueraria mirifica (Leguminosae). The structure of puemiricarpene was determined by spectroscopic means. Estrogenic activity of the isolated isoflavonoids was tested using MCF-7 human breast cancer cells. Moderate activity was observed for kwakhurin, a prenylated isoflavonoid.

Estrogens, Non-Steroidal↗

How do the x-ray structure and the NMR structure of FMN-binding protein differ?

The crystal structure of FMN-binding protein (FMN-bp) from Desulfovibrio vulgaris Miyazaki F was solved by the multiple isomorphous replacement method and refined to an R factor of 15.1% at 1.3 A resolution. FMN-bp exists in a dimeric form in the crystal, in contrast to the monomeric structure determined by NMR. R.m.s. deviations between the crystal structure and the solution structure are more than 2 A, which implies significant differences. There are some hydrophobic residues in the interface between the two monomers. In particular, Leu122 in the C-terminus has a close contact with the o-xylene moiety of FMN, while solvent molecules may cover the o-xylene moiety in the solution structure.

Bacterial Proteins↗

Preliminary X-ray crystallographic study of DsrD protein from the sulfate-reducing bacterium Desulfovibrio vulgaris.

DsrD (dissimilatory sulfite reductase D) protein encoded by the dsr operon of the sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough has been crystallized using the vapour-diffusion method with ammonium sulfate as a precipitating agent. The crystals diffract to 1.7 A resolution and belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 60.54 (6), b = 65. 20 (4), c = 46.41 (3) A. The crystal contains two DsrD molecules per asymmetric unit, giving a Matthews coefficient (V(M)) of 2.6 A(3) Da(-1). A gold-derivative (NaAuCl(4)) crystal has been successfully prepared.

Crystallization↗

Local and chronic application of PTH accelerates tooth movement in rats.

We previously reported that whereas systemic continuous infusion of parathyroid hormone (PTH) accelerated orthodontic tooth movement, systemic but intermittent injection of PTH did not increase the rate of tooth movement. Analysis of these data suggested that continuous administration of PTH could be applicable for orthodontic therapy. In the present study, we investigated whether local and chronic application of PTH(1-34) would accelerate orthodontic tooth movement. To increase the residence time of PTH in the injected area, we used methylcellulose (MC) gel (2% W/V) for a slow-release formulation of PTH. MC gel containing PTH (PTH-MC) continuously released biologically active PTH into the acceptor medium for more than 72 hrs in vitro. When male rats received a local injection of PTH-MC into the subperiosteum in the mesio-palatal region of the maxillary first molar (M1) every other day, M1 movement, which was mesially drawn by an orthodontic coil spring attached to the maxillary incisors, was accelerated in a dose-dependent manner. PTH-MC injection at 1 microg/400 g body weight caused a 1.6-fold increase in the rate of tooth movement. The acceleration of tooth movement by PTH-MC injection was marked on days 6, 9, and 12. Local injection of PTH dissolved in saline without MC did not significantly accelerate tooth movement on day 6 or later. Histological examination revealed active osteoclastic bone resorption and a widened periodontal space on the compression side of the periodontal tissue in the PTH-MC-injected rats. These results suggest that local injection of PTH in a slow-release formulation is applicable to orthodontic therapy.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗