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Biomedical subjects

T Hosoya

Publications and source records attributed to T Hosoya.

At least 163 records · Page 9Linked to original sources

Allergenic epitopes of ovalbumin (OVA) in patients with hen's egg allergy: inhibition of basophil histamine release by haptenic ovalbumin peptide.

We studied allergenic determinants that induce hypersensitivity to OVA, the major allergen in egg allergy, using immunoblot and histamine release assays. Immunoblot analysis demonstrated a part of the OVA epitope was in the C-terminal region comprising residues 347-385 (OVA347-385). Histamine was released from basophils of a patient with egg allergy upon stimulation with the OVA fragment corresponding to OVA347-385. Furthermore, detailed epitope mapping using overlapping peptides (residues 347-366, OVA-A; residues 357-376, OVA-B; and residues 367-385, OVA-C) in the OVA 347-385 region was carried out using the histamine release assay. In order for histamine release from basophils to occur, the allergen must possess two or more allergenic determinants located on the protein molecule at distances that would be equivalent to the distances between IgE molecules on the membrane surface. these results suggest that there are at least two epitopes that bind IgE antibodies on each OVA peptide. In addition, one epitope that binds IgE antibodies in two patients appears to reside in the haptenic peptide OVA357-366 (OVA-B1). The histamine release from basophils stimulated by OVA-B was completely inhibited by OVA-B1 in one of these patients. Similarly, OVA-B1 inhibited the histamine release produced by OVA-A in the other by more than 40%. These results suggest that haptenic synthetic peptides could regulate the allergic reaction in the effector phase if common epitope(s) recognized by IgE antibodies in the patients with egg allergy can be found. These are the first studies that provide an antigen-specific approach to inhibiting histamine release from basophils by a haptenic peptide recognized by IgE antibodies in an allergic disorder.

Allergens↗

Defective organification of iodide causing congenital goitrous hypothyroidism.

A 26-yr-old Japanese woman with congenital goitrous hypo-thyroidism and sensorineural deafness underwent a thyroidectomy. Examination of the thyroid gland revealed characteristic features of multinodular goiter. The T3 and T4 content in thyroglobulin (Tg) were 0.03 and 0.02 mol/mol Tg, respectively. Iodide incorporation into Tg, using slices of the thyroid tissue, revealed that iodide organification of thyroid tissue from our patient was markedly lower than that of normal controls. Then, guaiacol and iodide oxidation activities of thyroid peroxidase (TPO) in our patient's thyroid tissue were lower than those of normal controls (guaiacol assay: 1.92 vs. 30.0 +/- 5.7 mGU/mg protein; iodide assay: 1.1 vs. 6.6 +/- 2.8 mIU/mg protein). Lineweaver-Burk plot analysis of the oxidation rates of guaiacol and iodide indicated that this patient's TPO had a defect in the binding of guaiacol and iodide, but the coupling activity of the patient's TPO was not decreased compared with those of two normal thyroids. In this case and in control subjects, Nothern gel analysis of TPO messenger RNA from unstimulated and TSH-stimulated thyroid cells revealed a 3.2 kilobase species in the former and four distinct messenger RNA species of 4.0, 3.2, 2.1, and 1.7 kilobases in the latter. Western blot analysis of TPOs obtained from this patient and from control subjects identified the same 107 kDa protein, using antimicrosomal antibody-positive serum. We analyzed the coding sequence in the patient's TPO gene by using polymerase chain reaction technique. A single point mutation of G-->C at 1265 base pair was detected only in the TPO gene, but this point mutation does not alter the amino acid residue. It is possible that posttranslational modification such as abnormal glycosylation may occur in the TPO molecules. Furthermore, it is possible that there are differences in the tertiary structures of the TPO molecules between our patient and normal subjects. The above abnormalities of TPO molecules may play an important role in our patient's dyshormonogenesis.

Adult↗

Epi-cochlioquinone A, a novel acyl-CoA : cholesterol acyltransferase inhibitor produced by Stachybotrys bisbyi.

A novel acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor, designated epi-cochlioquinone A has been isolated from the fermentation broth of Stachybotrys bisbyi SANK 17777. The molecular formula, physicochemical properties, NMR spectroscopic analysis and X-ray crystallographic analysis revealed that this compound was a stereoisomer of cochlioquinone A, which has been previously reported as a nematocidal agent. It inhibited ACAT activity in an enzyme assay using rat liver microsomes with an IC50 value of 1.7 microM. However, it showed about 10-fold less potent inhibitory effect on plasma lecithin cholesterol acyltransferase (LCAT) than on ACAT. In addition, it inhibited in vivo cholesterol absorption in rats by 50% at 75 mg/kg.

Animals↗

Schizostatin, a novel squalene synthase inhibitor produced by the mushroom, Schizophyllum commune. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

In the process of screening for squalene synthase inhibitors from microbial fermentation products we have isolated a novel compound, named schizostatin (Fig. 1), from the culture broth of the mushroom, Schizophyllum commune SANK 17785. Schizostatin inhibited rat liver microsomal squalene synthase dose dependently and the IC50 value was 0.84 microM. The inhibition was competitive with respect to farnesylpyrophosphate with a Ki value of 0.45 microM.

Alkyl and Aryl Transferases↗

[A case of pituitary adenoma progressing to pituitary apoplexy on the occasion of cerebral angiography].

A case of pituitary adenoma which had progressed from subclinical pituitary apoplexy to subacute pituitary apoplexy on the occasion of cerebral angiography is reported. A 29-year-old man, complaining of bitemporal hemianopsia, was admitted to our department. Plain skull X-p revealed enlargement and double floor of the sella turcica. No abnormal calcification was revealed. CT demonstrated an isodensity mass with a diameter of 4 x 4 cm, and with ring enhancement in the suprasellar region. The mass extended from the intrasellar region to the suprasellar region and had a signal of high intensity on T1-weighted images. Endocrinological examination revealed hyperprolactinemia with a serum level of 422 ng/ml and normal reaction of anterior pituitary hormones. On 3rd March, digital subtraction angiography with 5F catheter was performed with the patient under sedation. The contrast medium was ioxaglic acid (Hexabrix 320). A volume of 6 ml with a speed of 4 ml per second was injected for the internal carotid angiogram. A total volume of 60 ml was used. Serum saline with 10 unit per ml of heparin sodium was also used for flushing. During angiography, the patient's blood pressure was 125/60-115/60mm Hg. DSA revealed upward displacement of the proximal portion of the anterior cerebral artery, pocket formation, and staining of the tumor capsule. Six hours later, he complained of retroorbital headache. Next morning, he noticed complete lack of left visual acuity. On 7th March, right visual acuity degenerated to blindness. CT revealed that the mass had increased its density. With bifrontal osteoplastic craniotomy, the tumor with marked intratumoral hemorrhage was resected. Its histology was chromophobe adenoma. The patient's right visual acuity improved rapidly. On the occasion of cerebral angiography, we could observe that subclinical pituitary apoplexy deteriorated to subacute pituitary apoplexy. Rosenbaum postulated that injection of contrast media increased intravascular pressure leading to pituitary apoplexy. At present, we cannot postulate increased intravascular pressure with 5F catheter and DSA. We cannot rule out that, with underlying subclinical pituitary apoplexy, hemorrhagic infarction due to contrast media and the anti-coagulate effect of heparin sodium accelerated the intratumoral bleeding. Subclinical pituitary apoplexy is a vulnerable state because of its aggravation to symptomatic apoplexy under mild stress. We emphasize that an operation should be performed as early as possible in the case of subclinical pituitary apoplexy.

Adenoma↗

[An assessment of the thalamocortical sensory pathway based on small infarcts in the corona radiata on CT].

Although lacunar syndrome is relatively commonly encountered in patients with a lacunar infarct in the deep cerebral white matter, the responsible lesions are often unidentified. By examining eight patients with lacunar syndrome who had small infarcts in the deep cerebral white matter, an attempt was made to determine the position and distribution of the sensory pathway on brain CT at the level of the splenium of the corpus callosum. When the distance from the frontal crista to the superior saggital sinus sulcus was defined as 1.0, the position of the corticospinal tract was located in the portion from 0.45 to 0.49 and that of the sensory pathway in the portion from 0.49 to 0.53. These data indicated that the position of the sensory pathway was just behind the corticospinal tract and the distribution was very narrow at this level. The results of this assessment revealed that lacunar infarcts in the deep cerebral white matter were liable to cause sensorimoter syndrome more than pure sensory stroke.

Aged↗

[Clinical usefulness of three-D cerebral mensional MR imaging in the diagnosis of medullary venous malformation].

Medullary venous malformation (MVM) is one of the most common vascular malformations encountered pathologically. In fact, it is generally discovered incidentally during the workup of other disorders. In 18 cases (19 lesions) of MVM, we evaluated retrospectively the diagnostic value of CT and MRI. We set four evaluations, excellent, good, fair and poor, to assess the diagnostic value of each imaging method. Contrast enhanced CT and pre-contrast MRI could detect the abnormality in 80% of the cases, but it was difficult to demonstrate the umbrella like medullary vein. Contrast enhanced MRI showed the umbrella sign in 60%. Images reformated with three-dimensional (3-D) MR imaging were better able to demonstrate this structure. Medullary vein collection, drainage into a single central vein and termination into a superficial cortical vein or a dural sinus were clearly demonstrated in all cases. Thus, all cases were diagnosed correctly as MVM. Contrast enhanced 3-D MR imaging was superior to other imaging techniques except angiography.

Adolescent↗

[A case of mycotic ICA petrous portion aneurysm treated with endovascular surgery].

A case is reported of mycotic aneurysm at the petrous portion of the internal carotid artery (ICA) treated with an endovascular procedure. A sixty-seven-year-old male who had suffered from chronic otitis media bilaterally for the last five years showed a sudden onset of massive left otorrhagia. Cerebral angiogram at the eighth day of otorrhagia disclosed a big aneurysm at the petrous portion of the left ICA. The aneurysm was round in shape but its wall was irregular. The angiogram also showed that a stenotic finding of the left ICA just at the proximal portion of the aneurysm and the neck of the aneurysm was not broad. Bone window computed tomography showed a destroyed petrous bone around the left ICA. The results of the Matas test and the Allcock test told us that left ICA occlusion should not be selected as a treatment. We decided that endovascular surgery could be applied as the treatment of this pathology. An endovascular procedure was performed for this pathology one month after the otorrhagia. The aneurysm was successfully embolized using platinum coils beside a part of the neck without occlusion of the parent artery. The patient's postoperative course was not eventful. We concluded that endovascular surgery might be the first choice for the treatment of an ICA petrous portion mycotic aneurysm.

Aged↗

[A case of Iotrolan encephalopathy].

A case of Iotrolan encephalopathy is reported. A 66-year-old woman, suffering from subarachnoid hemorrhage, was admitted to our department on January 17th, 1995. After an operation for aneurysmal clipping and ventriculo-peritoneal shunt, she was discharged with no neurological deficiency. CT scan revealed ventricular enlargement and slight periventricular lucency. She was re-admitted on January 4th, 1996. She was suffering from nausea, vomiting, right hemiparesis, right hemi-hypesthesia and disturbance of consciousness. CT scan demonstrated right thalamic bleeding and bilateral ventricular hemorrhage. Further ventricular enlargement was also revealed. With medical treatment, her symptoms were relieved gradually. But disorientation and memory disturbance continued. Shuntography with Iotrolan was performed on February 2nd, 1996. The ventriculo-peritoneal shunt was demonstrated to be occluded on the abdominal side. The volume of Iotrolan used was about 8cc. She became very restless on the night of the examination. Her temperature was up to 38. CT on February 4th demonstrated brain penetration of the Iotrolan. Revision of ventriculo-peritoneal shunt, administration of steroids and hydration was performed. CSF findings demonstrated no abnormalities. Her symptoms were relieved gradually. Iotrolan is a non-ionic contrast media of dimer type, composed of C37 H48 I6 N6 O18. Its distinctive features are low distributing coefficient and high affinity with water. Contrasting several reports of Metrizamide encephalopathy, only 2 cases of Iotrolan encephalopathy were reported. Iotrolan is reported to be much safer than Metrizamide. We were able to find brain penetration by Iotrolan. It is expected to be a characteristic radiological finding of encephalopathy induced by contrast media. The mechanism of Iotrolan encephalopathy is obscure. Several theories concerning Metrizamide encephalopathy are proposed. These are (1) inhibition of hexokinase, (2) inhibition of acethylcholinesterase, (3) immunological mechanism and (4) vascular disturbance. Iotrolan has no 2-deoxy-glucose structure. The inhibition theory of hexokinase is least expected. Related matters are circulatory disturbance of liquor, dehydration, excessive contrast media, advanced age, diabetes mellitus, hypertension, epileptic patients and patients taking phenothiazines. Prompt therapy is important. Removal of contrast media, hydration and administration of steroids should be performed as early as possible.

Aged↗

[Correlation of regional cerebral blood flow between Xe-CT and 133Xe-SPECT: validity of Xe-CT in evaluating rCBF].

Stable xenon-enhanced computed tomography (Xe-CT), a relatively inexpensive addition of an inhalation system to the CT, has been a common method for the measurement of rCBF in recent years. Although the 133Xe clearance method has been accepted as a standard method since the 1970s, a comparative study of rCBF between Xe-CT and 133Xe-SPECT has not been reported. We studied the validity of Xe-CT for evaluating rCBF in comparison with 133Xe-SPECT. From May 1993 to December 1994, rCBF studies in 31 cases were performed using both methods within one month of each other. We evaluated rCBF of the unilateral cerebral hemisphere at a slice of OM + 80 mm level. Finally, Eleven cases were excluded from the analysis because of the existence of ventricle in the image and/or discrepancy in the clinical state between the two examinations. In the remaining 20 cases, there was a significant correlation of rCBF between Xe-CT (Y) and 133Xe-SPECT(X)(Y = 0.95X-1.7, r = 0.86, p < 0.001, n = 40). The results supported the usefulness of Xe-CT for the quantitative assessment of rCBF. As compared with SPECT, Xe-CT offers the advantages of much higher spatial resolution, allowing more precise reference of flow and anatomy, and providing quantitative information on rCBF in deeper regions of the brain.

Brain↗

[A case of acute occlusion of the cervical portion of the right internal carotid artery with successful stepwise vascular dilatation by rescue PTA and deferred PTA].

A case is reported of acute occlusion of the cervical portion of the internal carotid artery, which was recanalized and dilated by steps through rescue percutaneous transluminal angioplasty (PTA) and deferred PTA. A 53-year-old man, complaining of progressive disturbance of consciousness and hemiplegia, was admitted to our department at about 7 hours after onset. CT demonstrated no abnormality. Digital subtraction angiography revealed an occlusion of the right cervical internal carotid artery. After intra-arterial injection of t-PA, a guide wire was able to be passed through the artery. Recanalization of internal carotid artery was performed by rescue PTA with Stealth FS angioplastic balloons of small diameter. Residual stenosis ratio was about 80%. After rescue PTA, his symptoms improved. On the following day, deferred PTA with Stealth FS angioplastic balloons of larger diameter was performed. Stenosis ratio was 30%. After the procedure, his palsy was relieved. DSA in the 3rd week after the PTA revealed that the stenosis ratio had changed from 30% to 13%. Rescue PTA is very effective for prompt recanalization. Stepwise vascular dilatation by rescue PTA with small balloons followed by deferred PTA can improve symptoms and prevent fatal hemorrhagic infarction. This method is especially useful for high risk patients of cervical internal carotid artery occlusion.

Acute Disease↗

[Hyperuricemia and the kidney].

The risk for renal insufficiency by uric acid precipitation in medulla of kidney correlates with the degree of uric acid supersaturation in the urine, depending on uric acid concentration and urinary pH. The patients with gout or hyperuricemia have sometimes acidic urine and increased uric acid excretion. Accordingly, these patients frequently accompany by renal insufficiency. Improvement of hyperuricosuria, increasing of urine volume, and alkalinization of urine to pH6 6.5, are effective for the prevention from renal insufficiency. Acute renal failure related to hyperuricemia, can also occured secondary to cell lysis. Tumor lysis syndrome is a critical illness characterized by massive tumor cell death leading to severe hyperuricemia, hyperphosphatemia, hypocalcemia, and acute renal failure after starting chemotherapy to cancers, especially lymphoproliferative malignancies. Administration of allopurinol 500-600 mg and adequate hydration and alkalinization of urine are advocated to prevent acute renal failure. Intensive care with hemodialysis is often required to treat renal failure, because renal failure is reversible in most cases.

Acute Kidney Injury↗

[Metabolic disorder of purine nucleotide in patients with renal disease].

The serum levels of uric acid, hypoxanthine and xanthine tended to increase with the decrease of renal function. This mechanism was thought to be the decreased excretion of these materials from the kidney. More than ninety percent of the patients with renal insufficiency (Ccr < or = 30 ml/min) showed hyperuricemia. In general, the gouty arthritis was reported to be uncommon in the patients with secondary hyperuricemia due to renal insufficiency. However, the frequency of gouty arthritis was reported to be high in the patients with polycystic disease and lead nephropathy. The therapeutic standard for secondary hyperuricemia with renal insufficiency was not established. Allopurinol is the drug of choice for controlling hyperuricemia due to renal insufficiency in many cases. In renal insufficiency, the drug must be used cautiously and in reduced dosage because increased serum concentration of oxipurinol, active metabolite of allopurinol, may induce severe side effect.

Allopurinol↗

Effects of mixed solvents on three elementary steps in the reactions of horseradish peroxidase and lactoperoxidase.

The effects of methanol, acetone, and ethylene glycol (up to 50% v/v) on elementary steps in the reactions of horseradish peroxidase (HRP) and lactoperoxidase (LPO) were studied by means of the stopped-flow method and the difference spectrum. The rate constant (k3,app) of the oxidation reaction of p-cresol with HRP compound II was remarkably reduced in the presence of organic solvents (to 2.3%, 1.8% and 9.4% of the original value in the presence of 50% (v/v) of methanol, acetone and ethylene glycol, respectively), then to a lesser degree were decreased the rate of the oxidation reaction with LPO compound II, and the rate of the oxidation reaction with HRP compound I. These reductions in the reaction rates were not due to competitive inhibition of the solvents, but considered to be related to the degree of exposure of the electron transfer route to the medium. While the rate constant of compound I formation (k1,app) was moderately affected by organic solvents in the case of HRP, the reaction rate with LPO was scarcely affected by organic solvents, being in harmony with the compact heme crevice which probably hampers penetration of solvent molecules. The rate constant (k2,i,app) of the oxidation reaction of an iodide ion by HRP compound I was also hardly affected by the solvents. On the basis of these facts, the mechanism of electron transfer from donors to compound I and compound II is discussed.

Acetone↗

glial cells missing: a binary switch between neuronal and glial determination in Drosophila.

In the Drosophila CNS, both neurons and glial are derived from neuroblasts. We have identified a gene, glial cells missing (gcm), that encodes a novel nuclear protein expressed transiently in early glial cells. Its mutation causes presumptive glial cells to differentiate into neurons, whereas its ectopic expression forces virtually all CNS cells to become glial cells. Thus, gcm functions as a binary switch that turns on glial fate while inhibiting default neuronal fate of the neuroblasts and their progeny. Similar results are also obtained in the PNS. Analyses of the mutant revealed that "pioneer neurons" can find correct pathways without glial cells and that neurons and glia have a common molecular basis for individual identity.

Amino Acid Sequence↗

Cloning, characterization, and tissue distribution of porcine SPAI, a protein with a transglutaminase substrate domain and the WAP motif.

The primary and gene structures and tissue distribution of porcine SPAI-2, a protein that belongs to the WAP protein superfamily and has a sodium-potassium ATPase inhibitory activity, were determined by molecular cloning and Northern analysis. A full-length cDNA clone was isolated from a porcine duodenum cDNA library. The cDNA insert encoded a polypeptide of 187 amino acids, which is composed of three domains: a hydrophobic presequence of 21 amino acids, a prosegment of 105 amino acids ending with Asp126, and the mature SPAI-2 sequence of 61 amino acids beginning with Pro127. The prosegment contained 16 repeats of a hexapeptide that is highly homologous to the repetitive sequence found in the transglutaminase domain of the human elafin, an elastase-specific inhibitor that also belongs to the WAP superfamily. The repetitive sequence was demonstrated to be a good substrate of transglutaminase using a recombinant preparation produced in Escherichia coli. A porcine genomic library was then screened for the SPAI gene. Characterization and sequencing of positive clones indicated that the gene is similar to the elafin gene, having 3 exons encoding the 5'-untranslated region and signal sequence, proSPAI, and 3'-untranslated region, respectively. Northern blot analysis revealed intestine-specific expression of SPAI mRNA; the message was especially abundant in the small intestine. ProSPAI was also found in the circulation. The similarity of proSPAI to elafin in the domain structure, the acid-labile nature of the cleavage site (Asp126-Pro127), and the fact that the major form of SPAI in the plasma is proSPAI strongly suggest that proSPAI is not the precursor but rather it is the native form of SPAI. Like elafin, therefore, SPAI appears to be a new type of biologically active substance with a transglutaminase substrate domain that acts as an anchoring sequence.

Amino Acid Sequence↗

Three-dimensional-MRI of neurovascular compression in patients with hemifacial spasm.

We prospectively studied 30 patients to assess the usefulness of three-dimensional (3D) contrast-enhanced MRI in patients with hemifacial spasm. In all patients neurovascular compression of the facial nerve could be detected. Microvascular decompression was performed in 14, and vascular compression of the root exit zone of the facial nerve and the offending artery were exactly as predicted by MRI in all but 2. We also retrospectively studied whether the symptomatic side could be defined only by enhanced 3D MRI in 55 randomised individuals (30 with and 25 without hemifacial spasm). All symptomatic sides were correctly identified, and the false-positive rate was 13.8%.

Adult↗