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Biomedical subjects

A Fujikawa

Publications and source records attributed to A Fujikawa.

27 records · Page 2Linked to original sources

Further metabolism of FK506 (tacrolimus). Identification and biological activities of the metabolites oxidized at multiple sites of FK506.

To characterize the metabolic pathway of FK506 (tacrolimus), FK506 or its 31-O-desmethyl metabolite was incubated with liver microsomes prepared from dexamethasone-treated rats in the presence of a NADPH-generating system under aerobic conditions. Besides the four oxidized metabolites already reported, four new metabolites were isolated and identified by HPLC, mass spectrometry, and NMR spectroscopy, and their biological activities were examined. The di-demethylated metabolites at the 15- and 31-, 13- and 31-, and 13- and 15-methoxy groups of FK506, were designated respectively as M-V, M-VI, and M-VII. The fourth, M-VIII, was the metabolite produced after O-demethylation at the 31-methoxy group and formation of a fused 10-membered ring structure through the 19- to 22-carbon of the macrolide ring after oxidation of the 19-methyl group, and of the 36- and 37-vinyl group of FK506. The immunosuppressive activity of the isolated metabolites was estimated in a mouse mixed lymphocyte reaction system and the IC50 values for M-V, M-VI, M-VII, M-VIII, and FK506 were > 1000, 8.78, > 1000, 15.27, and 0.11 ng/ml, respectively. Reactivity of the metabolites with mouse anti-FK506 monoclonal antibody was studied and immunocrossreactivity of M-V was 92.3% of FK506, but no reactivity was observed for M-VI, M-VII, and M-VIII. FK506 thus was metabolized at multiple sites by rat hepatic microsomes and the metabolites formed (M-V) - (M-VIII) exhibited weak or negligible immunosuppressive activity.

Animals↗

Cloning and expression of cDNA coding for a new allergen from the house dust mite, Dermatophagoides farinae: homology with human heat shock cognate proteins in the heat shock protein 70 family.

An immunoreactive clone, which shares no homology with the major allergens, Der f I and Der f II, was isolated by screening of a Dermatophagoides farinae cDNA library with rabbit antiserum raised against an extract of the house dust mite and sera from patients with mite allergy. The deduced amino acid sequence of the cDNA of the clone is significantly homologous, up to 65.5%, to the carboxyl-terminal region of the heat shock cognate protein (hsc) 71 in the heat shock protein (hsp) 70 family. A pool of the recombinant protein-specific IgE purified from mite-allergic sera recognized a 67 kDa protein on a blot of ATP-binding components partially purified from the mite body extract, while the antibody did not bind to the major allergens. We conclude that the recombinant protein, one of several important allergens, may be a protein in the heat shock protein 70 family from the house dust mite, D. farinae.

Allergens↗

[A case of Hangman's fracture associated with vertebral arteriovenous fistula treated with trapping].

A case of a traumatic vertebral arteriovenous fistula associated with a hangman's fracture is reported. A 45-year-old male fell down about 2 meters and struck his parietooccipital region against the ground. Profuse nasal bleeding developed. He was transferred to a local hospital, where his respiration was ataxic and blood pressure was low. After intubation, he was transferred to our emergency department. Cervical x-p revealed fracture of C1, C2 and subluxation of C2 body. Because of uncontrollable nasal bleeding, the bilateral maxillary arteries were embolized with spongel. At this time, right vertebral angiograms demonstrated a vertebral arteriovenous fistula with an pseudoaneurysm located at C2 level. On the 13th hospital day, direct balloon occlusion of the fistula was attempted; this could not be achieved because the subclavian and vertebral arteries were tortuous and the balloon catheter could not be introduced to the level of the fistula in the vertebral artery. The patient was only observed until follow-up angiogram on the 24th hospital day revealed enlargement of the pseudoaneurysm. We performed trapping of both the proximal and distal ends of the involved vertebral artery; from C5 to C1. Postoperative course was uneventful, hangman's fracture was fixed with a Halo vest. Four months after operation, fistula and pseudoaneurysm were not opacified on angiogram. We believe that transvascular techniques are the treatment of choice for vertebral arteriovenous fistulas. However, as the next best thing, we can use trapping for the patient whose vessels are too tortuous to introduce the balloon catheter to the involved vessel.

Arteriovenous Fistula↗

[A case of intracerebral AVM fed by the anterior ethmoidal artery].

Only 27 cases of dural AVM fed by the anterior ethmoid artery have been reported in the literature. Their nidi were usually in the dura mater. In our case, the nidus was located in the brain parenchyma, although its feeder was the dural artery. A 75-year-old man was admitted to our department because of disturbed consciousness. CT scan showed intracerebral hemorrhage in the left frontal region with ventricular perforation, and subarachnoid hemorrhage in the suprasellar cistern. Left carotid angiography revealed an AVM in the anterior cranial fossa, fed by the anterior ethmoidal artery and drained by a cortical vein, which was dilated with some vascular sacs. A left frontal craniotomy was performed. The subcortical hematoma was removed, and then, after retracing the frontal lobe, two feeders penetrating the dura mater were identified and clipped. The nidus of the AVM with aneurysmal vascular dilatation could be seen on the cortical surface. It was coagulated and removed en-bloc. Histologically, the malformation consisted of thickened dilated veins and distorted small arteries. Postoperative angiography revealed no vascular anomaly. The patient was discharged with mild aphasia and mild right hemiparesis.

Aged↗

[Traumatic primary brain stem injury and ambient cistern hematoma evaluated with magnetic resonance imaging].

Traumatic hemorrhage in the ambient cistern is thought to be an indirect indication of brain stem injury. In many cases such brain stem lesions cannot be clearly demonstrated by conventional CT scans. Magnetic resonance imaging (MRI) provides a more sophisticated display of the brain stem with improved contrast resolution of structures not appreciated on CT. We present four patients with traumatic ambient cistern hematoma on CT. They showed consciousness disturbance at the initial neurological examination and a Glasgow Coma Scale (GCS) of 7-10. All patients had hemothorax or clavicular fracture ipsilateral to the ambient cistern hematoma that suggested a severe mechanical force from the same direction. Axial, coronal and sagittal MRI scans were obtained with a super-conductive 1.5 T unit (Picker) within 6 days after trauma. Two standard pulse sequences were used; (1) Spin-echo (TR/TE = 500/20) or Inversion Recovery (TR/TI/TE = 3300/600/30) to obtain T1-weighted information and (2) Spin-echo (TR/TE = 2000/100) to obtain T2-weighted information. In case 1 (3-year-old girl) the hematoma which was thought to be located in the ambient cistern on CT was found to be present in the subpial region in the tegmentum on MRI. On T2 weighted image, a high signal intensity area was seen in the perifocal area. This area was demonstrated as a low density area on CT. This patient has remained in a persistent vegetative state 6 months after trauma. In case 3 (31-year-old man) CT demonstrated no abnormal findings in the brain stem. MRI demonstrated a high intensity area in the right cerebral peduncle and left tegmentum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Guide-wire-directed detachable balloon: clinical application in treatment of varicoceles.

Wire-directed detachable balloons were used in embolization treatment of varicoceles in six patients. Advancement of the balloon over a guide wire allowed easy embolization of the internal spermatic vein at the level of the inguinal ring. Additional detachable balloons were used to occlude the collateral vessels to the varicocele. This method proved highly effective in embolization of tortuous veins and in placement of multiple balloons.

Adolescent↗

Infrared absorption spectra ranging from 2.5 to 10 microns at various layers of human normal abdominal aorta and fibrofatty atheroma in vitro.

The infrared absorption spectra ranging from 2.5 to 10 microns in wavelength at various layers of both the human normal abdominal aorta wall and the fibrofatty atheroma were measured by conventional transmission spectrophotometry. Optical specimens 7 microns in thickness were prepared using a cold microtome. Pathological examination was simultaneously performed to identify tissue type of the optical specimen. We found that the presence of characteristic absorption peaks at 5.75 and 3.4 microns was restricted to the atheromatous (fibrofatty) layer of the aorta wall. These peaks may be attributed to the accumulated cholesterol deposits. We also discovered that the normal media layer had strong absorption at 6.05 microns. The discrimination between normal media, fibrofatty atheroma, and aged intimal tissue was made possible by the normalized peak ratio which was based on the ratio of the 5.75- and 6.05-microns absorption peaks. These results may be significant for selective laser ablation of atheromatous tissue, as well as tissue diagnosis, to prevent artery perforation during laser angioplastic procedures.

Aged↗

Choroidal detachment after vitreous surgery.

BACKGROUND AND OBJECTIVE: To study the frequency and clinical features of choroidal detachment (CD) after vitreous surgery, because there have been no reports on this problem. PATIENTS AND METHODS: We studied the clinical features of 14 patients (15 eyes) with CD from a total of 380 patients treated with vitrectomy at the Nagasaki University Hospital from January 1994 to August 1997. RESULTS: The incidence of CD after vitreous surgery was 3.9% (15/380). The reasons for vitrectomy were 6 retinal detachments, 4 proliferative diabetic retinopathies, and 5 others. During vitrectomy, 4 eyes were treated with scleral buckling, 11 with endolaser photocoagulation, and 3 with cryoretinopexy. Retinal detachment as a postoperative complication was seen in 8 patients, and in 5 of them the retina remained detached after the final treatment. CONCLUSIONS: CD may be caused by scleral buckling, panphotocoagulation, or stress on the ciliary body. Some patients with CD have a poor outcome.

Adult↗