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Biomedical subjects

R Kawai

Publications and source records attributed to R Kawai.

At least 19 recordsLinked to original sources

Follow-up MRI in dural arteriovenous malformations involving the cavernous sinus: emphasis on detection of venous thrombosis.

Six patients with a dural arteriovenous malformation (dural AVM) involving the cavernous sinus were followed up with magnetic resonance imaging in order to assess change in the lesions. Spin-echo (SE) imaging of three patients in whom the AVM appeared to have closed at least 1 month earlier (two of them spontaneously, and one after external carotid artery embolization) showed neither apparent flow void in the involved cavernous sinus nor evidence of venous thrombosis. SE images of the other three patients who had not been cured by external carotid artery embolization (two of whom were examined within a week of treatment), detected persisting arteriovenous shunts, including high-flow cortical venous drainage, seen as flow void. Two-dimensional time-of-flight MR angiography (2D TOF MRA) was performed simultaneously in three patients. Whereas shunting blood and the normal cavernous sinus were of high intensity, presumed thrombosed cavernous sinuses were isointense with stationary brain tissue. SE imaging can confirm the resolution of arteriovenous shunts, but poorly delineates very acute and chronic thrombosis of the draining veins. In contrast, 2D TOF MRA directly demonstrates flowing blood, permitting the diagnosis of venous thrombosis; it should be included in follow-up of a dural AVM involving the cavernous sinus when venous thrombosis is suspected.

Adult

Cervical discs are most susceptible to beta 2-microglobulin amyloid deposition in the vertebral column.

Intervertebral discs of 41 chronic renal failure autopsy cases were examined histologically and immunohistochemically to assess the distribution of beta 2-microglobulin-associated (beta 2m) amyloid in the vertebral column. The results demonstrated beta 2m amyloid to appear first in the cervical discs, then in the lumbar and upper thoracic discs, and finally in the middle and lower thoracic discs as the dialysis period is prolonged. The shortest dialysis period for which beta 2m amyloid was detected was one year and seven months. Deposition of beta 2m amyloid was most remarkable in the C4-5, 5-6, and 6-7 levels, which are known to sustain severe mechanical stress in daily life. Thus it is suggested that local mechanical stress accelerates beta 2m amyloidosis. A marked macrophage reaction was observed around the amyloid in cases of severe amyloidosis, the macrophages themselves being immunohistochemically positive for IL-1 beta and TNF-alpha. Amyloid deposition and reactive inflammation mediated by cytokines appear to be closely related to the pathogenesis of destructive spondyloarthropathy.

Adult

Disseminated cryptococcosis presenting with adrenal insufficiency and meningitis: resistant to prolonged antifungal therapy but responding to bilateral adrenalectomy.

A case of disseminated cryptococcosis with features of primary adrenal insufficiency and meningitis in an immunocompetent host is presented. Despite antifungal chemotherapy, neither meningitis nor bilateral adrenal gland enlargement was improved. Aspiration biopsy of the adrenal gland revealed necrotic tissue with numerous fungi, suggesting that the adrenal glands were the focus of the persistent fungemia. Removal of bilateral adrenal glands led to improvement by making the patient more sensitive to antifungal chemotherapy.

Adrenal Gland Diseases

[Inflammatory cell infiltration around beta 2-microglobulin amyloid deposition: histologic comparison of beta 2-microglobulin amyloidosis with AA or AL amyloidosis].

Thirty-one autopsy cases of beta 2-microglobulin (beta 2M) amyloidosis were pathologically investigated in comparison with 17 autopsy cases of AA or AL amyloidosis. In 20 cases (65%, 20/31) of beta 2M amyloidosis, inflammatory cells, mainly macrophages were seen infiltrating around beta 2M amyloid in intervertebral disks. The more beta 2M amyloidosis advances, the more macrophage infiltration tends to be prominent. In cases of severe beta 2M amyloidosis, the cytoplasm of macrophages around amyloid deposition were swollen with engulfed amyloid substance and were often transforming to foreign body multinucleated giant cells. In addition, granulation tissue was formed with infiltrating macrophages, foreign body multinucleated giant cells, capillary proliferation and fibrosis around beta 2M amyloid deposition. On the other hand, inflammatory cell infiltration around amyloid deposition was scarcely seen in AA or AL amyloidosis. Ultrastructurally, macrophages were abundant in phagocytic vacuoles containing amyloid fibrils. These macrophages were immunohistochemically positive for CD68, IL-1 beta and TNF-alpha. Thus, macrophage infiltration around beta 2M amyloid is thought to be responsible for local pain and tissue destruction of dialysis patients.

Amyloid

Regional brain measurement of Bmax and KD with the opiate antagonist cyclofoxy: equilibrium studies in the conscious rat.

Brain distribution of the opiate receptor antagonist, cyclofoxy (CF), was evaluated at equilibrium in rats. A combination of i.v. injection and constant i.v. infusion was used to administer CF over a wide dose range (2.4-450 nmol/rat). Kinetic simulations and experimental results showed that this administration schedule accomplishes "true" tissue-blood equilibrium of CF within 60 min. To estimate the receptor-ligand binding parameters, we assumed that the CF concentration at the receptor site is identical to that in plasma water at equilibrium, and can be calculated from measured blood data after corrections for radiolabeled metabolites and plasma protein binding. This assumption was supported by CSF and plasma water measurements at equilibrium. Regional KD, Bmax, and a nonspecific tissue binding equilibrium constant (Keq) were estimated by fitting the tissue and plasma water concentrations to a single receptor model; the estimated values were 1.4-2.9 nM, 15-74 pmol/g of tissue, and 5.2-8.0, respectively. They are in good agreement with previous in vitro measurements (Rothman and McLean, 1988) as well as in vivo estimates from i.v. injection experiments (Sawada et al., 1990c). The conventional method to estimate the receptor-ligand binding parameters using data from cerebellum to approximate nonspecific tissue binding was found to be unacceptable. Although cerebellum is a brain region with no opiate receptors in rats, small differences in nonspecific tissue binding in different brain regions resulted in significant overestimations of KD and Bmax with this method. Receptor-active and -inactive enantiomers [[18F](-)-CF and [3H](+)-CF)] were simultaneously administered to the same animal and the receptor-bound CF concentration could be accurately measured; this method was used to estimate Bmax from a single study in a single animal and has potential for direct application in human studies using positron emission tomography.

Animals

Kinetic analysis of transport and opioid receptor binding of [3H](-)-cyclofoxy in rat brain in vivo: implications for human studies.

[3H]Cyclofoxy (CF: 17-cyclopropylmethyl-3,14-dihydroxy-4,5-alpha-epoxy-6-beta-fluoromorp hinan) is an opioid antagonist with affinity to both mu and kappa subtypes that was synthesized for quantitative evaluation of opioid receptor binding in vivo. Two sets of experiments in rats were analyzed. The first involved determining the metabolite-corrected blood concentration and tissue distribution of CF in brain 1 to 60 min after i.v. bolus injection. The second involved measuring brain washout for 15 to 120 s following intracarotid artery injection of CF. A physiologically based model (Sawada et al., 1990a) and a classical compartmental pharmacokinetic model (Wong et al., 1986a) were compared. The models included different assumptions for transport across the blood-brain barrier (BBB); estimates of nonspecific tissue binding and specific binding to a single opiate receptor site were found to be essentially the same with both models. The nonspecific binding equilibrium constant varied modestly in different brain structures (Keq = 3-9), whereas the binding potential (BP) varied over a much broader range (BP = 0.6-32). In vivo estimates of the opioid receptor dissociation constant were similar for different brain structures (KD = 2.1-5.2 nM), whereas the apparent receptor density (Bmax) varied between 1 (cerebellum) and 78 (thalamus) pmol/g of brain. The receptor dissociation rate constants in cerebrum (k4 = 0.08-0.16 min-1; koff = 0.16-0.23 min-1) and brain vascular permeability (PS = 1.3-3.4 ml/min/g) are sufficiently high to achieve equilibrium conditions within a reasonable period of time. Graphical analysis (Patlak and Blasberg, 1985) of the data is inappropriate due to the high tissue-loss rate constant (kb = 0.03-0.07 min-1) for CF in brain. From these findings, CF should be a very useful opioid receptor ligand for the estimation of the receptor binding parameters in human subjects using [18F]CF and positron emission tomography.

Animals

Nerve root avulsion of birth palsy: comparison of myelography with CT myelography and somatosensory evoked potential.

Findings at myelography and computed tomographic (CT) myelography were reviewed in 21 patients (22 limbs) with birth palsy; nerve root shadows were the focus of this study. Myelography demonstrated 51 completely avulsed roots (78%) and 14 incompletely avulsed roots (22%). A traumatic meningocele was detected at 38 roots on myelograms and 51 roots on CT myelograms. Thirteen avulsed roots (eight completely and five incompletely avulsed roots) (20%) were not associated with a meningocele. In nine patients who underwent brachial plexus exploration, myelographic findings were compared with root somatosensory evoked potential (SEP). SEP was not induced at 22 of 25 completely avulsed roots and was induced at all seven incompletely avulsed roots. Myelography and SEP were consistent in 29 of 32 roots (91%). It is concluded that myelography is indispensable for preoperative evaluation of cervical nerve root avulsion of birth palsy, because CT myelography is not sensitive to nerve root avulsion without a traumatic meningocele, and SEP cannot enable one to discriminate incomplete avulsion from intact roots.

Brachial Plexus

[Myelography for nerve root avulsion in birth palsy].

Myelography and CT myelography (CTM) were reviewed in 18 cases of birth palsy with clinically suspected avulsion injury. Root-somatosensory evoked potential (root-SEP) was also reviewed for myelographic evaluation of the nerve root avulsion in birth palsy. Root-SEP is not induced in case of avulsed nerve roots, but is induced in case of both normal and incompletely avulsed roots. Myelography demonstrated 58 abnormal nerve roots in 18 cases (19 limbs); 45 (78%) complete and 13 (22%) incomplete nerve root avulsions. Each of complete and incomplete avulsions was defined as total absence and partial presence of rootlets on myelography, respectively. Traumatic meningoceles were detected at 46 roots (79%) on myelography and/or CTM; 35 roots on myelography and 45 roots on CTM. CTM could not detect only a very small meningocele at one root. At 11 roots CTM was superior to myelography in delineating a meningocele because CTM is sensitive to a poorly enhanced meningocele. CTM, however, could not diagnose nerve root avulsions so accurately as myelography, since myelography detected 12 (7 completely and 5 incompletely) avulsed roots without meningocele, whereas CTM could not delineate the nerve roots clearly. Thus, myelography is indispensable to evaluate nerve root avulsions without meningocele. Root-SEP was examined in 9 patients who underwent brachial plexus exploration. SEP was negative at 22/25 roots with complete avulsion and was positive at 7/7 roots with myelographically incomplete avulsion, regardless of presence or absence of any traumatic meningocele.(ABSTRACT TRUNCATED AT 250 WORDS)

Child

Computed tomographic findings of nasopharyngeal carcinoma with skull base and intracranial involvement.

Twenty-nine patients with nasopharyngeal carcinoma (NPC) with skull base or intracranial involvement were analyzed by high-resolution computed tomography (CT). We divided the path of the primary tumor spread into six directions from the nasopharynx. The most common direction of spread was the anterior region, and the second most common was the posterolateral region. Recently, high resolution CT has been used for the diagnosis of the nasopharynx. T-staging of NPC was made according to the International Union Against Cancer (UICC) TNM classification system, depending on clinical findings and conventional radiograph examinations (not including CT). CT images were valuable for detection of the primary tumor involvement of the skull base region in NPC. Furthermore, bone target CT images were better for searching for subtle bony changes. Therefore, we recommend that CT should be used in T-staging of NPC systematically. When CT is used as one of the staging criteria, some patients with NPC with subtle bony changes will be upstaged.

Adolescent

Proliferation of 3T3-L1 preadipocytes in a completely defined serum-free medium.

We have developed a completely defined serum-free medium that supports the growth of Swiss 3T3-L1 fibroblasts to nearly the same extent as Dulbecco's modified Eagle's medium supplemented with 10% fetal calf serum. With ASF301 medium [former name, RITC 80-7; Yamane et al. Exp. Cell Res. 134, 470 (1981)], most of the 3T3-L1 cells survived for at least 10 days, but did not grow. ASF301 medium contains insulin and mouse-epidermal growth factor as growth factors, which are termed "progression factors". So we examined the effects of "competent factors" on the proliferation of 3T3-L1 preadipocytes. Growth in the medium supplemented with competent factors reached a confluent monolayer in 6-7 days. Furthermore, it was confirmed that 3T3-L1 cells grown in the serum-free medium retained the properties of differentiation into adipocytes. Our serum-free medium should be a useful tool for research on the growth and differentiation of 3T3-L1 preadipocytes.

Adipose Tissue

Preparation and biological evaluation of 18F-labeled benzamide analogs as potential dopamine D2 receptor ligands.

Three 18F-labeled benzamide derivatives were prepared and evaluated as potential ligands to study the dopamine D2 receptor phenomenon. The compounds are analogs of iodobenzamide, eticlopride and raclopride and are labeled with an N-2-[18F]fluoroethyl functionality on the pyrrolidine ring. The compounds were tested in vitro for binding affinity and found to exhibit somewhat lower affinity than the non-fluorinated analog. In vivo distribution studies revealed that all compounds were more highly bound to plasma proteins than was raclopride. In addition, compartmentation of radioactivity demonstrated nonspecific binding to be the predominate retention in the brain as reflected by the low caudate to cerebellum ratios for these compounds. These three 18F-labeled benzamide derivatives are inferior to raclopride and iodobenzamide for studies of the D2 receptor system using positron emission tomography.

Animals

BBB transport and rapid tissue binding of cyclofoxy: comparison of active and inactive enantiomers.

The "rapid-phase" brain distribution of 3H-labeled enantiomers of the opiate receptor antagonist cyclofoxy (CF), receptor active (-) and inert (+) forms, was measured during 20- to 180-s intravenous infusion in rats. [14C]iodoantipyrine was coinfused during these experiments to obtain a simultaneous measure of blood flow. The influx clearance (K1) across the blood-brain barrier (BBB) and the rapid binding equilibrium constant (Keq) were estimated in different brain regions for both enantiomers (2-compartmental model); a possible receptor binding process (k3) was also examined for (-)-CF (3-compartment model). K1 (0.46-0.91 ml.min-1.g-1), the capillary permeability-surface area product (PS; 0.75 approximately 1.4 ml.min-1.g-1) and the tissue extraction fraction (E; 0.6-0.7) were found to be identical for both enantiomers in the nonreceptor binding model; Keq was identical in cerebellum but larger for (-)-CF in other brain structures. The difference in Keq between the enantiomers (2-compartment model) correlated with the rank order of opiate receptor density observed in vitro and in vivo. These results suggest that concomitant use of (-)-CF and (+)-CF will be useful for in vivo receptor binding analyses.

Animals

Kinetic analysis of the opiate antagonist cyclofoxy in rat brain: simultaneous infusion of active and inactive enantiomers.

The opiate antagonist (-)-cyclofoxy [(-)-CF] and the receptor inert enantiomer (+)-CF were radiolabeled with 18F or 3H and administered to conscious Sprague-Dawley rats; an isotope effect was not observed. Constant i.v. infusion of both 18F-(-)-CF and 3H-(+)-CF in tracer amounts showed a marked difference in the tissue level of 18F-(-)-CF among various brain structures, whereas the values for 3H-(+)-CF were lower and much less variable. Co-infusion of unlabeled (-)-CF (1 mg/rat) did not change the tissue binding of 3H-(+)-CF in any brain structure, but reduced that of 18F-(-)-CF to the same level as 3H-(+)-CF. These results demonstrate an identical nonspecific tissue binding for (+)- and (-)-CF in vivo, and suggest that (+)-CF can be used to measure the "nonspecific" component of (-)-CF binding in brain. A nonlinear analysis of the 3H-(+)-CF data indicated the presence of both "instantaneous" and time-dependent components in nonspecific tissue binding and that nonspecific binding varied 1.5-fold in different brain structures. The combined 3H-(+)-CF and 18F-(-)-CF data were fitted to a four-compartment model, which includes parameters for capillary transport, "instantaneous" and time-dependent nonspecific tissue binding, as well as receptor association and dissociation. The receptor-association rate constant varied considerably in various structures of cerebrum (2.0-8.7 min-1), whereas receptor dissociation was estimated within a narrow range (0.12-0.17 min-1). The receptor binding potential (receptor association/dissociation) ranged between 12.7 and 56.2 and was in good agreement with previous estimates in vitro.

Animals

[Radionuclide studies of the early stage of chronic interstitial pneumonitis].

Radionuclide studies for the interstitial lung disease were surveyed in this article. On the ventilation-perfusion study, high V/Q mismatches are seen in advanced stage. A bolus inhalation method of small amount of Kr-81 m gas is useful to detect the impairment of thoraco-pulmonary compliance in the early stage of chronic interstitial pneumonitis (CIP). Ga-67 scintigraphy is indispensable for early detection and assessing the activity of CIP. During the last few years, the assessment of epithelial permeability using Tc-99m-DTPA is performed to evaluate morphological damage of pulmonary parenchyma in interstitial pulmonary diseases. Clinical significance of I-123-IMP scintigraphy was also surveyed.

Amphetamines

External carotid artery embolization of dural arteriovenous malformations involving the cavernous sinus. Outcome and role of venous thrombosis.

Nine patients with dural arteriovenous malformations (AVMs) in the region of the cavernous sinus were treated by means of external carotid artery (ECA) embolization using polyvinyl alcohol. All AVMs received vascular supply from both the ECA and the internal carotid artery. Seven cases were clinically cured after embolization, while 2 cases with cortical venous drainage and high flow through the shunt were not completely cured. Venous thrombosis was observed in 5 cases before and in 9 after embolization. In 6 cases the drainage pattern changed owing to venous thrombosis. Complete thrombosis of the cavernous sinus was found on a follow-up angiography in 2 cases. Formation of venous thrombosis and occlusion of feeding arteries are crucial factors for success of ECA embolization. Dural AVMs with cortical venous drainage and high flow cannot be relieved by ECA embolization alone owing to difficulty in obtaining thrombosis of the veins.

Adult

[Evaluation of CT myelography and conventional myelography for avulsion injury of nerve root--18 cases of birth palsy].

CT myelography (CTM) and conventional myelography were reviewed in 18 cases of birth palsy with clinically suspected avulsion injury. A traumatic meningocele was detected in 45 roots by CTM, and in 35 roots by myelography. CTM misinterpreted only one root with a very small meningocele. CTM was superior to myelography in delineating a traumatic meningocele, because CTM is sensitive to a poorly enhanced meningocele. On the other hand, CTM missed 9 avulsed roots without a meningocele. By myelography, these 9 roots were diagnosed as 6 roots of complete avulsion injury and 3 roots of incomplete avulsion. Myelography is indispensable in evaluating nerve root avulsion.

Child

[Adverse reactions and intracranial contrast medium after myelography].

Correlation between adverse reactions and intracranial contrast media after myelography was studied. Myelography was carried out for 12 cases with metrizamide and 14 with iotrolan. In all patients, cranial CT scans were performed 18 approximately 22 hours after myelography. CT attenuation value of subarachnoid cistern was higher than the gray matter in 12 cases and lower in 14 cases. Six cases suffered from adverse reactions, but only 1 case belongs to the higher group. No correlation between adverse reactions and residual amount of contrast medium on CT was recognized.

Adult