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Biomedical subjects

M Kagawa

Publications and source records attributed to M Kagawa.

At least 55 records · Page 3Linked to original sources

Treatment of vasogenic brain edema with arginine vasopressin receptor antagonist--an experimental study.

We determined the effect of a centrally administered V1 receptor antagonist of arginine vasopressin on the brain water content in an animal model of vasogenic brain edema. Using adult rats, a cold injury was induced in the left hemisphere of the brain by applying a frozen copper rod. 50 ng of V1 receptor antagonist was administered into the left lateral ventricle 10 minutes prior to and/or 1 hour after injury. Twenty four hours after the cold injury, the brain water and sodium contents and plasma osmolality were measured. The V1 receptor antagonist significantly suppressed the increase of the brain water and sodium contents in the cortical structure adjacent to the lesion without any changes in plasma osmolality. Our results demonstrate the effectiveness of a V1 receptor antagonist of vasopressin on vasogenic brain edema.

Animals↗

HLA-type of cerebral vasospasm patients after aneurysmal subarachnoid hemorrhage.

We studied human lymphocyte antigen (HLA) types in a group of 45 patients who had aneurysmal subarachnoid hemorrhage (SAH). A significantly increased frequency of HLA antigen A31 and a significantly decreased frequency of HLA antigen B40 were found. In patients with delayed ischemic neurological deficit (DIND) following aneurysmal SAH and HLA typing, HLA-Bw60 antigen showed significant increases; in patients who did not develop HLA-Aw33 and -Cw4 antigens showed significant. Among the patients with Fisher's Group 3 on CT, in particular, these antigens significantly increased when compared with controls from the same geographic area. These results suggest that HLA-Bw60 antigen plays a role as predisposing factor of DIND resulting from vasospasm following aneurysmal SAH, and that HLA-Aw33 and -Cw4 exert protective influence against DIND.

Adult↗

Reversibility of cerebral ischaemia. Dynamic and xenon computed tomography study on ischaemic cerebrovascular disease.

Flow studies using dynamic CT and xenon (Xe) CT were carried out in 25 patients with ischaemic stroke in the territory of the middle cerebral artery to define the clinical characteristics of cerebral ischaemia at a chronic stage. The parameter of peak height/mean transit time (PH/MTT) obtained from dynamic CT can provide an accurate index for blood circulation in the cerebral vascular bed. Xe CT measurements revealed various kinds of ischaemia around the infarction even in the chronic stages. In mild ischaemia of more than 30 ml/100 g/min, reduction of cerebral blood flow (CBF) was well correlated to the PH/MTT. However, in severe ischaemia between 20 and 30 ml/100 g/min, changes of CBF were no longer correlated with the PH/MTT. There were cases showing severe reduction of CBF but which showed sufficient blood circulation (moderate value of PH/MTT). Mild reductions of CBF in parallel with decreased blood supply were often found in the peri-infarct area of infarctions in the centrum semiovale. On the other hand, infarctions in the cortico-subcortical region showed severe ischaemia, in even where blood circulation was relatively well sustained.

Adult↗

Acetylcholine determination of cerebrospinal fluid in aneurysmal subarachnoid hemorrhage.

Acetylcholine (ACh) concentrations were determined serially in cerebrospinal fluid (CSF) obtained from 23 patients with aneurysmal subarachnoid hemorrhage (SAH) by high-performance liquid chromatography (HPLC) with electrochemical detection (ED). The values of CSF ACh were significantly low in the initial stage of SAH, and increased subsequently but they did not return to control values within 3 weeks. In addition, serial measurements of CSF butyrylcholinesterase (BChE) activity in 12 SAH patients showed that the activity was elevated significantly in the initial stage of SAH and returned to control levels within a week. This discrepancy in the recovery period between the ACh levels and the BChE activity in CSF indicated that significantly lower CSF ACh levels after SAH could not be attributed to plasma BChE contamination of CSF. These results suggested central cholinergic dysfunction after SAH, especially in the initial stage.

Acetylcholine↗

Immunohistochemical study of alpha 1-5 chains of type IV collagen in hereditary nephritis.

The distribution of alpha 1-5 chains of type IV collagen [alpha 1-5(IV)] in the glomerular basement membrane (GBM) and epidermal basement membrane (EBM) of 23 families with hereditary nephritis was examined by indirect immunofluorescence. These families were divided into three clinicopathological groups. Group I (10 families) patients showed a widespread "basket weave" pattern of the GBM and a family history of nephritis was present. Group II (6 families) patients showed a widespread "basket weave" change without a family history of nephritis. Group III (7 families) patients showed a widespread attenuation of the GBM but no "basket weave" change, and had a family history of nephritis and chronic renal failure. alpha 1(IV) and alpha 2(IV) were present in all affected and unaffected family members and controls. All normal family members and controls expressed alpha 3(IV), alpha 4(IV) and alpha 5(IV) in the GBM and alpha 5(IV) in the EBM in a diffuse pattern. All group I families and three of the group II families exhibited complete loss of the alpha 5(IV) antigen from the GBM and EBM in male patients, and segmental loss of the alpha 5(IV) antigen in female patients. In these families the alpha 3(IV) and alpha 4(IV) antigens were completely lost from the GBM in male patients with severe nephritis, whereas alpha 3(IV) alpha 4(IV) were present but diminished in male patients with mild nephritis. Three group II and all group III families expressed the alpha 3-5(IV) antigens in an identical manner to that of normal controls. These findings indicate that the heterogeneity of hereditary nephritis reflects a variety of aberrant expression patterns of alpha 3-5(IV) and that immunohistochemical examination of alpha 5(IV) in the EBM is a useful method for the diagnosis of X-linked Alport syndrome.

Adult↗

Influence of ambulatory care rotations on gatekeeping referral patterns of categorical medical residents.

PURPOSE: To determine whether a required ambulatory care block rotation for categorical medicine residents improved their ambulatory care skills and altered their outpatient gatekeeping referral patterns. METHOD: In 1991-92 a prospective cohort study was conducted of 39 categorical medicine residents at the University of California, San Francisco, and their continuity clinic patients. Before and after the residents participated in an ambulatory care block rotation, the residents were surveyed about their ambulatory care skills, and the frequencies and indications for referral of their continuity clinic patients were obtained. Statistical methods consisted of Student's t-test, the Wilcoxon rank-sum test, and Mantel-Haenszel analysis. RESULTS: The 39 residents reported significant improvement in ambulatory care skills. Yet the proportions of the residents' 4,276 patients referred before and after the intervention were 14.2% and 12.4%, respectively (adjusted odds ratio 1.02, p > .9). One-fourth of the referrals were for procedures both before and after the intervention (adjusted odds ratio 1.06, p > .5). CONCLUSION: Despite improvements in the ambulatory care skills of the categorical medicine residents, the residents' gatekeeping referral patterns remained unchanged. Ambulatory care curriculum changes need to be evaluated from the perspective of the trainee and from the perspective of whether these changes influence patient care.

Ambulatory Care↗

Magnetic resonance imaging and quantitative analysis of contents of epidermoid and dermoid cysts.

The intracapsular cholesterol, protein, and calcium contents of epidermoid and dermoid cysts from seven patients were compared with the signal intensities on T1-weighted spin-echo magnetic resonance (MR) images. All specimens had a paste-like consistency when resected. Epidermoid and dermoid cysts demonstrated a wide range of cholesterol and calcium contents, and epidermoid cysts were not always rich in cholesterol. Five patients had cysts with lower signal intensity than white matter, which contained more than 18.3 mg/g wet weight of protein. One of these patients had the highest cholesterol content of all seven patients (22.25 mg/g wet weight) and another had the highest calcium content (0.75 mg/g wet weight). Two patients had cysts with higher signal intensity than white matter, with protein contents of lower than 4.3 mg/g wet weight. High protein content (> 18.3 mg/g wet weight) may decrease signal intensity on T1-weighted MR images, while low protein content (< 4.3 mg/g wet weight) may increase signal intensity in epidermoid and dermoid cysts with high viscosity (paste-like consistency) contents.

Adolescent↗

Type IV collagen alpha 5 chain. Normal distribution and abnormalities in X-linked Alport syndrome revealed by monoclonal antibody.

Although the evidence indicates that mutation of the gene for the alpha 5 chain of type IV collagen, alpha 5-(IV), is the primary defect in X-linked Alport syndrome, protein data for the alpha 5(IV) chain with regard to its normal distribution and its distribution in patients with Alport syndrome is lacking. We produced a rat monoclonal antibody (H51) by immunizing rats with a synthetic peptide corresponding to the nonconsensus amino acid sequence of alpha 5(IV) NC1 domain. H51 reacted by Western blotting with 26-kd cationic monomers and associated dimers of human type IV collagen NC1 domain. Immunohistochemical studies demonstrated that in normal human kidney alpha 5(IV) was present in the glomerular basement membrane and basement membranes of the Bowman's capsule and in some tubules (collecting ducts). The alpha 5(IV) chain was also detected in the basement membranes of normal skin, eye, and lung. Male patients with X-linked Alport syndrome revealed no reactivity of renal and epidermal basement membranes with H51, whereas alpha 5(IV) staining was normal in the glomerular basement membrane of patients with other types of glomerular diseases, including benign familial hematuria. The staining was also normal in the skin of nonaffected males in X-linked Alport families. Female heterozygous for Alport syndrome exhibited a discontinuous or mosaic pattern in the immunofluorescent staining of the epidermal basement membrane. These findings confirm that in patients with X-linked Alport syndrome there are abnormalities in alpha 5(IV) in renal and epidermal basement membranes at the protein level. Immunofluorescent staining of skin biopsies with this antibody may be of value in making a diagnosis of Alport syndrome, and, furthermore, may aid in detecting carrier females in whom urinary abnormalities are often mild or silent.

Adolescent↗

Potential bioactivated neurotoxicants, N-methylated beta-carbolinium ions, are present in human brain.

Potential bioactivated neurotoxicants, 2-N-methyl-beta-carbolinium and 2,9-N,N'-dimethyl-beta-carbolinium ions, as well as N-methylation activities which form these charged species, were analyzed for the first time in the parietal association cortex and the substantia nigra of human brain using GC/MS and HPLC. The brains were taken during forensic autopsies from corpses without obvious degeneration of substantia nigra. In the cortex, 2-methyl-norharmanium ion (2-MeNH) and 2,9-dimethyl-norharmanium ion (2,9-Me2NH) were detected in almost all samples. 2-Methyl-harmanium ions (2-MeHA) and 2,9-dimethyl-harmanium ions (2,9-Me2HA) were detectable in only two samples. In substantia nigra samples pooled from 3 or 4 brains for analysis, 2-MeNH and 2,9-Me2NH levels were higher than those in the cortex, whereas 2-MeHA and 2,9-Me2HA were below detection limits. Their precursors, norharman (NH) and harman (HA), were also measured using HPLC/fluorescence detection. In both regions, NH and HA were present in almost all samples; levels of NH and HA were also significantly higher in the nigra than in the cortex. Using 9-methyl-NH and 2-MeNH as substrates, in vitro N-methylation of the 2[beta] and 9[indole] nitrogens toward beta-carbolines was measured both in the cortex and in the nigra. 2[beta]-N-Methylation activity was significantly higher than 9[indole]-N-methylation activity in both regions. Recent studies show that beta-carbolinium ions resemble the synthetic parkinsonian toxicant, MPP+, with respect to structure and neurotoxic activity. Such 'bioactivated' carbolinium ions could be endogenous causative factors in Parkinson's disease.

Brain Chemistry↗

Immunohistochemical detection of carbohydrate determinant 19-9 (CA 19-9) in intracranial epidermoid and dermoid cysts.

We evaluated carbohydrate antigen (CA) 19-9 levels of intracranial dermoid and epidermoid cyst in serum and intratumoral tissue. The preoperative serum levels were mildly to moderately higher than their normal ranges in four of seven patients. In four patients with high serum CA 19-9 levels, they returned to normal ranges in three who had the cyst resected totally and remained slightly high in one with residual cyst. Immunohistochemical studies using anti-CA 19-9 antibody demonstrated positively stained capsule and keratinous tissue. Serum CA 19-9 levels of intracranial dermoid or epidermoid cysts with more teratomatous components may be elevated above normal levels.

Adolescent↗

Enhancing effect of concomitant L-ascorbic acid administration on BHA-induced forestomach carcinogenesis in rats.

The effects of the synthetic antioxidant butylated hydroxyanisole (BHA) and naturally occurring antioxidants such as L-ascorbic acid (AsA; vitamin C), citric acid, benzoic acid or gallic acid in combination, on the development of rat forestomach epithelial lesions were investigated. A dietary level of 2.0% was selected for all antioxidants and the experimental period was 1 year. As compared with BHA alone, treatment with AsA in combination with BHA increased the severity of the hyperplasia in the mid-region, but not in the prefundic region of the forestomach epithelium, as well as the multiplicity of forestomach tumors. Furthermore, incidences of squamous cell carcinomas (SCCs) in the forestomach were significantly elevated in this group, while papilloma development only showed a tendency to increase. In addition, SCC invasion into the muscle layer of the forestomach was observed only in the BHA + AsA group. Treatment with the other antioxidants did not affect BHA-induced forestomach lesion development. The present study demonstrated that AsA can clearly enhance BHA forestomach carcinogenesis.

Animals↗

Comparison of reversibility of rat forestomach lesions induced by genotoxic and non-genotoxic carcinogens.

Reversibility of forestomach lesions induced by genotoxic and non-genotoxic carcinogens was compared histopathologically. Groups of 30 to 33 male F344 rats were given dietary 0.1% 8-nitroquinoline, dietary 0.4-0.2% 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, an intragastric dose of 20 mg/kg body weight N-methyl-N'-nitro-N-nitrosoguanidine once a week, or 20 ppm N-methylnitrosourethane in the drinking water as a genotoxic carcinogen, or 2% butylated hydroxyanisole, 2% caffeic acid, 2% sesamol or 2% 4-methoxyphenol in the diet as a non-genotoxic carcinogen for 24 weeks. Ten or 11 rats in each group were killed at week 24. Half of the remainder were maintained on basal diet alone for an additional 24 weeks and the other half were given the same chemical for 48 weeks, and then killed. Forestomach lesions induced by genotoxic carcinogens did not regress after removal of carcinogens. In contrast, simple or papillary hyperplasia (SPH), but not basal cell hyperplasia (BCH), induced by non-genotoxic carcinogens clearly regressed after cessation of insult. SPH labeling indices in the non-genotoxic carcinogen-treated cases decreased after removal of the carcinogenic stimulus whereas BCH values were low irrespective of treatment. Atypical hyperplasia (AH), observed at high incidences in rats treated with genotoxic carcinogens, was also evident in animals receiving non-genotoxic agents, even after their withdrawal, albeit at low incidences. AH labeling indices remained high even without continued insult. These results indicate that even with non-genotoxic carcinogens, heritable alterations at the DNA level could occur during strong cell proliferation and result in AH development. This putative preneoplastic lesion might then progress to produce carcinomas.

Animals↗

An autopsied case of Williams syndrome complicated by moyamoya disease.

An 18 year old girl with typical clinical features of Williams syndrome suddenly died of intracerebral hemorrhage due to moyamoya disease. Autopsy revealed vascular abnormalities, such as supravalvular aortic stenosis (SAS) and an abnormal complicated cerebrovascular network in the cerebral arteries. The arterial wall of the SAS lesion consisted of thickened medial tissue showing elastic disorganization with prominence of the smooth muscle cells. The narrowed vessels of the circle of Willis showed intimal thickening with an extremely wavy internal elastic lamina and marked thinning of the media. To our knowledge, this is the first report of moyamoya disease associated with Williams syndrome.

Abnormalities, Multiple↗

Clinical analysis of incidentally discovered unruptured aneurysms.

BACKGROUND AND PURPOSE: We analyzed the risk factors for rupture of an intracranial aneurysm based on a retrospective angiographic study of ruptured and unruptured aneurysms. METHODS: The 44 cases of asymptomatic aneurysms were selected from 1612 patients whose lesions had been discovered fortuitously by angiography (2.7%) during the period from 1980 to 1989. All these patients were free from any sign of intracranial aneurysm. The variations in age, sex, and location of the aneurysms were analyzed compared with 638 ruptured aneurysms that had been treated in our institute during the same period. The size, shape, and arterial geometry of the unruptured aneurysms were examined angiographically. RESULTS: Unruptured aneurysm was discovered fortuitously in 44 (2.7%) of 1612 patients, with greater incidence in women aged older than 60 years. Unruptured aneurysms were less likely to occur in the anterior communicating artery (12.8%) and the middle cerebral artery (6.4%). However, they were frequently found in the internal carotid artery, with an incidence of 10.6% in cavernous portion of the internal carotid artery, 19.1% in the internal carotid-ophthalmic artery, 19.1% in the internal carotid-posterior communicating artery, and 12.8% in the internal carotid-anterior choroidal artery. Seven of the nine internal carotid-posterior communicating artery aneurysms showed a hypoplastic or aplastic posterior communicating artery. The mean diameter of the unruptured aneurysms was 4.8 mm, and 80% were smaller than 6 mm. CONCLUSIONS: Intracranial aneurysms are formed not only at the bifurcation of an artery but also at its branching and bending points. However, an aneurysm located at the bifurcation, such as the anterior communicating artery and the middle cerebral artery, bleeds easily in contrast with lateral aneurysms such as those found at the branching and bending points on the internal carotid artery.

Adolescent↗

Management of adult moyamoya disease.

The surgical management of adult moyamoya disease was evaluated retrospectively. Eight of 10 patients with hemorrhagic stroke had no bleeding episodes and eight of 11 patients with ischemic stroke were asymptomatic postoperatively. Angiography demonstrated neovascularization via the external carotid artery (ECA) in 22 sites (88%) and reduced basal moyamoya vessels in 11 sites (44%) postoperatively. These symptomatic improvements and angiographic findings suggest that reconstructive surgery for adult moyamoya disease patients with hemorrhagic or ischemic stroke is effective in decreasing hemodynamic stress in the basal moyamoya vessels and increasing the cortical blood supply via the ECA.

Adult↗

[The effect of arginine vasopressin receptor antagonist on the rat cold-injured brain].

Centrally released arginine vasopressin (AVP) has been reported to increase the water permeability of brain capillaries under both normal and pathological conditions. It is not known, however, whether AVP regulates the permeability of brain capillaries via a V1 receptor or a V2 receptor. In the present experiments, we attempted to suppress cold-induced brain edema with V1 or V2 receptor antagonists. Adult rats were intraventricularly administered with 5 ng, 50 ng, or 500 ng of V1 receptor antagonist, or 50 ng or 500 ng of V2 receptor antagonist. Ten minutes after administration, a cold injury was induced in the left hemisphere of the brain by applying a freezing probe, which had been cooled by liquid nitrogen, to the left parietal skull for 20 seconds. Brain water and tissue sodium content were then measured 24 hours after the cold-injury. In experiment 1, the brain water content had significantly increased in both the injured and non-injured hemispheres. The administration of 50 ng of V1 receptor antagonist resulted in a significant reduction in the brain water content of the bilateral hemispheres. Administration of 50 ng of V2 receptor antagonist produced a significant reduction in the brain water content of the non-injured hemisphere only. A 500 ng administration of both antagonists did not change the brain water content of the bilateral hemispheres. In experiment 2, we divided the cold injured brain into cortical and deep structures and observed the effect of the V1 receptor antagonist. Cold-injury induced significant increases in brain water and the tissue sodium content of the bilateral cortical structures, but no changes in bilateral deep structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗