Biomedical subjects
Publications and source records attributed to S Sugimoto.
We report a left acute subdural haematoma caused by rupture of a left anterior cerebral artery aneurysm, which progressed to left hemiparesis. Coronal MRI was superior to CT for visualizing Kernohan's notch.
A teratological study of suplatast tosilate (IPD-1151T), a newly developed anti-allergic agent, was carried out in pregnant NZW rabbits to assess the effects on dams and fetuses. IPD-1151T was administered to dams orally at dose levels of 0, 100, 300, 450 and 700 mg/kg/day from day 6 through day 18 of gestation, and their fetuses were removed for teratological evaluation. The results were as follows: 1. In dams, marked increase in the incidence of abortion, and decrease in body weight gain, food consumption and feces mass were shown in the 700 mg/kg/day group. Slight decrease in body weight gain and food consumption were seen in the 450 mg/kg/day group, but no toxicities were observed in the 300 mg/kg/day or less groups. 2. In fetuses, marked increase in embryo-fetal deaths and decrease in alive fetal body weights and placental weights, but no teratogenicity were shown in the 700 mg/kg/day group. There were no fetal toxicity or teratogenicity in the 450 mg/kg/day or less groups. 3. No effective dose levels were 300 mg/kg/day for maternal general toxicity and 450 mg/kg/day for maternal reproductive toxicity and for fetuses.
Antigenicity of suplatast tosilate (IPD-1151T) was investigated in guinea pigs and mice. The results were as follows: 1. Homologous passive cutaneous anaphylaxis (PCA), active systemic anaphylaxis (ASA), active cutaneous anaphylaxis (ACA) and Schultz-Dale reaction tests were carried out using guinea pigs which were immunized orally with IPD-1151T alone or subcutaneously with IPD-1151T and Freund's complete adjuvants (CFA). Positive reactions in these tests were not produced by eliciting injection of IPD-1151T or its metabolite, M-1. On the other hand, the sensitization of ovalbumin (OVA) with CFA produced positive reactions in all of PCA, ASA, ACA and Schultz-Dale tests. 2. Heterologous passive cutaneous anaphylaxis (PCA) test using rats was carried out using two strains of mice (C3H/He and BALB/c) which were immunized orally with IPD-1151T alone or intraperitoneally with IPD-1151T and aluminum hydroxide gel (Alum) as an adjuvant. No animals showed positive reaction to both eliciting antigens, IPD-1151T and M-1. On the other hand, a positive reaction in PCA test to eliciting antigen, OVA, was obtained in rats treated with sera of mice sensitized with OVA plus Alum. 3. These findings showed that IPD-1151T had no antigenicity in guinea pigs and mice.
The clinical course and computed tomographic (CT) findings of 23 patients with brain tumors manifesting as tumoral hemorrhage were reviewed. The most common symptoms were headache and clouding of consciousness. A CT finding of a lesion located next to a solid or irregular clot indicated intratumoral hemorrhage. Precontrast CT demonstrating an indent on the hematoma surface was a valuable indicator of tumoral hemorrhage. A CT finding of accumulated levels of blood/fluid or a hyperdense mass containing small hematoma indicated intratumoral hemorrhage, and obscure hyperdensity indicated intratumoral hemorrhagic infarction. Such findings were often difficult to distinguish from spontaneous intracerebral hemorrhage due to other factors. The incidence of rebleeding from residual tumors was high, carrying a very poor prognosis, so radical removal of brain tumors with hemorrhage is very important.
The study was aimed at comparing the effects of dobutamine (dob) and dopamine (dop) on isotonic contraction and rhythmicity of isolated guinea-pig papillary muscles (in oxygenated Tyrode at 37 degrees C), by taking into account: 1) the rate of stimulation (50% above the diastolic threshold) at 5 fixed periods: (RR: 1600, 1200, 1000, 800 and 400 ms); 2) 7 log concentrations (logC) of the index amine (from 10(-9) to 10(-3) M). To this end, a dose-relation protocol which explored the effects of all 5 RR and 7 logC was designed and 15 adult female Guinea-pigs (250 to 350 g) were randomized to either the dob (n = 8) or the dop (n = 7) arm. This enabled a total of 525 sets of data to be analyzed: in 38 sets (7.2%) premature contractions (CP) were coded. CP were sustained (freq: > 3) in 25 of these latter 38 sets (4.8%). Compared to the basal state, the amplitude (AMP%) and the log of percent amplitude (logAMP%) and time to peak (TP%) changes of the isotonic (Gould transducer) twitch were calculated along with the log of this latter variable (logTP%). AMP%, log AMP%, TP% and logTP% were linearly correlated with logC at all RR. In the range 1600-400 RR, for both amines, significant linear correlations (magnitude of 0.15 > r < magnitude of 0.70, 0.001 > p < 0.022) were seen for plots of AMP%, logAMP% and TP%:steeper correlations were observed for dop. This was confirmed in multivariate analysis (BMDP-9R) whereby AMP%, logAMP%, TP%, logTP%, CP, and freqCP were dependent variables and coded variables were included to either define the type of treatment (dop versus dob) or logC. In these analyses, logC (t > 11) and dop (t > magnitude of 3) might be used to explain (0.28 > r2 < 0.42, 0.00001 > p < 0.0025) AMP% and logAMP%, meaning that a different inotropic (isotonic) efficacy exists between these 2 amines, at all logC. On the other hand, when CP and freqCP were coded, explanatory variables were AMP% and logAMP% (4.86 > t < 6.95, 0.06 > r2 < 0.09, p < 0.00001), but not the variable used to code the type of treatment (dob versus dop).(ABSTRACT TRUNCATED AT 400 WORDS)
In this paper we reported a familially occurred cavernous angiomas (CA) of the central nervous system (CNS). Case 1 was a 14-year-old female with an initial symptom of transient motor and sensory disorders of the right upper extremity. On examination she had a cutaneous angioma and no neurological deficit. CT and MRI revealed two lesions in the brain. These lesions were removed surgically and were diagnosed histologically as CA. Case 2 was a 45-year-old female, the mother of case 1, with a long standing headache. She had a cutaneous angioma and no neurological deficit. CT and MRI revealed a CA in the brain and a one in the cervical cord. Case 3 was an 11-year-old female, the cousin of case 1, with an initial symptom of left hemiparesis. On examination, she had a cutaneous angioma and left hemiparesis. CT revealed two lesions in the brain. These lesions were removed surgically and were diagnosed histologically as CA. Familial CA of the CNS is relatively rare and the reported cases were 24 families consisted of 70 cases. We analyzed the reported cases to clarify the specificities of the familial cases. In the familial cases, CAs were apt to be multiple and were located more frequently in the posterior fossa than in the non-familial cases. In some familial cases, the vascular anomalies of the CNS other than CA or CA of the skin or retina were also revealed. Because of high incidence (89%) of the hemorrhage from the histologically verified CA, operation should be carried out even in the cases of CA with mild or no symptom, if the lesion is accessible surgically.
A case of hypothalamic astrocytoma with precocious puberty is presented. In July 1989, a 2-year-old girl was admitted to our hospital because of vaginal bleeding and enlargement of breasts. Breast development was Tanner's stage 3 and no pubic hair was present. Endocrinological evaluation revealed a slightly high level of LH, but the responses of LH and FSH to LH-RH test resulted in exceedingly high values similar to those in adults. Plain CT scan showed an isodense mass in the suprasellar cistern which was not enhanced following administration of contrast medium. MR imaging revealed the precise location of the mass attached to the posterior hypothalamus between the pituitary stalk and the mamillary bodies in sagittal view. The signal intensity of the mass was homogenous and isointense relative to the gray matter on T1 weighted image. But on T2 weighted image, it showed high signal intensity compared with the normal brain parenchyma. A right fronto-temporal craniotomy was performed and the tumor was partially removed. Histological examination disclosed moderate hypercellularity of glial cells but no neurons were visible. This appeared to be astrocytoma grade II. In the literature, CT and MRI behaviour of hypothalamic hamartomas are almost similar to our case. Therefore we think it is not possible at the present time to differentiate a low grade astrocytoma from hamartoma when using CT and MRI alone. In this case, the mechanism of development of precocious puberty seemed to be due to hypothalamic compression by the tumor.
We report a case of arachnoid cyst in the Sylvian fissure which progressed to uncal herniation. MRI was shown to be superior in visualizing uncal herniation.
Changes in blood-brain (BBB) permeability and local cerebral blood flow after intracarotid administration of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were examined quantitatively in rats with double-tracer autoradiography using [14C]alpha-amino-isobutyric acid and [18F]fluoroantipyrine. Forty-eight female Wistar rats were divided into four groups. The control group (Group 1) received 1 ml of 5% dextrose. The other three groups received three different doses of BCNU dissolved in 5% dextrose: Group II rats received 1 mg, Group III 3 mg, and Group IV 10 mg. The tracer study was performed on Day 1 or Days 4 to 12 after intracarotid administration of BCNU. In 11 rats in Group II, there were no changes of BBB permeability. Transient BBB permeability changes were seen in the striatum or hippocampus in 3 of the 5 rats (60%) in Group III within 24 hours. In 8 of 9 rats (89%) in the same group, late BBB permeability changes were observed in the hypothalamus with or without histological changes. BBB permeability changes were seen in all rats of Group IV. Focal increase of local cerebral blood flow on the infused side compared with the non-infused side of the brain was observed, although not at a significant level, in 5 of 25 rats examined with [18F]fluoroantipyrine. The results of BBB permeability and histological examinations and study of heterogenous distribution by [18F]fluorodeoxyglucose indicated that the ipsilateral subcortical structures such as the hypothalamus, amygdala, internal capsule, and caudate putamen have the highest incidence of neurotoxicity, which are closely related to histopathological damage seen in human BCNU leucoencephalopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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There have been few reports on the localization of S-100 protein positive chondrocytes in the human articular cartilages. We studied 59 articular cartilages of the aged subjects, 65 osteoarthritic (OA) and 39 rheumatoid arthritic (RA) articular cartilages, to detect the histological localization of S-100 protein using immunoperoxidase method (ABC). The results obtained from normal cartilages demonstrated strongly positive cells representing hypertrophic chondrocytes in the perivascular areas of the neonatal articular cartilage and in the deep zone of the infant articular cartilage. The moderately positive cells were found in the intermediate zone of infant and adult articular cartilages. In mild OA, there were many positive chondrocytes in the intermediate zone with erosion of the surface layer, while in moderate or severe OA many strongly positive cells were found in clusters. The hypertrophic cells in the metaplastic cartilage arising from bone marrow in subjects with severe OA, or from pannus after RA were also positive. It is therefore, suggested that S-100 protein may be correlated with the metabolic activity of the cartilage matrix such as collagen and proteoglycan, as reported in the literature. S-100 protein further, appears to be useful for evaluating histologically the activity of cartilage repair in the pathologic human articular cartilages.
To obtain information about the microheterogeneity of recombinant protein, recombinant eel growth hormone II (EGH) analogues expressed in Escherichia coli were isolated and characterized. The modification was classified into three types: monodeamidation of Asn, oxidation of Met and N-terminal formylation. Monodeamidated EGH was isolated by ion-exchange chromatography. The major deamidation site (Asn 147) was determined by peptide mapping using the substrate specificity of trypsin. Oxidized EGH and N-terminal-formylated EGH were isolated by reversed-phase high-performance liquid chromatography. Oxidized EGH was identified by amino acid composition analysis and N-terminal-formylated peptide by mass spectrometry.
A retrospective analysis was performed on 70 patients with malignant supratentrial astrocytic gliomas (astrocytoma Grade III or glioblastoma multiforme) treated with radiotherapy combined with vincristine (VCR), ACNU and PS-K. From January 1979 through December 1983, 27 patients were treated with treatment protocol A (group A). Protocol A was as follows: (1) total dose of 50 to 65 Gy radiation was given after surgery; (2) radiation plus combination VCR (0.02 mg/kg IV on 1st and 29th day of radiation) and ACNU (2 mg/kg IV 24 hrs after VCR) (3) after synchronized radiotherapy, ACNU (2 mg/kg IV every 6 or 8 weeks) and PS-K (3 or 6 g PO every day). Other 43 patients were treated with treatment protocol B (group B) from January 1984 through June 1988. Protocol B was as follows: (1) radiation dose was same as protocol A; (2) radiation plus combination VCR (0.02 mg/kg IV one day before radiotherapy) and ACNU (2 mg/kg IV on 1st and 1 mg/kg IV on 7, 21, 35th day, 1 hour before radiotherapy) (3) maintenance chemotherapy was same as protocol A. The difference between protocol A and protocol B was based on treatment schedule of ACNU. The characteristics of all patients were studied and identified, mainly age, histologic type, initial performance status, extent of tumor resection, maintenance chemotherapy. The reduction rate of tumor volume was 46.7% in the A group and 49.9% in the B group (not significant). The survival rates at 1, 2 and 3 years after surgery were 74.1%, 55.6% and 51.9% respectively for A group, and 80.5%, 42.4%, and 42.4%, respectively for B group.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood flow was measured in transplanted rat gliomas before and during a constant intravenous infusion of angiotensin II using hydrogen clearance methods. The brain tumor models were produced in syngeneic Wister-King-Aptekman male rats with stereotaxic inoculation of ethylnitrosourea-induced glioma cells (KEG-1). Induced hypertension up to 150 mmHg (mean arterial pressure) with the infusion of angiotensin II resulted in a significant increase of blood flow to tumor center compared to the normotensive state (p less than 0.001). Blood flow measured simultaneously in brain tissue of tumor-free contralateral hemisphere did not change. The therapeutic effect of administration of the simultaneous 1-(4-Amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and angiotensin II was evaluated in four experimental groups with the tumor-bearing rats. Twelve days after tumor implantation, the rats were administered angiotensin II to increase the mean arterial blood pressure to 150 mmHg, followed by intravenous injection of ACNU injection. The increased blood pressure was steadily maintained for 20 minutes. The ACNU/induced hypertension group showed a median survival time of 27.0 days, which was significant longer (p less than 0.02) than that of an ACNU treatment group (22.0 days), a hypertension treatment group (19.0 days), or a no treatment group (18.5 days). The enhanced therapeutic effect can be attributed to improving chemotherapeutic drug delivery due to increased blood flow in the tumor.
Skeletal muscle fibers from muscular dystrophic mice (C57BL/10-mdx) 1-4 months of age show elevated free Ca2+ concentrations both at resting and stimulated states, although contractility of adult (2-12 months old) mouse is similar to that of normal mouse. To evaluate the sensitivity of the contractile system of adult mdx mouse muscle to elevated free Ca2+ concentration, Mg2(+)-adenosine triphosphatase (ATPase) activity was examined using myosin, myosin B, and reconstituted actomyosin. Myosin Mg2(+)-ATPase activity of the mdx mouse was significantly higher than that of the normal mouse. Myosin B ATPase activity of the mdx mouse was also higher than that of normal mouse in free Ca2+ concentrations between 10(-9) and 10(-5) M, though there was no difference in the Ca2+ concentration required for half maximal activation of ATPase activity, 2 x 10(-7) M. Polymerized actin (FA) isolated from normal and mdx mice activated rabbit myosin Mg2(+)-ATPase identically, while activation of Mg2(+)-ATPase in mdx myosin by rabbit FA was significantly lower than that in normal mouse myosin. Rapid Pi liberation by Mg2(+)-ATPase in mdx mouse myosin was about half that of normal mouse myosin, being consistent with low activation of Mg2(+)-ATPase activity by rabbit FA. Polyacrylamide gel electrophoresis in the presence of pyrophosphate showed that myosin molecules of mdx and normal mice were both composed of three isozymes, although the fast migrating myosin isozyme (M1) was decreased while the slow migrating band (M3) was increased in mdx myosin. Subunit composition of myosin analyzed by polyacrylamide gel electrophoresis in the presence of SDS showed that the content of the smallest light chain (LC3) in mdx myosin was lower than that of normal mouse myosin, which agreed with findings that mdx myosin contained less M1 isozyme than normal myosin. These results indicated that the lowered response of mdx muscle fibers to elevated Ca2+ concentration can be attributed to the isozyme composition of myosin in mdx mouse.
The necessity, the methodology and clinical benefit of physical training were evaluated in 85 patients with valvular heart surgery. In 21 patients who had undergone the exercise stress test before surgery, corrective valvular surgery increased maximal oxygen uptake (max.VO2) from 15.4 before to 18.9 ml/min/kg, while 11 (52%) of them failed to increase exercise capacity over 5 METs. Of the total 85 patients, 41 (58%) again showed reduced exercise capacity in the initial postoperative stress test, suggesting that a return to work might be difficult without rehabilitation in these patients. We then compared two training programs: program A of short duration and frequent exercise and program B of longer duration and less frequent exercise, both using a bicycle exercise set at an intensity of 70% of the max.VO2. Both programs similarly increased max.VO2, while patients preferred program A, suggesting that exercise of longer duration could not be tolerated because of deconditioning. Program A was then prescribed to 62 patients, and it increased max.VO2 from 18.2 to 20.7 ml/min/kg after 4 weeks training without any complication. In 9 patients who served as controls undergoing no physical training, no spontaneous improvement in exercise capacity was observed. Of the 76 patients who received either program A or B, 28 patients failed to increase the max.VO2 by 10% or more. These patients presented atrial fibrillation, a cardiothoracic ratio greater than or equal to 60% or exercise-induced ST depression more frequently, suggesting that residual cardiac dysfunction might inhibit the training effects.(ABSTRACT TRUNCATED AT 250 WORDS)
A procedure for recording the electroretinogram (ERG) and the visual evoked potential (VEP) in freely moving cats was developed and used to test the visual toxicity of nalidixic acid. The electrodes for recording the ERG and VEP were implanted chronically in the sclera of the eye and on the surface of the visual cortex, respectively. Both the ERG and VEP were simultaneously recorded in freely moving cats using a slip ring that allows the cat to move freely without twisting the cables. After a 15-min dark-adaptation period, 20 responses to repetitive photic stimulation with an intensity of 2 joules and a 10-sec interstimulus interval were averaged by means of a minicomputer. The waveform of the ERG consisted of a negative wave (a-wave) followed by a positive wave (b-wave) with 2 to 3 oscillatory potentials on the rising slope. The VEP consisted of initial positive wave (P1 wave) followed by a negative wave (N1 wave) and late positive and negative deflections. The amplitude of the components of the ERG and VEP varied considerably from animal to animal, whereas within the same animal they were very stable. Using this technique, the effects of nalidixic acid, a retinotoxic compound, on the ERG and VEP were studied. Nalidixic acid produced a marked, but transient, decrease in the amplitude of the ERG b-wave after a single intravenous injection at a dose of 10 mg/kg. After repeated doses at 40 mg/kg/day for 2 weeks, the reduction in the amplitude of the b-wave was stronger, but remained transient. Upon ophthalmologic and histopathologic examination of the retina, no abnormalities indicating visual toxicity were observed. These results indicate that this procedure for recording the ERG and VEP is useful for evaluating the visual toxicity of drugs in freely moving cats.
The case of a 49-year-old female with a left parietal convexity meningioma associated with an acute subdural hematoma is described. She was admitted because of sudden onset of severe headache accompanied by nausea and vomiting. She was also confused, and 6 hours after admission she developed lethargy, right hemiplegia, and left mydriasis with no pupillary reaction to light. Computed tomography disclosed a round, extra-axial mass in the left parietal region; it was heterogeneously enhanced. Emergency craniotomy, performed after carotid angiography, revealed a tumor with a massive underlying subdural hematoma. The histological diagnosis was meningotheliomatous meningioma, and there were many meningothelial cells within the hematoma.