New antitumor substances, FR901463, FR901464 and FR901465. III. Structures of FR901463, FR901464 and FR901465.
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Antibiotics, Antineoplastic↗
Biomedical subjects
S Takase
Publications and source records attributed to S Takase.
["Associative" visual agnosia for objects, pictures, faces and letters with altitudinal hemianopia].
We report a 63-year-old right-handed man with the associative visual agnosia and bilateral altitudinal hemianopia. Neurological examination revealed fair visual acuity and normal ocular movement. Other cranial-nerve, motor, sensory, and autonomic functions were normal. The brain MRI showed multiple infarction involving the right fusiform and lingual gyri extending to the adjacent white matter of the occipito-temporal lobes and posterior part of the parahippocampus, the left fusiform and lingual gyri, and multiple lacunae in bilateral basal ganglia. Cerebral angiography demonstrated occlusion at the P1 portions of bilateral posterior cerebral arteries. 123I IMP-SPECT revealed decreased perfusion in bilateral occipital lobes, worse on the right. Visual evoked fields showed normal pattern of P100 m on bilateral occipital lobes. Neuropsychologically he was alert and oriented in place. In WAIS-R, he could not perform any of performance subtests, while his VIQ was 72. His verbal and visual memory was impaired. His visual perception of forms seemed to be almost preserved. He could copy simple drawing precisely, although he could not recognize the drawing just copied. He could match pictures, letters and photographs of faces. His visual identification of forms, on the other hand, was severely disturbed. He could identify only simple geometrical figures, but not simple drawings such as an apple or the face of his daughter. Reading Kanji was impaired and he read Kana in letter-by-letter manner. Tactile identification of objects was much better than visual one. Naming objects from verbal description was well preserved. Drawing fruits or cars from memory was intact. These data suggests that the present case had fairly good visual perception as was demonstrated by good copying and matching performance, and the case could be classified into the associative type of visual agnosia if the dichotomized classification of apperceptive and associative type is employed. However, closer look at his way of copying clearly showed that he copied in piecemeal fashion, suggesting difficulty in seeing a figure as a dynamic whole. It is possible that fine and precise discrimination of shape and pattern is subserved by the bilateral ventral or occipito-temporal visual system which was compromized in the present case.
Agnosia↗
Characteristics of serum hyaluronate concentrations in patients with alcoholic liver disease.
It has been reported that serum hyaluronate [hyaluronic acid (HA)] concentrations are increased in liver diseases, especially in alcoholic liver disease (ALD). However, the characteristics of serum HA concentration in patients with ALD have not been studied. In this study, first, we measured serum HA concentrations in patients with different stages of both ALD and non-ALD to clarify the characteristics of serum HA concentration in patients with ALD. Second, we measured serum HA concentrations in patients with ALD sequentially after abstinence. We also measured serum HA concentrations in patients with chronic type C hepatitis before and after treatment with interferon. Finally, we analyzed the relationship between serum HA concentrations and the contents of type IV collagen and laminin in the livers of both ALD and non-ALD patients. Serum HA concentrations in liver disease were higher than the cut-off value, and increased significantly (p < 0.001) in parallel with the progression of hepatic fibrosis in both ALD and non-ALD patients. Serum HA concentrations in patients actively drinking with ALD were significantly higher (p < 0.001) than those in non-ALD. After 4 weeks of abstinence, these concentrations fell to the levels of non-ALD. Although serum ALT levels were decreased in 80% of patients treated with interferon, serum HA concentrations were not changed or increased. A significant correlation between serum HA concentrations and hepatic type IV collagen and laminin content was present in ALD, but not in non-ALD. These results clearly suggest that the increase of serum HA concentrations in ALD may be associated with not only hepatic fibrosis, but also alcohol drinking.
Alcohol Drinking↗
Clinical significance of hepatitis GB virus C infection in alcoholic liver disease.
Recently, hepatitis GB virus C (HGBV-C) has been recovered from patients with non-A-E hepatitis. However, it has been unclear whether HGBV-C may be related to the development of alcoholic liver disease (ALD) or not. In this study, we determined HGBV-C RNA in sera from alcoholic patients without markers for hepatitis C and B viruses to evaluate the role of HGBV-C in ALD. Serum samples were obtained from 68 patients with ALD and 40 nonalcoholic patients with chronic type C liver disease. HGBV-C RNA was detected in only 3 of 68 (4.4%) patients with ALD, in 2 of 27 patients with hepatic fibrosis, and in 1 of 5 patients with chronic hepatitis. There was no HGBV-C RNA in sera from patients with fatty liver, alcoholic hepatitis, or cirrhosis. Serum levels of AST, ALT, and gamma-glutamyltranspeptidase in alcoholic patients with, as well as without, HGBV-C RNA decreased to normal levels after abstinence. In addition, an inflammatory change was not observed in liver biopsy specimens obtained from two HGBV-C-positive patients with alcoholic hepatic fibrosis. Our results clearly suggest that the prevalence of HGBV-C infection in patients with ALD is rare and that HGBV-C may not play an important role in the development of liver disease in alcoholics.
Alcohol Drinking↗
Relationship between perinatal appearance of cellular retinol-binding protein, type II and retinal reductase activity in chick liver.
To explore a role of the transiently appearing cellular retinol-binding protein, type II (CRBP(II)) in perinatal chick liver, we have examined whether the relationships exist among the perinatal changes in hepatic CRBP(II) protein and mRNA levels, retinal reductase activity and beta-carotene levels in liver and serum. Northern blot analysis for hepatic CRBP(II) revealed a transient expression of CRBP(II) mRNA around hatching. The protein of CRBP(II) was also expressed transiently and the highest levels of CRBP(II) were found in the livers 1-3 days after birth. The retinal reductase activity was very low at embryonic age, but its activity rapidly rose at hatching, peaking at 1 day after birth, followed by a gradual decrease to a lower level in 7-day-old chicks. This perinatal pattern of the retinal reductase activities was similar to the pattern of transient appearance of the hepatic CRBP(II), and was also paralleled to the developmental changes in serum and liver beta-carotene concentrations. These findings suggest that hepatic CRBP(II) transiently appearing during the perinatal period may involve in metabolizing hepatic beta-carotene, directing the retinal to the retinal reductase and leading further to the subsequent esterification of the converted retinol.
Alcohol Oxidoreductases↗
Maltitol increases transepithelial diffusional transfer of calcium in rat ileum.
We explored the mechanism whereby maltitol causes an increase of calcium absorption in the lower small intestine using everted ileal segments of rats. Under the calcium concentrations tested (1-20mM), which enabled us to assess the diffusional calcium transfer, maltitol in the mucosal-side medium (100mM) caused a 155% greater transepithelial calcium transfer as compared with the segments incubated without sugars. The maltitol-induced increment of calcium transfer was significantly higher than those elicited by glucose, sorbitol and maltose, and this increase was completely inhibited by W7, a calmodulin antagonist. Thus, our results suggest that maltitol might modulate the permeability of calcium through paracellular path, which possibly involves the activation of calmodulin.
Animals↗
Blood cyst with a calcium stone originating from the right atrial septum.
Blood cysts of the heart in adults are extremely rare, and their origin is usually from the valvular apparatus. However, a case was encountered of a blood cyst originating from the right atrial septum of a 59-year-old woman. Furthermore the cyst contained calcium stone. The cyst with the stone was Successfully excised. Neither situation has been reported previously in the literature.
Calcium↗
Effects of combination therapy with interferon and ofloxacin on chronic type C hepatitis: a pilot study.
Interferon is effective in only a limited number of patients with the 1b type of hepatitis C virus (HCV), indicating that a combination therapy with other antiviral drugs may be essential to obtain better results. In the present pilot study, the effects of a combination therapy with interferon (IFN) and an antibacterial drug, ofloxacin, were analysed. Ten patients with chronic type C hepatitis received the combination therapy (combination group). Six million units of natural IFN-alpha were administered daily for 3 weeks and then three times a week for 21 weeks. The combination therapy was initiated at the beginning of the eighth week of IFN treatment and 600 mg ofloxacin per day was administered for 12 weeks. As a control, changes in HCV-RNA were also analysed in patients who were treated with only IFN for the same period (IFN-alone group). In the combination group, serum transaminase levels and the titres of HCV decreased significantly with ofloxacin administration. Such changes were not observed in the IFN-alone group. The incidence of HCV-negativity at the end of ofloxacin administration of the combination group was significantly higher than in the IFN-alone group. The complete response rate was twice as high in the combination group as in the IFN-alone group. In two patients who did not respond well to the IFN-alone treatment, ofloxacin administration was commenced after the 24th week. Serum transaminase levels were normalized and HCV-RNA became negative in these two patients after the administration of ofloxacin. These results suggest that combination therapy with IFN and ofloxacin may be an effective treatment for chronic type C hepatitis.
Adult↗
Serum markers for hepatic fibrosis in alcoholic liver disease: which is the best marker, type III procollagen, type IV collagen, laminin, tissue inhibitor of metalloproteinase, or prolyl hydroxylase?
Although various serum markers for the evaluation of hepatic fibrosis have been introduced, it remains unclear which is the best marker to evaluate the hepatic fibrosis observed in alcoholic liver disease (ALD). In this study, we measured serum concentrations of the immunoreactive beta-subunit of prolyl hydroxylase, procollagen type III peptide, the 7S domain (7S-IV) and triple-helix domain (TH-IV) of type IV collagen, laminin, and tissue inhibitor of metalloproteinase (TIMP) in patients with and without ALD (non-ALD), and controls to evaluate the best serum marker reflecting the characteristic histologic features of ALD. After Azan-Mallory and silver-impregnated reticulin staining, histologic specimens were examined; and the degree of hepatic fibrosis was classified as mild, moderate, or severe. Although serum concentrations of all markers, except for TIMP, in patients with each type and stage of liver disease were higher than cut-off values and these concentrations increases with the progression of liver disease, statistical analyses indicate that serum TH-IV concentration is the best marker to distinguish ALD from non-ALD. A good correlation was also found between the hepatic type IV collagen content and serum TH-IV, but not serum 7S-IV concentration. Moreover, after abstinence from alcohol, serum concentrations of TH-IV decreased more quickly than other serum markers. These results clearly suggest that, compared with other markers, serum concentration of TH-IV may more strongly reflect the histologic features of ALD. However, other serum markers, except for TIMP, may be useful in evaluating the degree of hepatic fibrosis.
Alcohol Drinking↗
Acetaminophen metabolism in patients with different cytochrome P-4502E1 genotypes.
Cytochrome P-450 (CYP) 2E1 is the major ethanol-oxidizing enzyme of the nonalcohol dehydrogenase metabolic pathway in the liver. Recently, the presence of genetic polymorphisms of this enzyme was confirmed. In this study, to clarify the influence of CYP2E1 genotype on alcohol metabolism, we analyzed acetaminophen metabolism in subjects with different CYP2E1 genotypes. In normal subjects, a half-life of acetaminophen from blood was the longest in type A (c1/c1) and was the shortest in type C (c2/c2). The elimination rate in type C was more than twice that of type A and type B (c1/c2). In type A, both half-life and elimination rate of acetaminophen were not different between patients with noncirrhotic alcoholic liver disease within 1 week after abstinence and in normal subjects. In one patient with minimal change, there were no differences in both half-life and elimination rate within 1 and 6 weeks after abstinence. On the other hand, in type B, half-life was shorter and the elimination rate was greater in alcoholic noncirrhotic patients within 1 week after abstinence than in alcoholic patients with type A and in normal subjects with type B. In type B, half-lives were shorter, and the elimination rates were greater in patients with alcoholic liver disease within 1 week after abstinence than 4 to 6 weeks after abstinence. These results suggest the possibility that alcohol metabolism in individuals with the c2 gene may be greater than those with the c1 gene, and that the induction of CYP2E1 by ethanol in type B may occur more markedly than that in type A, although the sample number is too small to obtain final conclusions.
Acetaminophen↗
Lack of lecithin: retinol acyltransferase activity in chick lungs.
Our previous study revealed that no retinyl esters were detectable in chick and hen lungs, suggesting that the retinol esterification system may be absent in these tissues. This possibility encouraged us to investigate whether chick lungs exhibit the activity of a retinol esterifying enzyme, i.e., lecithin: retinol acyltransferase (LRAT). The LRAT activity was assayed with dilauroyl phosphatidylcholine and either complex of retinol-cellular retinol-binding protein, type two or retinol-cellular retinol-binding protein in microsomal preparations of lung, duodenum and liver of 7-day-old chicks. Relatively high levels of LRAT activity were present in the duodenum and the liver of chicks as well as in the rat lung. However, the chick lung exhibited no LRAT activity. The lungs of both rat and chick showed similar and low levels of acyl-CoA: retinol acyltransferase (ARAT) activity, but only rat lung, but not chick lung, contained a detectable amount of retinyl esters. Thus, the retinyl ester storage in the lung seems to depend on the presence of LRAT activity in the lung, but it is independent of the presence of ARAT activity in the lung. The absence of LRAT activity and retinyl esters in the chick lung suggests that the retinol in the chick lung may not be provided from retinyl ester storage, and the retinol transferred directly from serum should be utilized to generate retinoic acid.
Acyltransferases↗
New antitumor substances, FR901463, FR901464 and FR901465. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.
New antitumor substances, FR901463, FR901464 and FR901465 were isolated from the culture broth of a bacterium of Pseudomonas sp. No.2663. FR901463, FR901464 and FR901465 remarkably enhanced the transcriptional activity of the promoter of SV40 DNA virus. Further, these compounds exhibited potent antitumor activities against murine and human tumor cell lines in vitro.
Animals↗
[30-year progress of Japanese Medical Society of Alcohol and Drug Studies--present status and future of alcohol studies].
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Alcohol Dehydrogenase↗
[Immunoadsorption therapy for Fisher's syndrome: analysis of the recovery process of external ophthalmoplegia and the removal ability of anti-GQ1b antibodies].
The beneficial effect of plasma exchange, plasmapheresis or immunoadsorption therapy on Fisher's syndrome, suggested previously, has not been proved since no controlled studies have been conducted. In order to assess the effect of any treatment on Fisher's syndrome, simple and reasonable grading scales for evaluating the major neurological signs are needed. We tried immunoadsorption therapy in four patients with Fisher's syndrome, whose sera had anti-GQ1b antibodies. The clinical course was observed, with assessment of the severity of the major neurological signs based on grading scores; ranging from 0 to 30 for external ophthalmoplegia, from 0 to 10 for ataxia, and from 0 to 16 for areflexia. Tryptophan- or phenylalanine-linked polyvinyl alcohol gel column (TR-350, PH-350) was used as an adsorbent. In a patient who had IgG anti-GQ1b antibody and another patient who had both IgG and IgM anti-GQ1b antibodies, we compared the effectiveness of TR-350 and PH-350 to remove the anti-GQ1b antibody during the therapy. Two patients underwent immunoadsorption therapy at the height of clinical manifestations: in one patient, the therapy was discontinued because of critical hypotension and arrhythmia; the other was given only three sessions of therapy. The other two patients received six or seven sessions during the early recovering stage. All patients recovered without major neurological sequelae. Since ataxia was improved earlier than external ophthalmoplegia, the duration of hospitalization and the time of return to social life depended upon the recovery of external ophthalmoplegia. Analysis of the time course of external ophthalmoplegia score indicated that the improving period and the 50%-recovery day came earlier in the patients who were given a sufficient number of sessions than those who received an insufficient number of sessions. The treatment with TR-350 reduced the IgG anti-GQ1b antibody titer more than that with PH-350, but reduced the IgM anti-GQ1b antibody titer similarly. Immunoadsorption therapy using TR-350 has a probable beneficial effect on Fisher's syndrome even though it is carried out after the height of illness. The evaluation method for the severity of external ophthalmoplegia that we used in the present study is useful for assessing the effect of therapy on Fisher's syndrome.
Adult↗
[Transient prosopagnosia and lasting topographical disorientation after the total removal of a right occipital arteriovenous malformation].
A 32-year-old right-handed female tour guide developed a transient prosopagnosia after the total removal of an arteriovenous malformation in the right occipital lobe. Neurological examination revealed only a left homonymous hemianopsia. The ablation on the right side involved total occipital lobe, the posterior region of the parahippocampal gyrus, and a part of the precuneus and angular gyrus. Neuropsychologically she was alert and oriented in time and place. No aphasia or apraxia was observed. Visual recognition of objects, colors and letters was normal. She could match faces and insects easily, despite a close resemblance among them. Her prosopagnosia resolved in one month, while her impairment in topographical orientation and nonverbal memory continued more than eight months. These findings exclude the possibility that her prosopagnosia was derived from visual agnosia, poor discrimination of details, or nonverbal memory deficit. Excluding cases with malignant brain tumor which may affect more diffuse area of the brain, there was only one reported case who developed persistent prosopagnosia after the right occipital lobectomy. Given the rarity of prosopagnosics with only right-sided lesions, it seems that in most of humans posterior parts of both hemispheres participate in the identification of faces.
Adult↗
Investigation of genetic risk factors associated with alcoholism.
Alcoholism is a multifactorial disease influenced by genetic-environmental interaction. Genetic variation of the receptor may be associated with alcohol dependence due to its modified function in behavioral and physiological responses. In the present study, polymorphic alleles of cholecystokinin B receptor (CCKBR), serotonin 1A receptor (HT1AR) genes, and mitochondrial DNA were analyzed. DNAs were isolated from the blood samples of 112 healthy controls and 106 alcoholics. Genetic variation was detected by SSCP analysis, followed by direct sequencing of polymerase chain reaction product as well as restriction fragment-length polymorphism. Three different mutations were found in the exon 3 sequence of CCKBR: His (CAT) at aa207-->His (CAC) (5.4%), Arg (CGC) at aa215-->His (CAC) (4.5%), and Val (GTG) at aa138-->Met (ATG) (0.9%) in controls. Genotypic distribution of alcoholics was not significantly different with that in controls. A proline (CCG) to leucine (CTG) substitution at amino acid 16 of HT1AR was found in alcoholics (4.5%) and in controls (4.7%). This mutation site of HT1AR was different in comparison with the variants reported by Nakhai et al. (Biochem Biophys. Res. Commun. 210:530-536, 1995). Analysis of the mitochondrial DNA showed that a 491 bp deletion in the sequence of ATPase exists as heteroplasmy in 58% of alcoholics, but not in controls. Heteroplasmic deletion of mitochondrial DNA may be a useful marker for alcohol abuse. Further study is undergoing to elucidate the cause and significance of this deletion in alcoholics.
Alcoholism↗
[A 91-year-old man with a stroke, hypertension, and renal failure].
We report a 91-year-old man who had a stroke and died of renal failure. He had been treated for hypertension since 20 years before the onset of the present illness. In addition, he was operated on a gastric cancer 17 years previously. Otherwise he was doing well until May 29, 1991 (when he was 87-year-old) when he had sudden onset of dysarthria and right facial weakness. He was admitted to our hospital. On admission, general physical examination was unremarkable, and neurologic examination revealed a mentally sound man with slight dysarthria, right facial weakness, orolingual dyskinesia, and dysequilibrium in which he showed difficulty in tandem gait; however, no cerebellar ataxia was noted. A cranial CT scan revealed leukoaraiosis with multiple low density areas in the cerebral white matter. His BUN was 37 mg/dl and Cr 2.2 mg/dl. His neurologic symptoms cleared within the next few weeks and he was discharged with ticlopidine 100 mg q.d.. He had been doing well after the discharge except for gradual worsening of his renal function; his BUN was 65 mg/dl and Cr 3.27 mg/dl in April of 1994. On March 10, 1995, he fell down and hit his back; he became unable to walk because of pain, and he was admitted again on March 16, 1995. On admission, his blood pressure was 170/80 mmHg. There was an 1 + pitting pretibial edema; otherwise general physical examination was unremarkable. Neurologic examination revealed an alert and oriented man, however, Hasegawa's dementia scale was 23/30. Higher cerebral functions as well as cranial nerves were intact. He showed some unsteadiness of gait, however, no motor weakness or ataxia was noted. Deep tendon reflexes were diminished, but Chaddock sign was positive bilaterally. Vibration was diminished in the feet, however, pain and touch sensations were intact. Laboratory examination revealed a compression fracture of the twelfth thoracic vertebra. Blood count and chemistries were as follows; Hb 7.6 g/dl, Hct 23.3%, TP 6.0 g/dl, Alb 3.6 g/dl, BUN 87 mg/dl, Cr 4.53 mg/dl, T-Chol 174 mg/dl, HDL-Chol 49 mg/dl, Glu 156 mg/dl, Na 142 mEq/L, K 5.4 mEq/L, Cl 115 mEq/L. A urine specimen contained 1 + protein and 1 + glucose, and the sediments contained hyaline casts. A cranial CT scan was essentially same as that taken four years ago. His hospital course was complicated with pneumonia, congestive heart failure, and progressive renal failure. He was treated with intravenous fluid, chemotherapy, and other supportive measures, however, he expired from respiratory failure on April 30, 1995. He was discussed in a neurologic CPC, and the chief discussant arrived at the conclusion that the patient had Binswanger's disease in the brain, benign nephrosclerosis from arteriolosclerosis due to hypertension, congestive heart failure, and pneumonia. Opinions were divided regarding the question as to whether or not this patient had Binswanger's disease. Although his cranial CT scan revealed leukoaraiosis, his dementia and gait disturbance was only mild until his fall on March, 1995. Clinical features did not conform to those of Binswanger's disease. Postmortem examination of the right hemisphere revealed wide spread atherosclerosis and arteriolosclerosis. The kidney showed benign nephrosclerosis due to arteriolosclerosis. Sclerotic changes were also seen in the coronary arteries and the left middle cerebral artery with 70% stenosis. Myelin stain showed diffuse myelin pallor of the cerebral white matters with scattered small infarcts. Arterioles in the white matter showed arteriolosclerosis. Small infarcts were also seen in the putamen and in the thalamus. This patient appeared to have had circulatory disturbance of the white matter which is the basic abnormality causing Binswanger's disease. However, white matter changes in this patient were not quite severe enough to make a pathologic diagnosis of Binswanger's disease.
Aged↗
Decrease in cerebellin and corticotropin-releasing hormone in the cerebellum of olivopontocerebellar atrophy and Shy-Drager syndrome.
Four neuropeptides; cerebellin, corticotropin-releasing hormone (CRH), neuropeptide Y and somatostatin were studied by radioimmunoassay in the postmortem human brains obtained from three patients with olivopontocerebellar atrophy (OPCA) and one with Shy-Drager syndrome. Significant decreases in cerebellin and CRH concentrations were found in the cerebellar hemisphere of these diseases compared with controls. These findings suggest important pathophysiological roles of cerebellin and CRH in these cerebellar diseases. Such significant decreases were not found in neuropeptide Y and somatostatin.
Adult↗