Biomedical subjects
Publications and source records attributed to H Uno.
The metabolites 3 and 4 of 2-(4-ethyl-1-piperazinyl)-4-phenylquinoline dimaleate (AS-2646, 1), a candidate as a gastric antisecretory and antiulcer drug, were synthesized to confirm the proposed structures. The effects of the metabolites 2-4 on ulcer induced by stress were determined.
A new series of 3-heteroarylacrylamides 2 and 4 was prepared and the inhibitory activities against the rat passive cutaneous anaphylaxis (PCA) reaction and the enzyme 5-lipoxygenase (5-LO) were tested. Most of the compounds exhibited an anti-PCA activity superior to or equivalent to ketotifen and had a 5-LO inhibitory activity. The 3-heteroarylacrylamide derivatives including 3-(3-pyridyl)acrylamides represent a new structural class of compound that exhibits not only an in vivo anti-PCA activity but also an in vitro 5-LO inhibitory activity.
Natural killer (NK) activity of peripheral mononuclear cells (PMNC) from patients with adult T-cell leukemia (ATL), anti-HTLV-I antibody positive healthy carriers, and anti-HTLV-I antibody negative healthy persons (Ab-negative persons) was investigated using various target cells. PMNC from patients with ATL and healthy carriers had reduced NK activity against the NK-sensitive non-HTLV-I producing target cells, compared with the controls. In contrast, PMNC from patients with ATL, healthy carriers, and Ab-negative persons did not exhibit significant NK cell lysis against HTLV-I producing cells. However, one Ab-negative person exhibited increased NK cell lysis against an HTLV-I producing target cell. The effector cells involved in this enhanced cytolysis were found to be CD3+, HNK-1+, and CD8+. HTLV-I producing cells were lysed by PMNC from Ab-negative persons in the presence of anti-HTLV-I antibody (antibody-dependent cellular cytotoxicity; ADCC). The efficiency did not show significant difference between antibodies from patients with ATL and those from healthy carriers. The ADCC was specific to HTLV-I producing cells. PMNC from one patient with ATL in remission exhibited increased ADCC in the presence of autologous serum against HTLV-I, whereas PMNC from a patient with ATL or a healthy carrier did not exhibit ADCC. These results indicated that NK and K cells influence the immunological surveillance against HTLV-I infection or leukemic cells.
Sustained exposure to glucocorticoids (GCs), adrenal hormones secreted during stress, can cause neural degeneration in the rat. This is particularly so in the hippocampus, a principal neural target site for GCs, in which GCs can exacerbate the rate of neuron death during normal aging, as well as the severity of neuronal damage after various neurological insults. Thus, stress can be a potent modulator of hippocampal degeneration in the rat. The present report suggests a similar association in the primate. Eight vervet monkeys, housed in a primate center in Kenya, that had died spontaneously from 1984 to 1986, were found at necropsy to have multiple gastric ulcers; a retrospective, neuropathological study was then done of this opportunistic population. Compared with controls euthanized for other research purposes, ulcerated monkeys had marked hippocampal degeneration that was apparent both quantitatively and qualitatively, and both ultrastructurally and on the light-microscopic level. Minimal damage occurred outside the hippocampus. Damage was unlikely to have been due to an agonal or post-mortem artifact. Instead, ulcerated monkeys appear to have been subject to sustained social stress, perhaps in the form of social subordinance in captive breeding groups: most came from social groups, had significantly high incidences of bite wounds at necropsy, and had hyperplastic adrenal cortices, indicative of sustained GC release. Moreover, the specific hippocampal cell fields damaged in ulcerated animals matched those damaged by GCs in the rodent hippocampus. Thus, this represents the first evidence suggesting that sustained stress, via GC hypersecretion, might be neurodegenerative in the primate.
Thirty-two patients with advanced bladder cancer received intraarterial infusion of chemotherapy with cis-platin (CDDP). For twenty-one patients, the intraarterial infusion was carried out using Seldinger's method. On the other hand, for the eleven patients who were diagnosed as inoperable cases, the intraarterial infusion was carried out using the reservoir system. The mean regression in the size of the tumor was 64%, which was statistically superior to the mean regression in the intravenous administration group, was 45%. According to Shimosato's criteria, the pathological response was evaluated. Seven patients (22%) were detected as having more than grade III. On the other hand, among the intravenous administration group, only one case (11%) was detected as more than grade III. Following the intraarterial infusion of chemotherapy, subsequent surgical treatment was performed on 21 patients. Fourteen patients underwent the organ-preserving operation, either transurethral resection or segmental resection of the bladder, and seven patients underwent radical cystectomy. In seventeen patients (53%), there was no evidence of the disease. Especially, eleven patients (79%) who under went the organ-preserving operation had no evidence of the disease. The intraarterial infusion method of chemotherapy with CDDP showed a high response, both in terms of regression of tumor size and the pathological degeneration, compared to intravenous administration of CDDP. The subsequent surgical treatment following chemotherapy issues not only a better survival rate, but also makes possible preservation of organs.
Biochemical properties of a cytosolic protein-tyrosine kinase (CPTK-40) partially purified from porcine spleen were characterized and compared with p40 kinase, a cytosolic protein-tyrosine kinase from bovine thymus. When CPTK-40 was incubated with MnCl2 and (gamma-32P)ATP, only a phosphoprotein with a molecular weight of 40 kilodalton was observed. CPTK-40 efficiently phosphorylated tubulin with the rate of 0.5 nmol/min/mg. Unlike p40 kinase, casein was also a substrate for CPTK-40. Among various divalent cations tested, Co2+, Mn2+ and Mg2+ were effective metal ions for the enzyme activity. Ca2+ could also serve as a divalent cation for the activity although the rate was low. These results suggest that CPTK-40 is similar but not identical to p40 kinase.
Benign and malignant lesions from monkeys were analyzed for the presence of papillomavirus (PV) DNA. By hybridization with different PV DNA probes under conditions of lowered stringency, two tumors were found to contain PV-specific DNA sequences: (1) a cutaneous papilloma from a Colobus monkey; and, (2) a lymph node metastasis of a squamous cell carcinoma of the penis from a Rhesus monkey. Analysis of the DNA of the papilloma from the Colobus monkey indicated the presence of extrachromosomal DNA whereas analysis of DNA from the Rhesus tumor suggested the presence of integrated viral DNA. The physical size (7.8 and 8.1 kb), colinear alignment to HPV-5, and cross-hybridization with other PV types under low stringency indicate that the two genomic DNA clones represent new PV types that have been tentatively designated as Rhesus papillomavirus type 1 (RhPV 1) and Colobus guereza papillomavirus type 2 (CgPV 2). A putative viral-host DNA junction fragment was also isolated from the Rhesus genomic library. Nucleotide sequences very closely related to RhPV 1 were observed by in situ hybridization in a laryngeal carcinoma from the Colobus guereza monkey. This report communicates the finding of novel papillomaviruses associated with a benign cutaneous tumor and genital and laryngeal malignancies in non-human primates which may have significance as a putative system for the study of papillomavirus-induced genital and laryngeal malignancies in humans.
1. Pharmacological properties of a new centrally acting muscle relaxant (NC-1200) were tested in isolated muscle preparations. 2. NC-1200 acted as a Ca-blocker in the guinea pig taenia caecum. The pA2-value was 5.67. 3. In the rabbit aorta, NC-1200 competed with serotonin at serotonin receptors and also shifted the concentration response curves of histamine and norepinephrine suggesting the possibility that NC-1200 interacted with histamine and norepinephrine receptors. The pA2-value of NC-1200 against serotonin was 6.02. 4. There was no evidence that NC-1200 interacted with drug-receptors in the muscles except the rabbit aorta. 5. The present results are similar to the previous findings that the properties of serotonin, histamine and norepinephrine receptors in the rabbit aorta were different from those in other muscles.
A series of 3-phenyl-2-piperazinyl-5H-1-benzazepines and related compounds were synthesized and evaluated for potential neuroleptic activity. The preparation of these compounds was carried out by 2,3-dichlorination of 3-phenyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-ones with phosphorus pentachloride followed by amination and concurrent dehydrochlorination. Compounds having the 4-chloro or 4-fluoro substituent in the 3-phenyl group were found to possess the neuroleptic-like activity. Among them, 2-(4-methyl-1-piperazinyl)-3-(4-fluorophenyl)-5H-1-benzazepine dihydrochloride (23) was comparable to chlorpromazine in inhibiting exploratory activity, conditioned avoidance response, and self-stimulation response and more potent than chlorpromazine in antagonizing apomorphine-induced emesis. These neuroleptic effects may be based on an antidopaminergic property of the compound. In causing catalepsy or ptosis, however, 23 was weaker than chlorpromazine. Therefore, this ring system is of interest as a novel class of neuroleptics. Some compounds having the 7-chloro or 7-bromo substituent showed potent anticonvulsant effects against maximal seizures induced by electroshock or pentylenetetrazole.
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HLA antigens of patients with adult T cell leukaemia (ATL), T cell malignant lymphoma (T-ML), and healthy carriers of human T cell leukaemia virus type I (HTLV-I) were investigated in an endemic area of ATL in Japan. Sixty-two patients with ATL were subdivided into three groups based on their clinical features, including two unclassified patients; 36 acute type, 10 chronic type, and 14 smouldering type. The frequency of HLA-Bw62 was significantly increased in acute ATL, compared with control (Pc less than 0.0002). Increased frequency of HLA-DQw3 was observed in patients with ATL, T-ML positive for the antibody to HTLV-I (Ab-positive), and Ab-positive healthy carriers, compared with control (Pc less than 0.001, Pc less than 0.01 and Pc less than 0.0001, respectively). In addition, class I HLA antigens of peripheral lymphocytes of patients with ATL, especially acute ATL, showed altered expression, either extra antigens or decreased antigens. Analysis of 21 families, where more than two members were Ab-positive, showed that there was no linkage between the HLA complex and susceptibility to the virus infection. In 44 couples, in which either or both spouses were Ab-positive, no association with class I HLA antigens was found in either Ab-positive spouses or Ab-negative spouses. These findings might indicate that one class II HLA-linked gene controlled susceptibility to HTLV-I infection, and another class I HLA-linked gene exerted an influence on the clinical course of ATL.
A 45-year-old female visited our Department on February 7, 1986, with the principal complaint of swelling in the right upper abdomen. She was hospitalized on February 20. Ultrasonography, DIP, CT and right renal arteriography were performed. On March 10, the right kidney was extirpated transabdominally. The extirpated kidney weighed 1.2 kg and tightly adhered to the renal capsule. The kidney included a solid, yellowish white, homogeneous tumor. There was also a cyst outside of the tumor. The tumor was limited within, and easily separated from, Gerota's fascia. Pathological diagnosis revealed that the tumor was a leiomyoblastoma originated from the blood vessel. On March 26, postoperative VAC therapy (1 mg vincristine; 300 mg cyclophosphamide; 2 mg actinomycin D) was performed, and the patient was released from the hospital on April 8. As of August of 1987, no relapse of the disease has been detected. There have been very few reports of leiomyoblastoma in Japan. Whether leiomyoblastoma might take a malignant course was investigated to some extent on the basis of the reported literature.
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A 3 2/12-year-old boy had recurrent seizures, chronic respiratory infection, and delayed physical and mental development. He also had low plasma copper content typical of Menkes syndrome. Autopsy showed marked neuronal loss and gliosis in most areas of the cerebral and cerebellar cortices, midbrain, pons, and medulla. The spinal cord showed severe demyelination in both ascending (spinocerebellar) and descending (lateral corticospinal) tracts from the cervical to the sacral level. In addition to these neuronal lesions, both the meningeal and parenchymal arterial and venous branches were remarkably dilated in the brain and spinal cord. Our previous study of this case showed abnormal perivascular innervation and abnormal axonal swelling of the postganglionic adrenergic fibers elsewhere in the body. The metabolic disorder caused by copper deficiency induces severe neuronal degeneration that is apparently exaggerated by extensive and progressive vascular abnormality.
At various gestational periods, caffeine was injected intra-arterially or intraperitoneally into pregnant rats. The teratogenic effects of caffeine on the fetal heart were dose dependent and detectable at relatively low concentrations. The most susceptible stage was during septation of the heart. The most common cardiovascular malformation was ventricular septal defect. Extracardiovascular anomalies, such as decreased thymic weight and degeneration of the lens, were found in all fetuses; skeletal malformations were found in some fetuses.
Single cell responses to electrical stimuli applied to the optic chiasm and to the lateral geniculate nucleus were studied in expanded projection to the ipsilateral superior colliculus of neonatally enucleated and congenitally monocular rats. In both types of rats latencies to the afferent volleys were longer, and the latency correlation between the optic chiasm and the lateral geniculate responses was lower in the ipsilateral than in the contralateral superior colliculus cells. This was interpreted to suggest abnormal convergence of retinal axons with different conduction velocities in the ipsilateral retinocollicular projection. The deviation of ipsilateral superior colliculus cells from the high-latency correlation of the contralateral cells was more marked in congenitally monocular than in neonatally enucleated rats.