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Biomedical subjects

K Ono

Publications and source records attributed to K Ono.

At least 469 records · Page 26Linked to original sources

Adult T-cell leukaemia/lymphoma with multiple integrations of human T-cell lymphotropic virus type I proviral DNA: differing clinical features are linked to varied proviral integration.

Multiple integrations of human T-cell lymphotropic virus type I (HTLV-I) proviral DNA are occasionally found in tumor cells from patients with adult T-cell leukaemia/lymphoma (ATL). However, the clinical implications of multiple integrations of HTLV-I in ATL have not been well established. We studied 95 patients with ATL to elucidate the relationship between the multiple integrations of HTLV-I and the clinical characteristics. The proviral DNA of HTLV-I was examined by standard Southern blot analysis using the probe of an entire HTLV-I genome and the endonucleases with or without cleavage sites within the provirus. Multiple integrations of HTLV-I were detected in eight patients as extraordinary multiple bands; five patients showed multiple bands of the same intensity, and the remaining three showed multiple bands of differing intensities. The patients were divided into two groups based on these band patterns. One group was considered to exhibit one tumour cell clone carrying multiple copies of the provirus, whereas the other was considered to exhibit multiple tumour cell clones, each carrying one copy of the provirus. The former group of patients manifested a highly aggressive clinical course with frequent peculiar organ infiltrations, including the retina, uvea and muscle, along with the presence of large peripheral leukaemic T cells having flower-like nuclei. The latter group demonstrated an indolent clinical course with skin lesions or small leukaemic T cells having cleaved or lobulated nuclei. These findings suggest that the pattern of multiple HTLV-integrations into the tumor cell(s) has clinical implications in ATL. This may help to explain the heterogeneity of this disease.

Adult↗

Clinical usefulness of determining the rate of thermal clearance within heated tumors.

Between June 1987 and June 1988, 28 patients (28 tumors) with liver, retroperitoneal, intrapelvic, or superficial tumors were treated with hyperthermia combined with radiotherapy and/or chemotherapy. Hyperthermia was administered once or twice a week for 30-60 min per session, up to a total of 2-11 sessions, with an 8-MHz RF capacitive heating device. Blood flow in the tumors was evaluated from the rate of thermal clearance (TCR) using the bio-heat transfer equation. The TCR was measured in the middle of the first heating session and at the end of the last heating session by turning off the output power of the heating device. For 9 patients, contrast-enhanced CT scans were taken and CT numbers at the centers of tumors were measured before and after the entire course of hyperthermia. Changes in TCR were closely related to average tumor center temperature, changes in CT number, and tumor response. When smaller and more superficial tumors were treated by hyperthermia combined with radiotherapy and/or chemotherapy that consisted of many heating sessions and during which a high average tumor center temperature was achieved, a better tumor response was obtained. The better the tumor response, the higher the local control rate became. The cause-specific survival rate of patients who achieved good tumor responses was higher than that of patients who showed poor tumor responses. Changes in TCR and CT number in heated tumors were useful and important indicators of tumor response to hyperthermia.

Adolescent↗

Relationship between cell-killing efficiency and number of platinum atoms binding to DNA, RNA, and protein molecules in HeLa cells treated with cis-diamine(glycolato)platinum(II).

HeLa S-3 cells were treated with 195m Pt-radiolabeled cis-diamine(glycolato)platinum(II) (254-S) under various conditions, and the relationship between the lethal effect and the numbers of Pt atoms binding to DNA, RNA, and proteins was examined. The mean lethal concentrations for the cells treated with 254-S at 37 degrees C for 0.5, 1, 2, and 3 h were 67.1, 47.0, 26.8 and 8.1 microM, respectively. Using identically treated cells, we determined the numbers of Pt atoms combined with DNA, RNA, and protein molecules after fractionation of the cells. In this way, the D 0 values (D 0, the dose that causes an average of one lethal event per member of the population), expressed as the drug concentration, could be related to the number of Pt atoms combined with each fraction. The efficiency of the Pt atom in killing the cells, expressed as the reciprocal of the D 0 values, was then calculated for each fraction. The results suggested that DNA was the primary target for cell killing by 254-S. The target volumes for DNA were 3.96, 4.97, and 11.77 x 10(4) nucleotides for 1-, 2-, and 3-h treated cells, respectively. In terms of the target volume, the cell-killing effects of 254-S were comparable to those of cis-diamine-dichloroplatinum(II) (CDDP), for which the target volumes under identical conditions were determined to be 5.17, 5.71, and 10.3x10 4 nucleotides, respectively, while in terms of the mean lethal dose (D 0), the cell-killing effects of 254-S were lower than those of CDDP by a factor of 5.1 (47.0/9.3), 4.0 (26.8/6.7), or 2.5 (8.1/3.2) for 1-, 2-, or 3-h treatment, respectively.

Antineoplastic Agents↗

Sensitive plaque assay and propagation of Chuzan (Kasba) virus, a Palyam serogroup orbivirus, in BHK-21 cells.

Various factors influencing plaque formation of Chuzan virus in BHK-21 cell monolayers were studied and a practical method for plaque assay was developed. On addition of trypsin (5 micrograms/ml) and/or diethylaminoethyl (DEAE)-dextran (50 micrograms/ml) to the virus diluent as the virus adsorption medium and agar overlay medium, the number of plaques increased. When 100 micrograms/ ml DEAE-dextran was added to the diluent and overlay medium, plaques were produced in about 10-fold higher numbers than without trypsin and DEAE-dextran. Based on these results, a practical plaque assay method for Chuzan virus was established. Using this method, one-step growth of Chuzan virus was performed at an input multiplicity of 25 plaque-forming units (PFU) per cell. Cytopathic effects were first observed at 7.5 h post-inoculation (p.i.), and were complete at 12 h p.i. The titre of cell-associated virus, after gradual decline during the first 3 h of incubation, showed a rise within 4.5 h p.i. and a rise to a plateau of 10(6.3)PFU/0.2 ml at 12 h p.i. By indirect immunofluorescence, virus-specific antigen was detected in the cytoplasm of the cells at 4.5 h p.i., and all the cells fluoresced at 6 h p.i. Haemagglutination activity was first detected in infected whole cultures at 7.5 h p.i. reaching a plateau of 1:64 at 15 h p.i. Plaque formation and haemagglutination by the virus were specifically inhibited by antisera against the original and the plaque-cloned virus.

Animals↗

Primary adenocarcinoma of the renal pelvis with special reference to histochemical observations.

A case of adenocarcinoma of the renal pelvis is presented. The patient was an 84-year-old man suffering from long-standing right-sided nephrolithiasis. Surgical resection of the right kidney revealed adenocarcinoma with slight stromal invasion. A tubulovillous adenoma, which was morphologically similar to an adenoma of the large intestine, was also found adjacent to the adenocarcinoma. The pelvic epithelium neighboring the lesion revealed intestinal metaplasia. Histochemical studies revealed that the tumor in the patient and adenocarcinomas or adenomas of the large intestine have similar properties of cytoplasmic mucin. These findings suggest that the epithelium with intestinal metaplasia may have developed into the adenoma and finally transformed into the adenocarcinoma. In addition, only tumor cells with severe atypia, most of which morphologically corresponded to adenocarcinoma, demonstrated positive nuclear staining for anti-p53. This suggests that p53 may play an important role in the malignant transformation of adenomas into adenocarcinomas, as is the case in the large intestine.

Adenocarcinoma↗

Biological responses to administered interferon in alcoholics.

To elucidate the influence of chronic alcohol intake on interferon (IFN) therapy in patients with various diseases, 3 million units of natural IFN (nHuIFN-alpha Ly) was administered once to alcoholics, nonalcoholic chronic hepatitis C (CH-C) patients, and healthy subjects. The serial changes of serum activity of 2'-5' oligoadenylate synthetase, serum levels of beta 2-microglobulin, C-reactive protein (CRP), and body temperature were monitored. The increase in the activity of 2'-5' oligoadenylate synthetase, the response of serum-reactive protein, and body temperature after IFN administration were significantly lower in the alcoholics than those in CH-C group, and healthy subjects (control group). The serum beta 2-microglobulin level was already higher in the alcoholics before IFN administration than those of the control group and the CH-C group. These findings suggest that physiological responses to exogenous IFN in alcoholics are generally decreased. Hence, for the maximum effect of IFN therapy, it is important for patients to abstain from alcohol intake and for doctors to carefully consider the timing of initiation.

2',5'-Oligoadenylate Synthetase↗

Perforated patch-clamp recording in cardiac myocytes using cation-selective ionophore gramicidin.

Whole cell currents were recorded in single myocytes dissociated from guinea pig ventricles by the patch-clamp technique. The addition of 0.1 mg/ml gramicidin D, a cation-selective ionophore, into the pipette solution induced a gradual spontaneous perforation of the patch membrane under a conventional cell-attached configuration. The access resistance, measured at approximately 12 min after formation of a gigaohm seal, was 9.2 +/- 1.5 M omega (n = 12). The perforated patch membrane exhibited ionic selectivity for various monovalent cations, with a relative order of Cs+ (1.11) > K+ (1.0) > Na+ (0.65) >> tris(hydroxymethyl)aminomethane+ (approximately 0) but was not permeable for Cl-. Under the gramicidin-perforated patch recording configuration, the cells showed the typical electrophysiological properties for ventricular cells reported previously. The intracellular Cl- concentration, estimated from the reversal potential of the catecholamine-induced Cl- current, was 36.3 +/- 2.9 mM (n = 17). We thus conclude that the gramicidin-perforated patch recording mode provides a useful tool for recording the ionic currents while maintaining the intracellular Cl- concentration.

Action Potentials↗

Hyperreninemia, hypertension, and congestive heart failure in focal interstitial nephritis.

Hyperreninemia probably due to focal interstitial nephritis of the right kidney caused an acute onset of hypertension and cardiac dysfunction including valvular insufficiency in a 5-year-old boy. This congestive heart failure in association with valvular insufficiency and hypertension was dramatically improved following right nephrectomy. Abruptly activated renin-angiotensin II may lead to congestive heart failure and valvular dysfunction without myocardial hypertrophy in a young heart.

Aortic Valve Insufficiency↗

New hydrolyzable tannins, shephagenins A and B, from Shepherdia argentea as HIV-1 reverse transcriptase inhibitors.

Two new hydrolyzable tannins, shephagenins A and B, were isolated along with hippophaenin A and strictinin from the leaf extract of Shepherdia argentea, which showed a remarkable inhibitory activity against human immunodeficiency virus (HIV)-1 reverse transcriptase. Their structures, having a gluconic acid core, have been elucidated on the basis of spectroscopic and chemical methods. The inhibitory effect of the leaf extract on HIV-1 reverse transcriptase was found to be due to tannins, and their activities were stronger than that of (-)-epigallocatechin gallate as a positive control.

Antiviral Agents↗

Effects of depletion of T cell subpopulations on the course of infection and anti-parasite delayed type hypersensitivity response in mice infected with Babesia microti and Babesia rodhaini.

To elucidate the role of T cell subpopulations in the protective cell-mediated immune response at the initial phase of infection with Babesia microti (BM) and B. rodhaini (BR), the changes in the course of infection and anti-parasite delayed type hypersensitivity (DTH) response after BM or BR inoculation were investigated in Lyt-2+ T cell or L3T4+ T cell-depleted mice. Depletion of Lyt-2+ T cells strongly enhanced the resistance to BM infection, whereas it increased the susceptibility to BR infection. In contrast, depletion of L3T4+ T cells increased susceptibility to BM infection, while it enhanced resistance to BR infection. The anti-parasite DTH response in BM-infected mice was significantly enhanced by depletion of Lyt-2+ T cells, while significantly reduced by depletion of L3T4+ T cells. No effects of depletion of either Lyt-2+ or L3T4+ cells on DTH response was observed in BR-infected mice. From these results, it was suggested that the roles of Lyt-2+ and L3T4+ T cells in the protective cell-mediated immune response at the initial phase of infection were different between BM- and BR-infected mice, resulting in the difference in their course of infection.

Animals↗

Neurons with perineuronal sulfated proteoglycans in the mouse brain and spinal cord: their distribution and reactions to lectin Vicia villosa agglutinin and Golgi's silver nitrate.

This study demonstrates that many neurons in the somatosensory cortex, cingulate cortex, retrosplenial cortex and hippocampal subiculum of the mouse brain are covered by sulfated proteoglycans which are intensely negative-charged and stained with cationic iron colloid, while being digested with hyaluronidase. Neurons with similar perineuronal proteoglycans are also recognized in the extrapyramidal system (superior colliculus, red nucleus, reticular formation, vestibular nuclei and cerebellar nuclei), in the secondary auditory system (cochlear nuclei, nucleus of trapezoid body, inferior colliculus and nucleus of lateral lemniscus), in the vestibulo-ocular reflex system (vestibular nuclei and extraocular motor nuclei), and in the pupillary reflex system. The neurons with perineuronal sulfated proteoglycans in the cerebral cortices and hippocampal subiculum are usually labeled with the lectin Vicia villosa agglutinin, though those in the cerebellar, vestibular and cochlear nuclei may not be reactive to this lectin. Double staining of the retrosplenial cortex, hippocampal subiculum and cerebellar nuclei with Golgi's silver nitrate and cationic iron colloid indicates that the perineuronal sulfated proteoglycans are identical with the Golgi's reticular coating or glial nets.

Animals↗

Cone-associated c-fos gene expression in the light-damaged rat retina.

PURPOSE: To examine whether light-controlled c-fos gene expression is mediated by a cone specific pathway in the rat retina. METHODS: To produce a cone-rich retina, rats were placed under continuous lighting for 21 days. The illuminance in the cages ranged from 1200 to 2000 lux. The presence of cones was determined by peanut agglutinin and rods by the monoclonal antibody 1-E7. The presence of c-fos transcripts in the retinas was analyzed by in situ hybridization using single-stranded RNA probes. RESULTS: After long-term exposure to continuous light, the 1-E7 immunoreactivity was not detected in the outer nuclear layer. The cone photoreceptors and cells in the ganglion cell (GCL) and inner nuclear layers (INL) survived. In normal retinas, there was strong hybridization for c-fos expression in the GCL and the INL 30 minutes after the onset of the light cycle. Light-damaged retinas also showed hybridization in the GCL but not in the INL under the same light regime. CONCLUSIONS: These results suggest that c-fos gene expression can be controlled through a cone specific pathway in the retina.

Animals↗

[A case of advanced gastric cancer with lung and liver metastasis treated by CDDP and 5-FU].

A 62-year-old man suffering from advanced gastric cancer with multiple lung and liver metastasis was treated with FP (CDDP . 5-FU) therapy. As a result, lung metastasis disappeared completely and liver metastasis was significantly reduced in size (93%). Then, total gastrectomy, splenectomy and micro-wave-coagulation of the liver tumors were performed. Therefore, it can be said that FP therapy is an effective neoadjuvant chemotherapy.

Adenocarcinoma↗

The cervical spine in athetoid cerebral palsy. A radiological study of 180 patients.

We have reviewed the cervical spine radiographs of 180 patients with athetoid cerebral palsy and compared them with those of 417 control subjects. Disc degeneration occurred earlier and progressed more rapidly in the patients, with advanced disc degeneration in 51%, eight times the frequency in normal subjects. At the C3/4 and C4/5 levels, there was listhetic instability in 17% and 27% of the patients, respectively, again six and eight times more frequently than in the control subjects. Angular instability was seen, particularly at the C3/4, C4/5 and C5/6 levels. We found a significantly higher incidence of narrowing of the cervical canal in the patients, notably at the C4 and C5 levels, where the average was 14.4 mm in the patients and 16.4 mm in normal subjects. The combination of disc degeneration and listhetic instability with a narrow canal predisposes these patients to relatively rapid progression to a devastating neurological deficit.

Adolescent↗

[Comparative study on serological diagnosis of entamoebiasis histolytica].

The practicability of four diagnostic methods for entamoebiasis histolytica including micro-gel diffusion precipitin test (MGDP), indirect immunofluorescent antibody test (IFA), indirect hemagglutination test (IHA) and enzyme-linked immunosorbent assay (ELISA) was evaluated. The serological test methods were compared by using sera obtained from 30 entamoebiasis histolytica patients and 130 normal health individuals. The highest sensitivity was obtained with the method of ELISA, followed by IFA and IHA : the lowest was obtained with MGDP. On the contrary, the high specificity was obtained with IHA, IFA, MGDP : the lowest was obtained with ELISA. Intensity of the antibody titers in IHA was correlated well with that of IFA. In addition, we studied antibodies nonspecifically reactive to Entamoeba histolytica in sera from E. histolytica-negative individuals with high CRP patients with regard to the sensitivity and specificity. Among 101 sera examined, six showed false positive results of which five were the sera with extremely high CRP.

Animals↗

[Neonatal hypoxic/ischemic encephalopathy: neuropathology and plasticity].

To obtain some clues for early management after neonatal hypoxic/ischemic brain injury, the cascade of cellular responses to the lesions was examined. Microglia is one of the principal glial element that responds to ischemic lesions. Microglia and astroglia may play important roles in neuronal degeneration and regeneration through secretion of some substances, such as neurotrophic factors which have been known to protect and/or rescue injured neurons. Platelet-derived growth factor B chain PDGF-B chain) is one of the neurotrophic factors, and an immediate enhancement of the expression of PDGF-B chain mRNA, protein and its receptor was observed in the injured brain. This enhancement persisted longer only in the neurons in the peri-infarct. Our findings suggested the crucial role of PDGF-B chain in the impending brain injury, as a neuroprotecting factor. Clinical application of neurotrophic factors is not anecdotal.

Animals↗

Early and delayed technetium-99m-tetrofosmin myocardial SPECT compared in normal volunteers.

UNLABELLED: This study was performed to test the feasibility of early SPECT imaging with 99mTc-tetrofosmin with the presence of high hepatic activity. METHODS: Thirteen normal volunteers were injected 600-740 MBq of 99mTc-tetrofosmin at rest and were imaged at 10 min and 1 hr after injection. The SPECT images were reconstructed for 180 degrees 360 degrees data. The early and delayed SPECT and anterior planar projection images were analyzed. RESULTS: After excluding one subject because of high hepatic activity overlapping to the myocardium, 4 of 12 subjects (33%) had abnormal scans with reduced uptake in the inferior wall on the early 180 degrees SPECT image. In contrast, only one (8%) showed equivocally reduced uptake on the 360 degrees SPECT image. In the delayed images, all subjects had a normal 180 degrees and 360 degrees SPECT scan. Quantitative data showed reduced regional activities in the inferior wall on the early SPECT scan, especially in the 180 degrees data. There were no changes in the mean anterior-to-inferior ratio in the anterior planar projection images over time, suggesting that the reduced activity in the early SPECT images reflected an artifactual effect. CONCLUSION: Our data indicate that it would be best to perform late imaging in patients with suspected coronary artery disease using 99mTc-tetrofosmin.

Adult↗