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Biomedical subjects

H Kasai

Publications and source records attributed to H Kasai.

At least 217 records · Page 12Linked to original sources
PubMed1994

Increased formation of oxidative DNA damage, 8-hydroxydeoxyguanosine, in human livers with chronic hepatitis.

8-Hydroxydeoxyguanosine (oh8dG) is a promutagenic DNA lesion produced by oxygen radicals. We examined alterations in the oh8dG level in human livers which have chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The oh8dG content in livers with chronic hepatitis was significantly higher than the oh8dG content in normal livers (P < 0.05). There was also a significant correlation between the oh8dG content in noncancerous liver tissues with individual serum alanine aminotransferase concentration (r = 0.515; P < 0.001). Thus, chronic inflammation in the liver produces oxidative DNA damage, which may increase the risk for genomic alterations causing hepatocarcinogenesis.

Alanine Transaminase↗
PubMed1994

Two distinct glutamatergic synaptic inputs to striatal medium spiny neurones of neonatal rats and paired-pulse depression.

Excitatory postsynaptic currents (EPSCs) were recorded from the medium spiny neurones of neonatal rat striatal slices using the whole-cell patch clamp method. EPSCs were selectively elicited in the presence of picrotoxin with a glass stimulating pipette placed in the striatum. We found two distinct unitary EPSCs that were evoked by stimulation of single presynaptic fibres. The major type of EPSC, termed 'S-type', failed frequently and had a small mean amplitude (2.05 pA). They probably represented cortical afferents. The other type of unitary EPSC, the 'H-type', seldom failed and was 13 times larger than the S-type. Spontaneous EPSCs with amplitudes similar to those of H-type EPSCs could be induced. H-type EPSCs were mediated by both non-NMDA and NMDA receptors. The two types of EPSCs could be evoked in the same neurons. The intensity of stimulation for H-type EPSCs was higher than that for S-type EPSCs. H-type EPSCs could be polysynaptically activated, suggesting the presence of glutamatergic interneurones in the striatum that generated H-type EPSCs. H-type EPSCs displayed particularly long-lasting paired-pulse depression, while that displayed by the S-type EPSCs was short. The paired-pulse depression of both EPSCs was Ca2+ dependent and involved presynaptic mechanisms. We have demonstrated that the medium spiny neurones of neonatal rats receive two different glutamatergic input systems having different amplitudes, origins and paired-pulse depression, reminiscent of cerebellar Purkinje cells. This suggests that the two types of EPSCs also play distinctive roles in striatal neuronal circuitry.

Animals↗
PubMed1994

Quantal properties of S-type glutamatergic synaptic input to the striatal medium spiny neuron from neonate rat.

We investigated the quantal properties of the small glutamatergic EPSPs (S-type EPSPs) in the striatal medium spiny neurons using the whole-cell recording method. Amplitudes of unitary glutamatergic EPSCs displayed a single peak at about 4.7 pA that was unaffected by decreasing external Ca2+. This indicates that afferent fibers contact the medium spiny neuron with only a few, possibly one, release sites which generate no more than one quantum of EPSCs at a time.

Animals↗
PubMed1994

Another family with tricho-rhino-phalangeal syndrome type III (Sugio-Kajii syndrome).

Tricho-rhino-phalangeal syndrome Type III (TRPS III) is a newly defined genetic entity. Only 9 patients in a family and one sporadic patient have been reported. We add another family in which 4 individuals in 3 generations are affected with this autosomal dominant trait. Although they manifested short stature, sparse hair, "pear-shaped" nose, and cone-shaped epiphyses, sharing these findings with TRPS Type I, the presence of a severe form of generalized shortness of all phalanges and metacarpals, and the absences of mental deficiency and exostoses in this family distinguish the disorder from the TRPS Types I and II. Their manifestations are quite similar to those of the patients reported as TRPS III (Sugio-Kajii syndrome).

Abnormalities, Multiple↗
PubMed1994

Comparative study of inhibitory effects by murine interferon gamma and a new bisphosphonate (alendronate) in hypercalcemic, nude mice bearing human tumor (LJC-1-JCK).

The inhibitory effect of murine interferon gamma (muIFN gamma) on humoral hypercalcemia in nude mice bearing lower-jaw cancer (LJC-1-JCK), in which parathyroid-hormone(PTH)-related protein is responsible for causing humoral hypercalcemia by activating bone resorption, was examined in comparison with that of a new bisphosphonate, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (alendronate). muIFN gamma was injected into tumor-bearing nude mice for 5 days before the establishment of hypercalcemia. The increase of plasma calcium concentration was delayed and this effect continued for more than 6 days even after the injection was stopped. Alendronate markedly suppressed hypercalcemia in tumor-bearing nude mice but this inhibitory effect continued for less than 6 days. Neither muIFN gamma nor alendronate affected the tumor volume or serum PTH-related protein concentration. Injection of muIFN gamma into mice for 3 days almost completely abolished the formation of multinucleated osteoclast-like cells from bone marrow cells in vitro, whereas injection of alendronate into mice had no effect. These findings suggested that muIFN gamma suppressed the formation of osteoclasts, resulting in the prolonged decrease of plasma calcium concentration in hypercalcemic tumor-bearing nude mice, whereas alendronate is cytotoxic to functionally mature osteoclasts and inhibited osteoclastic bone resorption, resulting in a marked decrease in the plasma calcium concentration in tumor-bearing hypercalcemic nude mice.

Adult↗
PubMed1994

Accumulation of autofluorescent yellow lipofuscin in rat tissues estimated by sodium dodecylsulfate extraction.

Autofluorescent yellow lipofuscin accumulated in the older Wistar rat brain, kidney, spleen and testis was successfully extracted by use of 0.5% sodium dodecylsulfate (SDS)/0.05 M phosphate buffered saline (pH 7.4). The extracts contained three fluorophores, one of which corresponded to yellow lipofuscin and showed an excitation maximum at 400 nm and an emission maximum at 620 nm. The SDS extraction method was found suitable for the accurate quantification of lipofuscin in rat tissues. Lipofuscin thus determined accumulated in brain, kidney, spleen and testis with the increase of age of rats. It was found that kidney was the most susceptible tissue in lipofuscin accumulation, and accumulation in male rat kidney was much higher than that in female rat kidney. Accumulation of lipofuscin in rat tissues was slightly dependent on the lipid peroxidation state of the tissues and the dietary conditions: a vitamin E-adequate, vitamin E-deficient, vitamin E-excessive and oil-rich diet, except that the accumulation in male and female rat kidney was significantly enhanced when fed a vitamin E-deficient diet for 7-10 weeks.

Aging↗
PubMed1994

Spatial dynamics of second messengers: IP3 and cAMP as long-range and associative messengers.

Recent imaging experiments have revealed the distinct spatial dynamics of second-messenger actions. In general, actions of Ca2+ tend to be local, whereas those of other messengers such as inositol 1,4,5-trisphosphate (IP3) and cAMP are long range. In pancreatic acinar cells, IP3 generated at the base can diffuse across the cell and evoke a spatially confined Ca2+ signal in the apical pole, triggering enzyme and fluid secretion. Similar mechanisms might also operate in other cell types. We propose that the distinct dynamics of messengers might be relevant to neuronal function: IP3 and cAMP could convey signals over long distances along neurites, and serve as mediators for association and co-operation, for example, during learning.

Animals↗
PubMed1994

Characteristics of the hepatocarcinogenesis caused by dehydroepiandrosterone, a peroxisome proliferator, in male F-344 rats.

The characteristics of the hepatocarcinogenesis induced by dehydroepiandrosterone (DHEA) were compared with that induced by other peroxisome proliferators such as [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) and di(2-ethylhexyl)phthalate (DEHP). Male F-344 rats were given a diet containing DHEA at 0.5 or 1%, Wy-14,643 at 0.1% and DEHP at 2% for up to 78 weeks. In rats fed 0.5 or 1% DHEA the incidence of neoplasias was 20% after 52 weeks. At 78 weeks all rats treated with 1% DHEA had numerous grossly visible nodules and the incidence of hepatic neoplasia was dose-dependent. The magnitude of hepatocellular tumorigenicity after DHEA treatment was less potent than that after Wy-14,643, but more than that after DEHP treatment. Peroxisomal beta-oxidation activity increased three- or six-fold after a 10 week course of 0.5 or 1% DHEA respectively and this was significantly lower than that induced in Wy-14,643- or DEHP-fed rats. From 52 to 78 weeks these activities increased 3-9 times over that in controls. In both the group of rats treated with Wy-14,643 and those treated with DEHP, peroxisomal beta-oxidation constantly increased 11- to 15-fold during the experiment. Catalase activity increased 1.3- to 1.5-fold for the first 10 weeks of DHEA treatment and then recovered to the control level. The activities of glutathione peroxidase and glutathione S-transferase decreased markedly after 30 weeks in DHEA-treated rats and the decreases were sustained for up to 78 weeks. The profile of changes in enzyme activities in the rats fed DHEA was not significantly different from that of those fed Wy-14,643 or DEHP. There were no increases in 8-hydroxydeoxyguanosine, oxidative DNA damage or lipid peroxide level in the liver in any of the treated rats at 10 or 30 weeks. Since these results showed that the characteristics of hepatocarcinogenesis caused by DHEA were basically similar to those caused by Wy-14,643 and DEHP, typical peroxisome proliferators, hepatocarcinogenesis induced by DHEA is probably due to the same mechanisms as that induced by general peroxisome proliferators.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

Pharmacological properties of endothelin receptor subtypes mediating positive inotropic effects in rabbit heart.

The positive inotropic effect (PIE) of endothelin (ET) isoforms, ET-1 and ET-3, was similar in that 1) the PIE was associated with prolongation of isometric contractions, 2) the maximal response was approximately 60% of that to isoproterenol (Isomax), 3) the PIE was associated with acceleration of PI hydrolysis, and 4) it was selectively antagonized by phorbol 12,13-dibutyrate. Because the concentration-response curve for ET-1 was biphasic (whereas that for ET-3 was monophasic), ET-1 had a PIE greater than ET-3 up to 10(-8) M. ET-1 induced a PIE at 3 x 10(-14) M and higher, which reached a plateau of 10-20% of Isomax at 10(-12) M (first phase); the curve became steeper at 10(-9) M and higher (second phase), achieving the maximal response at 10(-7) M to 3 x 10(-7) M. An ETA-selective antagonist, BQ-123, did not affect the PIE of ET-1 up to 10(-7) M; it abolished the first phase at 10(-6) M but did not affect the second phase. BQ-123 at 10(-8) to 10(-6) M antagonized the PIE of ET-3, [Thr2]sarafotoxin S6b, and [Glu9]sarafotoxin S6b in a concentration-dependent manner. The PIE of ET-3 was abolished by 10(-6) M BQ-123. An ETB-selective partial agonist IRL-1620 neither elicited a PIE nor affected the PIE of ET-3. These findings indicate that the PIE of ET receptor agonists on rabbit ventricular myocardium cannot be totally explained by occupancy of the ETA or ETB receptor.

Animals↗
PubMed1994

Human T lymphotropic virus type I associated myelopathy and myasthenia gravis: a possible association?

We report the first known patient with human T lymphotropic virus type I (HTLV-I) associated myelopathy (HAM) and myasthenia gravis (MG). A 50-year-old woman developed fluctuating muscle weakness with easy fatigability, transient bilateral blepharoptosis and double vision. Spastic paraparesis complicated these symptoms. Neurological assessments and specific laboratory findings revealed that the patient had definite HAM and MG. By inference from decreasing serum anti-HTLV-I antibody titers after thymectomy, the presence of antigenicity for HTLV-I in the thymic reticular cells, and a high incidence of various coexistent autoimmune diseases in HAM or MG, we suggested the possibility that these two diseases were associated with each other and with HTLV-I infection.

Adult↗
PubMed1994

Examination of the extraction methods and re-evaluation of blue fluorescence generated in rat tissues in situ.

Extraction methods for measuring blue fluorescence generated in rat liver and brain in situ were examined. Great care should be taken when the traditional chloroform/methanol extraction method is employed because artificial blue fluorescence is readily produced by subsequent light irradiation, or by passage through a silicic acid column. In contrast, sodium dodecylsulfate (SDS) extraction were found to be suitable since no artificial blue fluorescence was produced by subsequent light irradiation. The levels of blue fluorescence in rat tissues were re-evaluated following SDS extraction. The levels of blue fluorescence in rat liver increased with age, whereas those in rat brain did not. Accumulation of blue fluorescence in the tissues was only slightly enhanced by vitamin E-deficiency. Blue fluorescence in the extracts did not seem to be derived from autofluorescent yellow lipofuscin in situ. The results were not always consistent with earlier observations obtained using the chloroform/methanol extraction.

Aging↗
PubMed1994

[Effective measures against side effects by increasing ACNU dose for malignant glioma: effects on digestive organs].

Loading therapy consisting of the ACNU regimen was instituted as postoperative anticancer chemotherapy for malignant gliomas. The efficacy rate of the regimen was 25% at a dose of 3 mg/kg. A high incidence of hematological changes, such as leukopenia (neutropenia) and thrombocytopenia, were observed after chemotherapy. The former could be prevented by the administration of G-CSF, but platelet infusions were necessary in some patients for amelioration of thrombocytopenia. Gastroenterological symptoms, such as nausea and vomiting, were also frequently noted. Granisetron (Kytril), which is a recently developed selective competitive inhibitor of the 5-HT3 receptor, was used for the treatment of these adverse effects, and was found to be clinically effective.

Adult↗
PubMed1994

[A new assessment of quality of life (QOL) for cancer patients].

A new assessment of quality of life (QOL) was made for cancer patients. The QOL assessment consists of 12 items: pain; nausea; constipation; general fatigue; sleep; eating; activity; a daily life pattern; conversation; treatment acceptability; satisfaction at the present status and family exhaustion. Ranges of scores are one (best) to five (worst). For visual expression of QOL, the author made an original method called "QOL diagram", drawn with a circle which has 12 diverging lines marked five points indicating the score for each item. QOL changes after cancer pain control with either oral or intravenous morphine were examined in 22 adult cancer patients by the QOL assessment. Laxatives and anti-nausea drugs were mostly prescribed at the same time in order to avoid side effects of morphine. QOL was evaluated and recorded by the author through an individual interview with each patient. It was observed that the psychological factors were improved along with pain relief. Although items such as general fatigue, nausea, constipation, sleep and eating did not change considerably at first, they improved well with time in the oral morphine group. On the other hand, there was no marked time-dependent change in the intravenous morphine group. Items such as activity, a daily life pattern and conversation were rather negative than positive. These items seem to be more important to improve QOL of the cancer patients, in particular, whose general status is relatively good. In conclusion, the QOL diagram helped us to follow subtle changes of status and needs of cancer patients. And it enables us to easily assess risks and benefits of the treatment plans including palliative care and home supportive programs. It is designed for both patients and medical staffs to use easily and repeatedly. However, the further evaluation and refinement will be needed to verify validity and reliability of the QOL diagram before a routine clinical application.

Activities of Daily Living↗
PubMed1993

Critical intracellular Ca2+ concentration for all-or-none Ca2+ spiking in single smooth muscle cells.

Neurotransmitters induce contractions of smooth muscle cells initially by mobilizing Ca2+ from intracellular Ca2+ stores through inositol 1,4,5-trisphosphate (InsP3) receptors. Here we studied roles of the molecules involved in Ca2+ mobilization in single smooth muscle cells. A slow rise in cytoplasmic Ca2+ ([Ca2+]i) in agonist-stimulated smooth muscle cells was followed by a wave of rapid regenerative Ca2+ release as the local [Ca2+]i reached a critical concentration of approximately 160 nM. Neither feedback regulation of phospholipase C nor caffeine-sensitive Ca(2+)-induced Ca2+ release was found to be required in the regenerative Ca2+ release. These results indicate that Ca(2+)-dependent feedback control of InsP3-induced Ca2+ release plays a dominant role in the generation of the regenerative Ca2+ release. The resulting Ca2+ release in a whole cell was an all-or-none event, i.e. constant peak [Ca2+]i was attained with agonist concentrations above the threshold value. This finding suggests a possible digital mode involved in the neural control of smooth muscle contraction.

Animals↗
PubMed1993

Identification of 8-hydroxyguanine glycosylase activity in mammalian tissues using 8-hydroxyguanine specific monoclonal antibody.

Here we report the finding of glycosylase activity in mammalian tissues to remove 8-hydroxyguanine residues from DNA. To detect this activity, a synthetic duplex DNA containing an 8-hydroxyguanine residue was used as the substrate, and before the product was analyzed by HPLC-electrochemical detection (ECD), 8-hydroxyguanine released by the enzymatic action was specifically collected from reactions using immunoaffinity columns of 8-hydroxyguanine specific monoclonal antibody. With the application of immunoaffinity column chromatography, a single peak of 8-hydroxyguanine free from many interfering peaks of unknown origin was clearly demonstrated in HPLC-ECD even with crude tissue extracts used as assay materials. All the tissues of the rats examined showed the activity, suggesting its presence is ubiquitous. The present coupled technique of immunoaffinity column chromatography and HPLC-ECD will be very useful to many future studies of 8-hydroxyguanine glycosylase such as its activity detection, characterization and purification, etc.

Animals↗