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T Kojima

Publications and source records attributed to T Kojima.

At least 415 records · Page 23Linked to original sources
PubMed1995

The subarachnoid space as a site for precursor T cell proliferation and effector T cell selection in experimental autoimmune encephalomyelitis.

To characterize the phenotype of inflammatory cells in the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE), Lewis rats were immunized with guinea pig myelin basic protein and frozen sections of the spinal cord with EAE were examined immunohistochemically using a panel of monoclonal antibodies against T cells and adhesion molecules. In addition, double immunostaining was performed with glial and T cells markers to examine the interaction between infiltrating T cells and reactive brain cells during the course of EAE. In the early stage of EAE, inflammatory cells first appeared in the subarachnoid space (SAS) and infiltrated the subpial region. The majority of inflammatory cells in SAS expressed TCR alpha beta and either CD4 or CD8 molecules. However, only CD4+ T cells infiltrated the parenchyma while the majority of CD8+ cells remained in SAS. A similar differential localization of T cells was observed with regard to CD45RC molecules. Inflammatory cells in SAS consisted of both CD45RC+ and CD45RC- population, while those in the parenchyma were largely CD45RC-. With regard to adhesion molecules, the leptomeninges constitutively expressed fibronectin (FN) and intercellular adhesion molecule 1 (ICAM-1). Most SAS inflammatory cells expressed very late activation antigen 4 (VLA-4) and, to lesser extent, lymphocyte function-associated antigen 1 (LFA-1) in the early stage of EAE. On the other hand, parenchymal infiltrating cells expressed LFA-1 more strongly in the peak stage. Double staining for V beta 8.2 TCR and microglia demonstrated an increase in the number of microglia together with morphological changes into rod-shape cells in the vicinity of infiltrating T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of auricular stimulation on feeding-related hypothalamic neuronal activity in normal and obese rats.

It is known that auriculotherapy occasionally affects dramatic body weight reduction for obese patients, although the physiological and anorexigenic functions are not clear. Effects of auricular stimulation on feeding-related lateral (LHA) and ventromedial (VMH) hypothalamic neuronal activity in normal and experimental (hypothalamic and dietary) obese rats were investigated. The LHA and/or VMH neuronal activity were recorded from feeding-related regions in Wistar SPF/VAF male and experimental (hypothalamic and dietary) obese rats, anesthetized with urethane-chloralose, under stereotaxic coordination. Recording was through 3 M KCI glass microelectrodes, while stimulating the ipsilateral vagal innervated region of the auricle. This is equivalent to the cavum conchae in the human, and was identified by resistance less than 10-50 k omega. The stimulating electrode was a stainless steel ear acupuncture (0.12 x 2.0 mm). The latency of potentials evoked in the LHA by unilateral stimulation of a specific site in the ear was 28.1 +/- 3.3 ms (8-92, n = 41). LHA neuronal activity was depressed 45.6% (n = 12, p < 0.01), and VMH activity was excited (60.5%, n = 18, p < 0.01). The auricular acupuncture stimulation clearly modulates feeding-related hypothalamic neuronal activity of experimental (both hypothalamic and dietary) obese rats. These auricle acupuncture stimulation effects were correlated to the degree of obesity. In conclusion, the results suggest that auricular acupuncture stimulation may not reduce appetite, but is more likely concerned with satiation formation and preservation. Thus, auricular acupuncture should be more effective on obese rats than on normal rats.

Acupuncture Therapy↗
PubMed1995

Investigation of applicability of alanine and radiochromic detectors to dosimetry of proton clinical beams.

Cancer therapy studies using proton accelerators are underway in several major medical centers in the U.S., Russia, Japan and elsewhere. To facilitate dosimetry intercomparisons between these laboratories, alanine-based detectors produced at the National Institute of Standards and Technology and commercially available radiochromic films were studied for their possible use as passive transfer dosimeters for clinical proton beams. Evaluation of characteristics of these instruments, including the LET dependence of their response of proton energy, was carried out at the Institute of Theoretical and Experimental Physics. Results of absolute dose measurements were regarded as a preliminary step of dose intercomparison between ITEP and NIST. Measurements made in a number of experiments showed average agreement between the ITEP and NIST dosimetry standards to 2.5%.

Alanine↗
PubMed1995

The high hepatocarcinogen susceptibility of LEC rats is genetically independent of abnormal copper accumulation in the liver.

We previously reported that LEC rats, which show a spontaneous occurrence of liver injury and hepatocellular carcinoma (HCC), are highly susceptible to chemical carcinogens such as diethylnitrosamine (DEN). Since abnormal copper accumulation in the liver of LEC rats was found to be a cause of liver injury, it is necessary to elucidate whether the carcinogen susceptibility of LEC rats is related to the accumulation of copper in the liver. In this study we have examined the relationship between the susceptibility of FI [LEC x LEA or LEC x Fischer 344 (F344)] and FI backcross rats to DEN and hepatic copper concentration, as copper accumulation has been demonstrated to be inherited as an autosomal recessive trait. The groups of F1 and F1 backcross rats were given a single intraperitoneal injection of DEN (20 mg/kg wt) and subjected to a modified Solt-Farber protocol for assaying glutathione S-transferase placental form (GST-P)-positive foci. The hepatic copper concentration was examined by atomic absorption. Although no F1 rats showed a high copper concentration in the liver, the numbers of foci were as high as those in LEC rats which accumulate copper. Backcross rats separated into high and low copper concentration groups at an almost 1:1 ratio, but there was no significant difference in the mean numbers of foci between these two groups. The results clearly indicate that the high susceptibility of LEC rats to DEN is genetically independent of copper accumulation in the liver. A possible dominant inheritance of this high carcinogen susceptibility was suggested. Biochemical measurement of cytochromes P450 and b5 in the liver of F1 rats indicated that alterations in drug metabolizing enzymes may be partially responsible for the high carcinogen susceptibility of LEC rats.

Animals↗
PubMed1995

Pustular psoriasis precipitated by acetazolamide.

We report a case of pustular psoriasis precipitated by acetazolamide, a carbonic anhydrase inhibitor. A 28-year-old man suffering from 20 years-standing generalized pustular psoriasis developed psoriatic arthritis and glaucoma and experienced a precipitation of pustular lesions and widespread erythema after initiation of oral acetazolamide for glaucoma. The cutaneous lesions and systemic symptoms improved after restriction of acetazolamide and administration of oral etretinate. Readministration of acetazolamide confirmed that generalized pustules arose within 24 hours.

Acetazolamide↗
PubMed1995

Dipyridamole combined with tumor necrosis factor-alpha enhances inhibition of proliferation in human tumor cell lines.

In the search for cytokines whose antiproliferative action could be enhanced by combination with dipyridamole, 2,6-bis(diethanolamino)-4,8-dipiperidinopyrimido[5,4-d]pyrim idine, the combination of tumor necrosis factor-alpha (TNF-alpha) with this agent was evaluated in various human tumor cell lines. Inhibition of the proliferation of human melanoma cell lines MM-1CB and HMV-1 by TNF-alpha (1-10(2) U/ml) was enhanced in culture dishes by combination treatment with dipyridamole (0.1-10 microM). The enhancement effect was also detected in other tumor cell lines: T98 (glioma), SCC-1CB (squamous cell carcinoma), HAC-2 (ovarian clear-cell carcinoma), HLE (hepatoma), HEC-1 (endometrial adenocarcinoma) and HOC-21 (ovarian serous cystadenocarcinoma). The incorporation of [14C]amino acids and [3H]uridine into acid-insoluble cell materials in the combination-treated cells was not significantly different from that in cells treated with TNF-alpha or dipyridamole. However, the incorporation of [3H]thymidine was specifically inhibited in all cell lines examined after more than 12 h of the TNF-alpha and dipyridamole combination treatment, although neither agent alone inhibited this incorporation. On the other hand, the growth of tumors induced by the injection of MM-1CB and HMV-1 cells into nude mice was more markedly inhibited by the subcutaneous administration of TNF-alpha in combination with orally administered dipyridamole than by either agent alone. The results presented suggested that dipyridamole is beneficial in assuring the effectiveness of anti-cancer cytokine therapy.

Amino Acids↗
PubMed1995

Unusual cutaneous manifestations of myelodysplastic syndrome.

We report a 58-year-old patient with acute myeloid leukaemia who developed an oedematous erythema resembling Sweet's syndrome, accompanied by atypical erythema nodosum and bullous pyoderma gangrenosum. Examination of skin biopsies showed dense infiltration with mature neutrophils, although there was peripheral blood leucocytopenia. The oedematous erythema worsened after he was treated with granulocyte-colony-stimulating factor (G-CSF), which was given for his leucocytopenia. We suggest that when a neutrophilic dermatosis complicates leukaemia, alternatives to G-CSF should be considered for the treatment of leucocytopenia. Corticosteroids were very effective in controlling the skin lesions in our patient.

Acute Disease↗
PubMed1995

Persistent chorea following cardiac surgery for congenital heart disease.

We describe a 6 year old girl with chorea following cardiac surgery, the first such report in Japan. The radical operation for total anomalous pulmonary venous return was carried out at the age of 11 months under hypothermia. Seven days after the operation, a sudden onset of irritability, dysphagia, chorea, generalized, hypotonia, and complete external ophthalmoplegia were seen. These symptoms diminished gradually, but chorea remained. We speculated that the cause of chorea arose from the cardiac surgery under hypothermia. It is necessary to consider 'cardiac surgery' as one of the triggers of certain movement disorders including chorea. We tried treatment with haloperidol, pimozide, and several other drugs; only pimozide was effective in decreasing chorea without any side-effects.

Cardiopulmonary Bypass↗
PubMed1995

Urinary trehalase activity is a useful marker of renal proximal tubular damage in newborn infants.

To clarify the reliability of urinary trehalase activity as a marker of cellular proliferation and/or damage of renal proximal tubules, the activity was examined in healthy newborn infants or infants treated with tobramycin, a drug known as causing tubular cell damage. Eighty-one newborn infants (56 mature infants and 25 premature infants) were enrolled in the study. Urinary trehalase was examined using a spot urine sample during the first 7 days of age and on the 10th day of age. A good positive correlation was observed between urinary trehalase activity/creatinine ratio (T/Cr) on the 10th day of age and conceptional age or body weight (n = 46, r = 0.58, p < 0.001). Urinary trehalase of 29 healthy mature infants was higher during the first few days of age, after which it decreased to an almost steady level. Urinary trehalase of 6 premature infants during the first few days of age was significantly lower than that of mature infants, after which it increased and became equal to that of the mature infants on the 7th day of age. Treatment with ampicillin (100 mg/kg) and tobramycin (5 mg/kg) of 6 mature infants with pneumonia for 6 days resulted in a significant elevation of the urinary T/Cr. The extent of this elevation was greater than that of the urinary N-acetyl-beta-D-glucosaminidase (NAG) activity/creatinine ratio (NAG/Cr). A significant correlation was observed between the urinary T/Cr and the urinary NAG/Cr (r = 0.67, p < 0.01) or gamma-glutamyl transpeptidase/creatinine ratio (r = 0.48, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Reappearance and long-term maintenance of connexin32 in proliferated adult rat hepatocytes: use of serum-free L-15 medium supplemented with EGF and DMSO.

Intercellular communication, especially gap junctional communication, is thought to be one of the highly differentiated functions of hepatocytes. In primary cultures of rat hepatocytes, it has been considered that the maintenance and the reinduction of differentiated functions is very difficult. In the present study, we succeeded in inducing the gap junctional protein connexin32 (Cx32) in adult rat hepatocytes cultured in serum-free L-15 medium supplemented with epidermal growth factor (EGF) and dimethylsulfoxide (DMSO). When the hepatocytes were cultured in L-15 medium supplemented with 20 mM NaHCO3 and 10 ng/ml EGF in a 5% CO2:95% air incubator, the cells proliferated. Fluorescence immunocytochemistry showed spots immunoreactive to Cx32 on the cell membranes between adjacent cells until day 3, but only a few Cx32-positive spots were found after day 4. Western and northern blot analyses also showed that the amounts of both the protein and mRNA of Cx32 in the cells decreased with time in culture. However, when the cells were treated with 2% DMSO from day 4, the immunoreactive spots reappeared on the cell membranes from day 6 and both their number and intensity gradually increased. The reappearance of Cx32 was accompanied by increases in both the protein and mRNA of Cx32. Furthermore, the expression of Cx32 was well maintained, together with extensive gap junctional intercellular communication, for more than 4 weeks. In addition, ultrastructurally, many gap junctional structures were observed between the hepatocytes, and the antibodies to Cx32 were shown to bind to those structures. This culture system may be useful for studies of the reconstruction of the gap junctional structure, the intracellular pathways of the proteins, and the regulation of synthesis and processing in differentiated hepatocytes.

Animals↗
PubMed1995

Induction and regulation of connexin26 by glucagon in primary cultures of adult rat hepatocytes.

In the adult rat hepatocyte, the gap junction proteins consist of a major component, connexin32 (Cx32) and a minor component, connexin26 (Cx26). Although we recently reported our success in inducing and maintaining Cx32 in adult rat hepatocytes cultured in serum-free L-15 medium supplemented with epidermal growth factor and 2% dimethyl sulfoxide, it was very difficult to induce Cx26 in the primary hepatocytes. In the present study, we found that the addition of 10(-7) M glucagon into the culture medium could dramatically induce Cx26 mRNA and protein. Although the expression of Cx32 mRNA was also influenced by glucagon, the increase of the expression was small. Immunocytochemically, Cx26-positive spots were observed between most adjacent cells and were co-localized with the Cx32-positive spots. We also examined whether 0.5 mM dibutyl cyclic AMP could induce expression of Cx26 in the cells. The effect of dexamethasone on the expression of Cx26 mRNA compared to that of Cx32 mRNA was examined. For the induction and maintenance of Cx26 mRNA, more than 10(-7) M dexamethasone was necessary in this culture. These results suggest that expression of Cx26 in hepatocytes may be regulated by the concentrations of glucagon and glucocorticoid hormones.

Animals↗
PubMed1995

TGF-beta completely blocks the formation of small-cell colonies: effects of mito-inhibitory factors on the proliferation of primary cultured rat hepatocytes.

The proliferation of primary cultured rat hepatocytes was observed in serum-free modified DMEM supplemented with 10 mM nicotinamide and 10 ng/ml EGF. These proliferating cells were mainly mononucleate and formed small-cell colonies after 4 days of culture. In the present experiment primary cultured hepatocytes were treated with Activin A, IL-1 beta, IL-6, and TGF-beta, which have been shown to be inhibitors of the DNA synthesis of rat hepatocytes, to examine whether these four inhibitors could suppress the formation of small-cell colonies. The initial DNA synthesis of more than 50% of the cells was dose-dependently inhibited by all the factors and the strongest inhibition was demonstrated in the cells treated with TGF-beta. Although Activin A and IL-6 did not block the colony development when the agents were administered at 96 h, just before the time when the cells started to form colonies, TGF-beta and IL-1 beta could inhibit the colony formation completely and partially, respectively. Transient treatment (48-72 h) with TGF-beta was enough to suppress colony development, while Activin A and IL-6 did not block the formation of colonies. IL-1 beta partially suppressed this formation. However, continuous administration (48-144 h) of IL-beta as well as TGF-beta stimulated the detachment of the cells from dishes and the remaining hepatocytes failed to form colonies. In addition, only TGF-beta could inhibit the DNA synthesis of most small cells in the established colonies as well as that of relatively large hepatocytes. Neither Activin A, IL-1 beta nor IL-6 could inhibit the DNA synthesis of the small cells. Thus, only TGF-beta could completely inhibit both the DNA synthesis of any type of hepatocyte and the formation of small-cell colonies.

Activins↗
PubMed1995

Effects of phosphoramidon on endothelin-1 and big endothelin-1 production in human aortic endothelial cells.

Using cultured human aortic endothelial cells, we examined the effects of phosphoramidon, an endothelin converting enzyme (ECE) inhibitor, on the release of endogenous endothelin-1 (ET-1) and big endothelin-1 (big ET-1), and on the generation of ET-1 from exogenously applied big ET-1. Phosphoramidon, at concentrations of 10(-6) to 2 x 10(-4) M, caused a biphasic alteration of the ET-1 release, i.e., at lower concentrations of the drug, there were slight but unexpected increases of the release, whereas higher concentrations led to a decrease which is due to the drug-induced inhibition of ECE. The former effect appears to be based on the inhibition of ET-1 degradation by neutral endopeptidase 24.11 (NEP), since kelatorphan, a specific NEP inhibitor, produced a similar increasing effect on ET-1 release. Phosphoramidon enhanced the big ET-1 release from the cells in a concentration-dependent manner. When high concentrations of phosphoramidon were added, there was a dramatic increase in the release of big ET-1, which cannot be explained only by the drug-induced inhibition of ECE. This increase in big ET-1 release appeared to be partly due to a transient stimulation of the expression of prepro ET-1 mRNA. The amount of ET-1 generated from exogenously applied big ET-1 was markedly decreased by phosphoramidon in a concentration-dependent manner. In a similar fashion, phosphoramidon markedly inhibited ECE activity of the membrane fraction of cultured cells. Thus, ET-1 generation from exogenously applied big ET-1 reflects the functional phosphoramidon-sensitive ECE activities in human aortic endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1995

Radiofrequency catheter ablation for the treatment of common atrial flutter in humans.

Endocardial catheter ablation has been recently been proposed for the treatment of arrhythmias originating in the right atrium. In this study, we used this technique in 5 patients with paroxysmal common atrial flutter and 3 patients with paroxysmal uncommon atrial flutter. Various antiarrhythmic agents had failed to prevent the recurrence of these episodes. In each procedure, we used a large-tip 7 F quadripolar catheter electrode that was introduced via the femoral vein into the lower part of the right atrium. The two distal electrodes were used to record double-spike potentials or fragmented electrograms. A unipolar electrogram recording from a distal electrode of the same catheter was also used to identify local activation. The targets for ablation were sites which showed double-spike potential and fragmented electrogram 40-60 msec earlier than the onset of the F wave. Application of radiofrequency (RF) energy (25-40 watts) (3-17 applications) terminated atrial flutter and prevented reinduction of atrial flutter in the 5 patients with common atrial flutter. However, atrial flutter could not be terminated with the application of RF energy in the 3 patients with uncommon atrial flutter. The sites at which ablation was successful were located inferior or posterior to the coronary sinus ostium between the inferior vena cava and the tricuspid valve annulus, and were characterized by double-spike potentials and fragmented electrograms with activation times > or = 40 msec before the onset of the F wave. This area may represent the exit site from the area of slow conduction, since pacing from this site showed concealed entrainment of the F wave, and a local electrogram to the onset of the F wave coincided with the pacing spike to the onset of the F wave. Follow-up of these 5 patients (19.4 +/- 10.4 weeks) revealed recurrence of the original atrial flutter in 1 patient and a new type of atrial flutter in 1 patient. The other 3 patients have been episode-free, although an antiarrythmic agent was given for the treatment of paroxysmal atrial fibrillation in 2 patients. We conclude that the application of RF energy to the presumed critical area in the atrial flutter reentrant circuit seems to be effective in terminating and preventing common atrial flutter. Long-term follow-up is required for the recurrence of atrial flutter.

Adolescent↗
PubMed1995

Effects of atrioventricular intervals on right atrial monophasic action potential duration during pacing or reciprocating tachycardia.

We evaluated the relationship between changes in the atrioventricular (AV) intervals and right atrial monophasic action potential duration at 90% repolarization (RA-MAPD90) in humans. In 4 patients, RA-MAPD90 was measured during AV reciprocating tachycardia (AVRT, n = 2) or AV node reentrant tachycardia (AVNRT, n = 2) and atrial or ventricular pacing at similar cycle lengths. In 10 patients, RA-MAPD90 was measured during continuous atrioventricular sequential pacing at AV intervals of 0, 50, 100, 150, 200, 250, 300, 350 msec for 90 sec at a cycle length of 333-400 msec. In patients with AVRT, the RA-MAPD90 during tachycardia was shorter than RA-MAPD90 during RA or RV pacing. In patients with AVNRT, RA-MAPD90 during tachycardia was similar or longer than RA-MAPD90 during RA or RV pacing. As the AV interval was increased from 0 msec to 150 msec, the peak right atrial pressure decreased from 8-12 mmHg to 2-3 mmHg. RA-MAPD90 decreased to its minimal value at an AV interval of 150 msec. The maximal difference in the RA-MAPD90 obtained by changing the AV interval was 22.5 +/- 3.0 msec. We conclude that 1) a very short AV or VA interval causes an increase in RA-MAPD90 which correlates with an increase in RA pressure, and 2) RA-MAPD90 during supraventricular tachycardia is different from RA-MAPD90 during atrial or ventricular pacing. Thus, a contraction-excitation feedback mechanism may exist in the human atrium.

Action Potentials↗