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Biomedical subjects

M Kubo

Publications and source records attributed to M Kubo.

At least 307 records · Page 17Linked to original sources

[Chronic inflammatory demyelinating polyneuropathy associated with chronic liver disease due to type B and type C hepatitis virus].

A patient with chronic inflammatory demyelinating polyneuropathy (CIDP) associated with type B and type C hepatitis virus infection is reported. A 54-year-old female who had a blood transfusion at the age of 31 years was diagnosed as a carrier of hepatitis B virus at the age of 43. Liver dysfunction was first noted in 1987 and gradually grew worse year by year. Beginning in early June 1992, the patients general fatigue became worse, her serum GOT and GPT levels became elevated, and she complained of a tingling sensation in her arms and legs. Neurological examination revealed moderate sensory disturbance of the glove-and-stocking type in all of her extremities. Deep tendon reflexes were all diminished. Hepatitis C antibody was detected in the serum at this time. On June 12, 1993, progression of her sensory disturbance was found to be associated with generalized muscle weakness. Cerebrospinal fluid studies showed increased protein without pleocytosis. Motor nerve conduction studies revealed marked prolongation of terminal latencies, reduction of conduction velocities, and abnormal temporal dispersion of the motor potentials. No sensory potentials could be evoked at any of the sites stimulated. Sural nerve biopsy showed segmental demyelination and severe loss of large myelinated fibers as well as some onion bulb formation. A diagnosis of CIDP was made. Treatment with corticosteroids was started, but there was little improvement in neurological function. The liver dysfunction progressed further and ultimately the patient died of hepatic failure. An autopsy demonstrated liver cirrhosis, but no malignant tumors were evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Disease↗

[A case of variant Gerstmann-Sträussler-Scheinker disease with the mutation of codon P105L].

Here we present a case of variant GSS disease with mutations in codons 1055 and 129 in a prion protein. The patient was a 54-year-old male, who developed weakness in the lower limbs and spastic, wide-based gait at the age of 46 years. Subsequently he developed dementia and spastic quadriplegia at the age of 49. He had marked pseudobulbar palsy at the age of 50 and became bed-ridden in decorticated posture at teh age of 53. CT and MRI examinations revealed marked atrophy of the frontal and temporal lobes, but the occipital lobes and the cerebellum were spared. His sister had been reported by Amano, et al. in 1992 as a case of variant GSS syndrome, who had very similar clinical features, and had numerous prion protein positive plaques in her cerebral cortex at the time of autopsy. His sister was confirmed to have the same mutations in a prion protein as the present case in later genetic studies.

Atrophy↗

Activation of the interleukin-4 gene is controlled by the unique calcineurin-dependent transcriptional factor NF(P).

Cyclosporin A-sensitive promoter activity that is induced by the T cell antigen receptor was identified in the region between base pairs -147 and -17 of the mouse interleukin (IL)-4 gene. Here, we identify a transcriptional factor, NF(P), that binds a sequence from -75 to -69 (ATTTTCC) of the mouse IL-4 gene which corresponds to the human IL-4 gene P sequence. Expression of NF(P) was associated with positive regulation of the IL-4 gene and cyclosporin A sensitivity. The P sequence is homologous to the binding site for the positive transcriptional regulator of the IL-2 gene nuclear factor of activated T cells (NFAT). Binding of NF(P) to the P sequence was completely inhibited by an oligonucleotide corresponding to the NFAT binding site. Like NFAT, NF(P) was also found in the cytosol of resting T cells but translocated to the nucleus via a cyclosporin A-sensitive mechanism after T cell activation. Overexpression of a constitutively active calcineurin caused translocation of NF(P) from the cytosol to the nucleus. NF(P) purified on an oligonucleotide affinity column was 90 kDa, which is smaller than the 120-kDa reported for cNFAT. Purified NF(P) did not bind the NFAT consensus sequence, even in the presence of AP-1 protein. Our results suggest that the NF(P) molecule is not identical to the cNFAT molecule.

Animals↗

Signal-averaged electrocardiographic late potentials in children with complete heart block.

The purpose of this study was to examine signal-averaged electrocardiographic (SA-ECG) late potentials to predict ventricular arrhythmias during intrinsic cardiac rhythm and during ventricular pacing in children with complete heart block (CHB). Recordings of SA-ECG were obtained from eight patients (aged 3-18 years) with documented CHB. The etiology of CHB was congenital in four cases and acquired in four cases. Six of these patients underwent permanent pacemaker implantation. Comparisons of the SA-ECG were made before and during ventricular pacing. Abnormalities of SA-ECG during intrinsic cardiac rhythm were noted in four patients, all of whom were older than 14 years. Although there was no significant difference in SA-ECG parameters between patients with congenital CHB and acquired CHB, abnormal SA-ECG was noted in one of four patients with congenital CHB and in three of four patients with acquired CHB. Two patients without permanent pacemaker implantation had normal SA-ECG, but four of six patients with permanent pacemaker implantation had abnormal SA-ECG. Three of the four patients had abnormal SA-ECG during ventricular pacing, but the abnormal SA-ECG in one patient had normalized during ventricular pacing. It is important to record SA-ECG before and during ventricular pacing to detect late potentials in patients with CHB. It may be useful to record SA-ECG while changing the pacing site to find ideal sites for electrode implantation for the potential prevention of ventricular arrhythmias.

Action Potentials↗

Immunoelectron microscopic localization of fibronectin in cultured human keratinocytes.

We investigated the ultrastructural localization of fibronectin (FN) in cultured human keratinocytes using an improved method of peroxidase-immunoelectron microscopy. This method enabled us to visualize the precise localization of FN within the cells while preserving the morphology. FN was localized in the protein synthetic and secretory organelles, including the rough-surfaced endoplasmic reticulum, Golgi complex, multivesicular bodies and perinuclear space. It was also detected in the extracellular space, on small regions of the villous projections of cell membranes at the site of secretion and at cell-substratum contact sites. These findings confirm that human keratinocytes synthesize, secrete and deposit FN in the pericellular matrix.

Cells, Cultured↗

Time course of oxygen uptake and heart rate during Bruce treadmill test in patients following surgery for tetralogy of Fallot.

Exercise performance was examined in 14 patients with a prior history of surgical repair for tetralogy of Fallot. Using a Bruce protocol, we evaluated the time course of oxygen uptake and heart rate in these patients and compared them with a standard curve obtained from 63 sex- and age-matched healthy children. Five of the 14 patients had unusual findings. The heart rate increased rapidly in four of them, while the oxygen uptake increased gradually (95% confidence lower limit). It is hypothesized that a reduction in stroke volume during exercise was responsible for these abnormal findings. The remaining unusual finding was in a patient who was known to have myocardial fibrosis and vacuolization. In this particular case, the time course of oxygen uptake and heart rate were both below the 95% coefficient of variation from the beginning to the end of exercise. In patients who have undergone surgical repair for tetralogy of Fallot, the analysis of oxygen uptake time course and the heart rate may provide valuable information for the long-term follow-up.

Adolescent↗

Osteochondritis dissecans of the patellofemoral groove in athletes: unusual cases of patellofemoral pain.

Five athletes who developed osteochondritis dissecans in the patellofemoral groove in the course of sports events at high school and college league level are described. They were male athletes complaining of anterior knee pain. When examining young people engaged in violent sports, it is well to remember that they might have osteochondritis dissecans in the patellofemoral groove. Clinically, four of the five patients under discussion were characterized by tight movements of the patella in a direction parallel to its transversal axis. X-ray studies in lateral projections and CT scans provided useful tools for definitive diagnosis, but AP radiography was no help in diagnosis. Release of a tight lateral retinaculum with or without drilling on the degenerated cartilage was effective in the treatment of osteochondritis dissecans of the patellofemoral groove in three of the four patients.

Adolescent↗

The Ca2+/calmodulin-activated, phosphoprotein phosphatase calcineurin is sufficient for positive transcriptional regulation of the mouse IL-4 gene.

We have studied the TCR mediated signal transduction pathways involved in transcriptional regulation of the mouse IL-4 gene. The sequences extending from base pair -766 to +63 of the IL-4 gene were inserted upstream of a luciferase indicator gene. Transcriptional activity was observed when the construct, [pIL-4(-766)], was transfected into either the IL-4 producing cell line, EL-4, or the IL-4 non-producing T cell hybridoma, 68-41, but not in the L929 fibroblast cell line. By analysis of deletion mutants of pIL-4(-766), we identified a transcriptional regulatory element that is tightly associated with a signal coming from the TCR and which controls inducible activation of the IL-4 promoter. By analysis of deletion mutants of pIL-4(-766), this latter element was found between base pairs -147 to -17. Electrophoretic mobility shift assays indicated that expression of a nuclear binding protein with binding sites between base pairs -84 and -55 could be induced. By competition and mutation analysis, the binding motif of this protein was determined to be AAAATTTTCC. Stimulation with ionomycin alone was sufficient to induce activity in pIL-4(-766). Cyclosporin A inhibited both the IL-4 promoter activity and activation of the inducible nuclear protein. Transient over-expression of a constitutively active form of the Ca2+/calmodulin-regulated protein phosphatase, calcineurin was sufficient to cause activation of pIL-4(-766) without any additional stimulus. These results indicate that the signaling requirements for activation of upstream positive regulatory elements of the IL-4 gene are distinct from those of the IL-2 gene. Ca2+ mobilization is sufficient to activate the IL-4 promoter, whereas IL-2 gene transcription requires both Ca2+ mobilization and protein kinase C activation.

Animals↗

Oral administration of BOF-A2 to rats with lung transplanted tumors results in increased 5-fluorouracil levels.

A new tumor model was developed in which solid Yoshida sarcoma tissue injected intravenously developed into tumors in the lungs of about 30% (13/42) of the inoculated rats. Histological examination revealed that alveoli were occupied with tumor cells and the tumors were similar to those obtained by subcutaneous inoculation. Using this model, the concentrations of 5-fluorouracil (5-FU) in tumor tissue 12 h after oral administration of 3-[3-(6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl)-benzoyl]-1-ethoxy methyl- 5-fluorouracil (BOF-A2, 36 mumol/kg) or a combination of tegafur and uracil in a molar ratio 1 to 4 (UFT, 50 mumol/kg) were found to be 129.8 ng/g and 19.2 ng/g, respectively. Thus, compared to treatment with UFT, BOF-A2 resulted in higher levels of 5-FU in lung tumor tissues. Increased concentrations of 5-FU should have a superior anti-tumor effect and so BOF-A2 merits clinical trial in the treatment of patients with lung cancer.

Administration, Oral↗

Importance of recall and follow-up screening for chronic hepatitis C in children receiving blood products prior to 1990 in Japan.

The objective was to detect chronic hepatitis C virus infection in recipients of blood products using retrospective analysis by recall and enrollment of recipients. 226 patients who received blood products for open heart surgery from January 1983 to June 1992 were examined for HCV antibody by using a second generation assay and liver function test. 22 (14%) of the 161 patients who received blood products before November 1989 had detectable HCV antibody, but none of the 65 recipients receiving blood products after 1990, the year the Japanese blood bank began to screen for HCV-antibody. Abnormal alanine aminotransferase (ALT) levels, more than 25 iu/L, during the chronic phase of HCV infection was recognized in nine of 22 (41%) seropositive patients. The liver function test and second generation HCV antibody in the serum are effective markers to screen for chronic hepatitis C in blood product recipients transfused before 1990.

Adolescent↗

Isolation and characterization of soybean waste-degrading microorganisms and analysis of fertilizer effects of the degraded products.

Two microorganisms which could degrade soybean lees efficiently were isolated and identified as Bacillus circulans and B. stearothermophilus. These two strains secreted thermostable proteases into the medium and could digest soybean lees rapidly and completely at 50 degrees C. Initially, the soybean lees were degraded to proteins in approximately 20 h by these two strains, after which time the concentrations of peptides in the medium gradually increased. The degraded products from soybean lees contained abundant nitrogen compounds, such as peptides, amino acids, and amides. Approximately 10 times more fresh plant weight was obtained (in the case of Brassica campestris) when these degraded products were applied than when water was applied for 42 days. These stimulatory effects of the soybean lees products were almost equal to those of a chemically synthesized fertilizer.

Bacillus↗

Presence of a capsule in Erysipelothrix rhusiopathiae and its relationship to virulence for mice.

Three avirulent insertional mutants of Erysipelothrix rhusiopathiae were obtained by the technique of transposon mutagenesis with the self-conjugative transposon Tn916. The interactions between murine polymorphonuclear leukocytes and parent and mutant strains were studied in vitro. In the presence of normal serum, the virulent parent strain was resistant to phagocytosis, whereas the avirulent mutant strains were efficiently phagocytosed. In the presence of immune serum, the parent and the mutant strains were both efficiently phagocytosed. Electron microscopic examination of the parent strain demonstrated the presence of a structure resembling a capsule which was absent on the mutant strains, suggesting that a capsule may be involved in virulence. This was confirmed in studies in which an avirulent mutant strain reverted to virulence following acquisition of a capsule when the transposon was lost by spontaneous excision. These results strongly suggest that virulence of E. rhusiopathiae is associated, at least in part, with resistance to phagocytosis by polymorphonuclear leukocytes and that this antiphagocytic ability of the bacterium results from its possession of a capsule.

Animals↗

Atrial natriuretic factor and isosorbide dinitrate modulate the gating of ATP-sensitive K+ channels in cultured vascular smooth muscle cells.

The effects of atrial natriuretic factor (ANF) and isosorbide dinitrate (ISDN), activators of particulate and soluble guanylate cyclase, respectively, on K+ currents were investigated in patch-clamp recordings of smooth muscle cells cultured from rat thoracic aorta. In the cell-attached patch configuration, ANF enhanced Ca(2+)-activated K+ (KCa) channel activities as reported previously. When KCa channels were blocked with 1 mmol/L tetraethylammonium or 10(-7) mol/L charybdotoxin, ANF and ISDN applied to the bathing solution activated ATP-sensitive K+ (KATP) channels without altering channel conductance. Pretreatment with methylene blue, a guanylate cyclase inhibitor, abolished the effects of ISDN on KATP channels, whereas 8-bromo-cGMP activated these channels, suggesting that the effects of ISDN on KATP channels were mediated by cGMP. Our results suggest that vasorelaxant agents that increase intracellular cGMP concentrations modulate the gating of two major potassium channels, ATP sensitive and Ca2+ activated, that might play an important role in controlling vascular tone by changing the membrane potential.

Adenosine Triphosphate↗

Studies on rehmanniae radix. I. Effect of 50% ethanolic extract from steamed and dried rehmanniae radix on hemorheology in arthritic and thrombosic rats.

Effects of 50% ethanolic extract (JR-ext) from Chinese Rehmanniae Radix (the steamed and dried root of Rehmannia glutinosa, "Jyuku-Jio" in Japanese) on the hemorheology of inflammatory, thrombosic and intact animals were examined in the in vivo models. JR-ext (200 mg/kg, p.o.) inhibited the reduction of fibrinolytic activity and erythrocyte deformability, the decrease in erythrocyte counts and the increase in connective tissue of the thoracic artery in a chronic inflammatory model, adjuvant-induced arthritis. However, JR-ext was ineffective on the development of edema in the arthritic rats and on acute and chronic inflammation. JR-ext inhibited the reduction of erythrocyte deformability, but not the decrease of coagulative factors in a thrombosic model, endotoxin-induced disseminated intravascular coagulation (DIC). JR-ext also showed a promoting effect on erythrocyte deformability and fibrinolytic activity in intact rats. These results suggest that orally administered JR-ext can prevent an inducement of impediment in the peripheral microcirculation of various chronic diseases through the improvement of hemorheology.

Acetates↗

Studies of cuticle drugs from natural sources. II. Inhibitory effects of Prunus plants on melanin biosynthesis.

The inhibitory effects of 50% ethanolic extracts from dried leaves of 38 plants collected in the herbal garden of Kinki University were investigated in vitro on melanin biosynthesis which is closely related to hyperpigmentation. Of the 38 extracts, Prunus yedoensis, P. zippeliana, P. amygdalus, P. persica, P. armeniaca, Thea sinensis and Chaenomeles sinensis showed a potent inhibition of tyrosinase, the enzyme which converts 3-(3,4-dihydroxyphenyl)alanine (dopa) to dopachrome in the biosynthetic process. Furthermore, the extracts from the leaves of P. yedoensis and P. zippeliana among the Prunus plants used in this experiment inhibited the production of melanin from dopachrome by autoxidation. These inhibitory effects of P. zippeliana on melanin biosynthesis were observed in cultured B-16 mouse melanoma cells. These results suggest that the leaves of P. zippeliana inhibit melanin biosynthesis which is involved in hyperpigmentation and could be used as a whitening agent for the skin.

Animals↗

Study of various rhubarbs regarding the cathartic effect and endotoxin-induced disseminated intravascular coagulation.

Sennoside A content in hot-water extracts from 17 varieties of rhubarb obtained from the market was measured, and their respective cathartic effects were also examined in mice. A positive correlation was confirmed between the sennoside A content and cathartic effects in our experiments. Furthermore, the effects of Shisendaio [symbol: see text], with a higher sennoside A content, and Kinmondaio [symbol: see text], with a lower sennoside A content, exhibited endotoxin-induced disseminated intravascular coagulation (DIC) which related closely to Oketsu symptoms, and these effects were examined in rats. Kinmondaio exhibited weak inhibition on both reducing erythrocyte deformability and prolonging euglobulin lysis time (ELT) in DIC rats. From our results, it is possible to evaluate rhubarb's cathartic effect, one of its main drug effects, by examining the rhubarb's sennoside A content. However, it is difficult to estimate the cathartic effect according to the general market name of Rhubarb. No dramatic effect was found on the experimental models used for Oketsu symptoms such as endotoxin-induced DIC.

Administration, Oral↗

Properties of three proteinases functioning at G1, S and G2 phases in HeLa cells and their inhibition by guanidino- and amidino-acid esters.

HeLa cells were synchronized by double thymidine-block and allowed to grow after removal of thymidine. Three proteinases, tryptase 17:17, proteinase In and late G2 proteinase, were prepared from the HeLa cells harvested at the time when each proteinase appeared in the cell cycle of the cells. All of them were suggested to be trypsin-like serine proteinases, because they hydrolyzed trypsin-specific fluorogenic substrates and their activities were inhibited by benzamidine, soybean trypsin inhibitor, leupeptin, tosyl-L-lysine chloromethan (TLCK) and diisopropylfluorophosphate (DEP). However, the actions of these proteinases on the substrates and inhibitors suggested that they were three different proteinases. They were strongly inhibited by 4-tert-butylphenyl and biphenyl esters of trans-4-guanidinomethylcyclohexanecarboxylic acid, amidinopiperidine-4-acetic and 4-propionic acids, which retard the second DNA synthetic (S) and mitotic (M) phases for 3h, 4-tert-butylphenyl ester of amidinopiperidin-4-carboxylic acid, which blocks initiation of S phase, the ester of amidinopiperidine-4-butyric acid, which suppresses the second S and M phases, and the esters of trans-4-amidinocyclohexanecarboxylic and 4-propionic acids which inhibit M phase.

Amino Acid Sequence↗