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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 577 records · Page 32Linked to original sources

[Transcriptional control by steroid receptor].

Nuclear receptors for steroid/thyroid hormones, vitamin A,D and fat-soluble ligands form a gene superfamily of ligand-inducible transcription factors, which plays an important roles in a wide spectrum of biological events by regulating expression of a set of target genes. Two domains (A/B and E) of nuclear receptors are demonstrated to activate transcription, designated AF-1 (A/B) and AF-2 (E), respectively. Homo- and hetero-dimers of nuclear receptors bind target enhancer elements in the target gene promoters. The target enhancer elements are referred as hormone response elements (HRE), and composed of two hexamer core motifs. The orientations and spaces between two core motifs play critical roles in discreminating the recognition of HREs among the members of nuclear receptor. DNA-bound nuclear receptors controls transcription in a ligand-binding dependent way in co-operation with a multiprotein complex containing RNA polymerase II and a series of auxiliary factors, TFIIA,B,D, E,F and H. During process of ligand-induced transactivation by nuclear receptors, nuclear co-factors interacting with the AF-1 and AF-2 seem to be involved. Several transcriptional co-activators and co-repressors have been recently identified, and their function is currently under investigation.

Gene Expression↗

[Evaluation of peritoneal lavage smears and intraperitoneal administration of anti-neoplastic agents in stage III and IV gastric cancer].

Examinations of peritoneal lavage smears (cy) in gastric cancer surgical stages III and IV are very important for determining the disease stage. We have been carrying out these examinations for 8 years. One hundred sixty patients with gastric cancer were examined. The incidence of cy positivity was higher in T4 than in T3, and higher in P1,2,3 than in P0. We performed intraperitoneal administration of CDDP in 10 patients with gastric cancer using a reservoir (Infuse-A-Port) implanted in the abdominal wall once a week. No difference in survival was observed between patients who received chemotherapy via i.p. and those who received it i.v.

Adenocarcinoma↗

[Enlargement of the femoral marrow cavity with aging].

Bone resorption and bone formation occur throughout life. We measured CT film from the femora of human subjects and studied how remodeling change affected the size of marrow cavities in long bones. In total of 448 subjects using the right femora ranging in age from 16 to 95 years, 293 males and 155 females were studied. The part measured was the upper one-forth of the femora. A positive correlation in regards to age, circumference, and area of marrow cavities was demonstrated in male and female subjects (p < 0.001). Marrow cavities were found to grow with age. The percentage of growth in marrow cavities was greater in female subjects than in male subjects. However, the rate of marrow cavity enlargement with age differed in male subjects compared with female subjects. We grouped our data into three categories: group 1 (under 40 years), group 2 (40-60 years), and group 3 (over 60 years). We found a large difference between group 2 and group 3 of male subjects. This difference suggests that a reduction in bone volume with age affects bone marrow enlargement. A large difference in females between group 1 and group 2 was noticed, but a difference in females between group 2 and group 3 was not observed. In female subjects, change in marrow cavity enlargement occurred in subjects in their 40's and 50's. We speculate that the reason for enlargement of the bone marrow in subjects in their 50's is due to a reduction of bone volume after postmenopausal change.

Adolescent↗

Tissue specific-distribution and metabolism of vitamin A are affected by dietary protein levels in rats.

The effect of dietary protein levels on tissue-specific distribution and metabolism of vitamin A was studied in rats given [15-14C] retinol (14C-ROH). The weanling rats were fed a low level vitamin A diet for 10 days, then rats (15 rats per group) were divided into 2 groups; one was given a 40% casein diet as a high protein diet (HP-diet), and the other a 5% casein diet as a low protein diet (LP-diet). After 10 days feeding on these diets, 14C-ROH (5 microCi/rat) was given to both groups, HP-diet and LP-diet, by intraperitoneal injection. The radioactivity in the exhalated gases, urine and feces was measured to estimate the rate of vitamin A metabolism. The tissue specific-distribution of ROH was studied in terms of the radioactivities of the ROH fractions separated by HPLC. The hepatic 14C-ROH content in the HP-diet group was lower than that in the LP-diet group at 24, 48, and 72 hours after administration of 14C-ROH. In contrast, 14C-ROH content in serum, spleen, pancreas, and small intestinal mucosa in the HP-diet group was higher than that in the LP-diet group. The radioactivity of the exhalated gas and feces was higher in the HP-diet group. These results suggest that metabolism of vitamin A is higher with intake of a HP-diet. Thus, dietary protein levels may affect tissue-specific distribution and metabolism of vitamin A, thereby modulating the actions of this vitamin.

Animals↗

[Allogeneic bone marrow transplantation in children from related donors other than HLA-identical siblings].

Thirty-five children with poor-prognosis disease underwent allogeneic bone marrow transplantation (BMT) from related donors other than HLA identical siblings (parents in 18 cases, non-identical siblings in 14, and other relatives in 3). Phenotypically identical donors were involved in 12 cases, donors with one mismatched locus in 17, and donors with two or more mismatched loci in 6. Thirty-two of the children received total-body irradiation as part of their conditioning regimen, followed by unpurged marrow-cell infusions (averaging 4.09 x 10(8) cells/kg). Methotrexate and cyclosporin were administered for graft-versus-host disease (GVHD) prophylaxis; 15 of the children also received antithymocyte globulin (ATG) infusions. The effective graft rate for the group was 84. 8%; of 5 patients who experienced rejections, 4 had non-malignant diseases. The incidence of grade II-IV acute GVHD was 48.4%, significantly higher than that for groups that received allogeneic BMT from matched sibling donors. Three children (8.8%) died of severe GVHD. The incidence of acute GVHD in phenotypically matched patients was the same as that in the one-locus mismatched cases. MLC reactivity affected the incidence of acute GVHD (60.0% MLC-positive, 28.6% negative). ATG reduced the severity of acute GVHD. The event-free survival rate was 40.8 +/- 8.5% for the entire group (N = 35; 32.9 +/- 10.5% for the 22 children with malignancies, and 53.8 +/- 13.8% for the 13 with non-malignant diseases). Despite the risk of severe GVHD, allogeneic BMT from related donors other than HLA-identical siblings seems to be an effective treatment for patients with poor-prognosis diseases.

Acute Disease↗

[Evaluation of the FREEDOM O2, DC Concentrator, a portable oxygen concentrator capable of operating under car battery power].

UNLABELLED: The FREEDOM O2 DC Concentrator, an oxygen concentrator which can be powered by a car battery, was evaluated. The oxygen concentrator was used by a 67 year-old man with sequelae of pulmonary tuberculosis who was receiving long-term oxygen therapy at home (HOT), and whose work required automobile trips over long distances. The equipment used was an adsorption-type oxygen concentrator capable of operating on a DC 12 V power supply, and which can be powered from a residential power outlet (AC 100 V) using a dedicated voltage converter. The trunk-shaped equipment measured 21/584 x 42 cm and weighed 17 kg. The noise level of the equipment was 58.2 +/- 2.5 dB (at 1 meter), and the flow rate can be set to 0.25, 0.50, 0.75, 1.0, 1.5, and 2.0 l/min. RESULTS: 1) The O2 concentration which can be generated by this equipment is 93 +/- 3% (0.25 to 1.5 l/min) or 90 +/- 2.8% (2.0 l/min). 2) Using this equipment, the patient was capable of driving himself in comfort for two hours or longer. Further, it was possible to stay in a hotel during a trip, inhaling oxygen generated by the equipment. Hereafter, this equipment should enable or facilitate long-distance driving, travel and lodging for HOT patients.

Aged↗

Induction of Fas-mediated apoptosis in a human renal epithelial cell line by interferon-gamma: involvement of Fas-mediated apoptosis in acute renal rejection.

To examine the role of the Fas ligand/Fas (FasL/Fas) system and apoptosis in renal allograft rejection, we analyzed FasL/Fas expression and apoptosis in 63 renal allograft biopsy specimens obtained from 56 renal transplant recipients in Tokyo, Japan. Sixteen biopsy specimens were diagnosed (Banff criteria) as acute rejection (AR), 17 as AR plus chronic rejection, 10 as borderline stages, and 20 as no rejection (NR). Immunohistochemically, Fas antigen was highly expressed in the renal tubular epithelium in tissues from patients with rejection. The mean number of Fas-positive tubular epithelium was significantly higher in biopsy specimens with AR than in those with NR, but FasL expression was highly expressed in infiltrating lymphocytes in the interstitium of allografts with cellular rejection. The mean number of FasL-positive infiltrating lymphocytes was significantly higher in specimens with AR than in those with NR or borderline stages. For detection of apoptotic cells, the specimens were subjected to terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling, which showed that the mean number of tubular epithelial cells positive for this labeling was highest for the specimens with AR, the number being significantly higher than in those with AR plus chronic rejection or with NR. Thus, Fas expression on epithelial cells might actively trigger their apoptosis by the interaction between Fas and FasL. Studies of human normal renal-derived cell lines (RPTEC 2601 [epithelial] and NHMC 5155 [mesangial]) showed that both constitutively expressed Fas (but not FasL) mRNA. After pretreatment with interferon-gamma, Fas-induced apoptosis was observed in the RPTEC 2601 line, but without interferon-gamma pretreatment, anti-Fas-mediated apoptosis was not seen. Under identical conditions, the NHMC 5155 line was resistant to anti-Fas-mediated apoptosis regardless of interferon-gamma pretreatment. This suggested that AR might be associated with increased apoptosis in the renal tubular epithelial cells mediated by the Fas/FasL system.

Acute Disease↗

Ca2+ channel inhibition by endomorphins via the cloned mu-opioid receptor expressed in NG108-15 cells.

Endomorphin-1 and -2, recently isolated endogenous peptides specific for the mu-opioid receptor, inhibited Ca2+ channel currents with EC50 of 6 and 9 nM, respectively, in NG108-15 cells transformed to express the cloned rat mu-opioid receptor. On the other hand, they elicited no response in nontransfected NG108-15 cells. It is concluded that endomorphin-1 and -2 induce Ca2+ channel inhibition by selectively activating the mu-opioid receptor.

Analgesics, Opioid↗

Prominent sensory and autonomic disturbances in familial amyotrophic lateral sclerosis with a Gly93Ser mutation in the SOD1 gene.

A missense mutation (Gly93-->Ser) was identified in exon 4 of the Cu/Zn superoxide dismutase (SOD1) gene of a 48-year-old Japanese man with familial amyotrophic lateral sclerosis (FALS). The SOD1 activities in the fibroblasts and in a lysate of erythrocytes of the patient did not differ from those of healthy controls. The clinical characteristics of the patient were fairly slow progression of the illness, prominent sensory impairment, urinary disturbance and blood pressure fluctuation due to sympathetic hyperactivity. The severe sensory and autonomic disturbances, association of which with FALS has not been previously reported, may represent specific clinical features associated with the Gly93Ser mutation or may indicate the variability of clinical findings even in patients with the same mutation.

Amyotrophic Lateral Sclerosis↗

PACAP stimulates pancreatic exocrine secretion via the vagal cholinergic nerves in sheep.

The present study evaluates the possible role of the vagus nerves in mediating the stimulatory effect of PACAP-27, PACAP-38 and VIP on the exocrine pancreas, especially on enzyme secretion which is atropine sensitive in sheep. The animals were equipped with two cannulae into the common bile duct, a duodenal cannula, and a ruminal cannula under anesthesia. The bilateral cervical vagus nerves were coiled with a cooling device. In conscious animals, the peptides were infused intravenously for 10 min at 10 pmol kg(-1)min(-1) in phase II of the duodenal migrating motor complexes and the same peptide infusion was repeated in the reversible cooling blockade of the vagus nerves. Increment in fluid secretion was not significantly altered by the vagal blockade in all the peptide infusions, while increment in bicarbonate ion by only PACAP-27 was inhibited by the vagal blockade. Increments in protein and amylase output decreased significantly to 32.0+/-5.0 and 23.2+/-2.6% in PACAP27, and to 26.1+/-7.7 and 20.8+/-6.4% in PACAP-38 in the vagal blockade, but the increments by VIP did not decrease. These results demonstrate that circulating PACAP stimulates pancreatic enzyme secretion via the vagal cholinergic preganglionic neurons in sheep, suggesting the central action of PACAP.

Amylases↗

Bovine oocytes from early antral follicles grow to meiotic competence in vitro: effect of FSH and hypoxanthine.

A large number of oocytes are contained in the mammalian ovary. A very small number of these oocytes grow to the final size, mature, and are ovulated. In the ovary there are more early antral follicles than late antral or preovulatory follicles, offering a large pool of oocytes for IVM and IVF if appropriate culture conditions could be devised. In the present study, early antral follicles containing oocytes 90 to 99 microm in diameter were isolated from bovine ovaries. Cumulus-oocyte complexes (COC) with pieces of parietal granulosa (COCG) were then dissected from the follicles. The COCGs were embedded in collagen gels and cultured in Medium 199 with 10% fetal calf serum (FCS) for 8 d. In Experiment 1, the effect of hypoxanthine and FSH on the growth of bovine oocytes was examined. When hypoxanthine (2 and 4 mM) and FSH (10 ng/ml) were added to the culture medium, the number of granulosa cell-enclosed oocytes increased significantly (P < 0.05). All of the oocytes surrounded by granulosa cells showed a normal morphology and were at the germinal vesicle stage, while 75 to 94% of the denuded oocytes were degenerated and had resumed meiosis. The mean diameter of the oocytes showing normal morphology was significantly higher than that measured before culture (P < 0.05). In Experiment 2, the maturational competence of in vitro-grown bovine oocytes was examined. Oocytes which were 90 to 99 microm in diameter before culture did not have meiotic competence. After being in a growth culture of 4 mM hypoxanthine- and 10 ng/ml FSH-supplemented medium for 7 or 11 d, granulosa cell-enclosed oocytes were recovered from the COCGs. No significant difference (P < 0.05) in the diameters of the oocytes was observed between 7 and 11 d of culture (7 d: 107.5 +/- 6.1 microm, n = 30; 11 d: 108.0 +/- 5.3 microm, n = 35). After a subsequent 24 h in a maturation free of hypoxanthine and FSH medium, only 17% of the oocytes cultured for 7 d underwent germinal vesicle breakdown. On the other hand, 89% of the oocytes cultured for 11 d underwent germinal vesicle breakdown, and 11% of the oocytes emitted the first polar body and reached metaphase II. These results demonstrate for the first time that bovine oocytes harvested from early antral follicles can grow, and acquire meiotic competence in vitro.

Journal Article↗

Tau immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy.

In order to clarify the manner and significance of tau expression in glial cytoplasmic inclusions (GCIs), ubiquitinated oligodendroglial abnormal structures in multiple system atrophy (MSA), an immunohistochemical study was carried out in the lesions of the pontine nuclei of 10 cases of MSA using antibodies against various epitope locations of tau protein. As a result, tau-2 was constantly but weakly positive in ubiquitinated GCIs in each case (from 28.6 to 66.7%). However, tau-2-immunoreactivity in GCIs was not correlated to the density of ubiquitin-positive GCIs or preserved pontine neurons. Antibodies against tau proteins of N-terminal or C-terminal failed to label GCIs, although a few number of GCIs were occasionally positive for tau-1 after dephosphorylation. In comparison with the knowledge on tau-immunoreactivity of coiled bodies (CBs) in oligodendroglia in progressive supranuclear palsy (PSP) or corticobasal degeneration, GCIs are quite different from CBs which have a wide range of epitope location of tau proteins, including N-terminal and C-terminal. This study suggests that expression of tau proteins in GCIs is not related to the essential neurodegenerative process in MSA but induced by non-specific stress in oligodendroglia, unlike CB in various 'tau diseases' such as PSP.

Aged↗

25-Hydroxyvitamin D3 1alpha-hydroxylase and vitamin D synthesis.

Renal 25-hydroxyvitamin D3 1alpha-hydroxylase [1alpha(OH)ase] catalyzes metabolic activation of 25-hydroxyvitamin D3 into 1alpha, 25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], an active form of vitamin D, and is inhibited by 1alpha,25(OH)2D3. 1alpha(OH)ase, which was cloned from the kidney of mice lacking the vitamin D receptor (VDR-/- mice), is a member of the P450 family of enzymes (P450VD1alpha). Expression of 1alpha(OH)ase was suppressed by 1alpha, 25(OH)2D3 in VDR+/+ and VDR+/- mice but not in VDR-/- mice. These results indicate that the negative feedback regulation of active vitamin D synthesis is mediated by 1alpha(OH)ase through liganded VDR.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Outcome of radiation therapy for patients with Kasabach-Merritt syndrome.

PURPOSE: The efficacy of radiation therapy for Kasabach-Merritt syndrome, which is characterized by a huge hemangioma with consumption coagulopathy, remains controversial. In this study, we retrospectively investigated the treatment outcome of radiation therapy for seven neonates with Kasabach-Merritt syndrome. METHODS AND MATERIALS: During the past 25 years we have seen seven children with Kasabach-Merritt syndrome who were treated with radiation therapy. Their ages ranged from 1 day to 5 months, with a median age of 1 month. The hemangioma was located in the extremities in four of seven children. Tumor sizes ranged from 70 cm to more than 150 cm in greatest diameter. Initial platelet counts were all less than 40,000/mm3 except for one patient. In principle, the total dose applied to the hemangioma was 8-10 Gy, with a daily dose of 1 Gy five times a week. RESULTS: Four of seven hemangiomas responded dramatically, with a concomitant rise of the platelet count to radiation therapy. Although the remaining three hemangiomas, all of which were ill circumscribed by widespread overlying shiny, dusky purple skin, became less tense during radiation therapy. Disseminated intravascular coagulopathy was not improved, but they have responded favorably to two or three courses of radiation therapy with an extended radiation field by 1.5 years of age. As a result, all seven patients are now surviving with no evidence of hemangioma or hematological abnormalities. Shortening of the extremity was observed in three patients who received multiple courses of radiation therapy. CONCLUSIONS: Radiation therapy appears to be one of the effective treatment options for Kasabach-Merritt syndrome despite the risk of growth delay and malignancy.

Disseminated Intravascular Coagulation↗

Thymic microvascular system.

Morphological studies of the microcirculatory system in the thymus were reviewed in regards to methodology and structural organization of blood and lymphatic vessels. The blood capillaries and postcapillary venules (PCVs) in the thymus are characterized by a double-walled structure. These vessels are surrounded more or less by perivascular spaces (PVSs) containing many lymphocytes. This space is delimited on the one side by abluminal surface of the vascular endothelium and on the other side by cytoplasmic processes of epithelial reticular cells. There are interruptions or gaps on the outer epithelial reticular layer. The lymphatic vessels can be distinguished histochemically from blood vessels based on strong 5'-nucleotidase (5'-Nase) activity. The 5'-Nase-positive lymphatic vessels were seen predominantly in the capsule and interlobular connective tissue but sometimes in the immediate vicinity of the PVS around the PCV, when a discrete opening in the lymphatic wall next to the PVS was found. Thus, it may be regarded as an initial part of lymphatics closely associated with the PVS, suggesting a possible route for lymphocyte efflux into the lymphatic vessel from the PVS. The endothelial cells of lymphatic vessels as well as PCVs are often infiltrated by lymphocytes, particularly more heavily during acute involution of the thymus. These images represent the migration of lymphocytes into the blood or lymphatic microcirculation.

Animals↗