Search PubMed⌕ Search

Biomedical subjects

M Kubo

Publications and source records attributed to M Kubo.

At least 145 records · Page 8Linked to original sources

Gene expression of gastric type mucin (MUC5AC) in pancreatic tumors: its relationship with the biological behavior of the tumor.

Previously it has been found that the MUC2 gene for intestinal type secretory mucin is highly expressed in intraductal papillary mucinous tumors (IPMT), which are characterized by non-invasive growth and a favorable outcome. In contrast, MUC2 mRNA is rarely expressed in invasive ductal carcinomas (IDC), which have poor outcomes. The gastric type secretory mucin, MUC5AC, is strongly expressed in the surface mucous cells of gastric mucosa. As both MUC2 and MUC5AC mucins share the characteristics of forming highly viscous gels, it is expected that not only MUC2 mucin expression but also MUC5AC mucin expression may be associated with a favorable prognosis in patients with pancreatic tumors. MUC5AC mucin gene expression was examined in 24 cases of IPMT and 38 cases of IDC by in situ hybridization using a digoxigenin-labeled oligonucleotide. The results were compared with MUC2 mucin gene expression. Neither MUC5AC mRNA nor MUC2 mRNA was detected in normal pancreatic tissues. MUC5AC mRNA was expressed in 20 of 24 cases of IPMT (83%) and in five of 38 cases of IDC (13%). In contrast, MUC2 mRNA was expressed in 14 of 24 cases of IPMT (58%) and in none of the 38 cases of IDC (0%). The expression rates of MUC5AC mRNA and MUC2 mRNA in IPMT were significantly higher than those in IDC (P< 0.001, respectively). Intraductal papillary mucinous tumors are characterized by three histological types: (i) villous dark cell type; (ii) papillary clear cell type; and (iii) compact cell type. The villous dark cell type generally expressed both MUC5AC+ and MUC2+ genes. Alternatively, the papillary clear cell type and the compact cell type usually showed MUC5AC+ and MUC2- expression. Patients with MUC5AC mRNA expression had a significantly better survival prognosis than those with no MUC5AC mRNA expression (P< 0.005). In conclusion, MUC5AC gene expression occurs in a majority of IPMT cases, even in those with no MUC2 production. MUC5AC expression can be

Adenocarcinoma, Mucinous↗

Why couldn't an accurate diagnosis be made? An analysis of 1044 consecutive autopsy cases.

The protocols of 1044 consecutive patients autopsied between 1983 and 1997 at Sumitomo Hospital (Osaka, Japan) were retrospectively analyzed and the findings were compared with clinical diagnoses. In 73 cases, the clinical diagnosis apparently differed from the autopsy findings, and in six cases the origin of a malignant neoplasm remained unsolved even at autopsy. Of the 73 discrepant cases, 24 were a result of clinician misjudgment and a neglect to conduct further examinations. Missed diagnosis due to an erroneous pathological report, technical error of endoscopy, and misleading results obtained by new non-invasive technologies accounted for seven, nine, and 11 cases, respectively. Twenty-two cases were missed because the clinician could not carry out precise examination. It is concluded that advances in diagnostic technology and medical knowledge have not reduced the value of an autopsy.

Autopsy↗

Prevalence and antigen specificity of anti-histone antibodies in patients with polymyositis/dermatomyositis.

Anti-histone antibodies have been detected in the sera of patients with various autoimmune diseases. The existence of anti-histone antibodies in patients with polymyositis/dermatomyositis, however, has not been reported. We found anti-histone antibodies in eight (17%) of 46 sera from patients with polymyositis/dermatomyositis by an enzyme-linked immunosorbent assay. One serum was positive for both IgG anti-histone antibodies and IgM anti-histone antibodies. Six sera were positive only for IgG anti-histone antibodies. One serum was positive only for IgM anti-histone antibodies. An indirect immunofluorescence analysis using HEp-2 cells as the substrate showed that all sera positive for anti-histone antibodies produced homogeneous nuclear fluorescence. This immunofluorescence pattern disappeared after absorption of anti-histone activity with total histones. An immunoblotting analysis demonstrated that the anti-histone antibodies were predominantly directed against histone H1 in all seven sera with IgG anti-histone antibodies. Weak reactivity with H2B and H4 were also found in three sera from the patients with polymyositis/dermatomyositis. Sera from two patients with polymyositis/dermatomyositis displayed anti-H2A and H3 activity. One of the two sera showed IgM anti-histone antibodies in the enzyme-linked immunosorbent assay reacted with H1, H2A, H2B, H3, and H4, whereas the other serum reacted with no fractions of total histones. The activity of anti-histone antibodies disappeared in immunoblotting after absorption with total histones. All of the patients with anti-histone antibodies were free from lung fibrosis or internal malignancies. Thus, our data indicate that the presence of anti-histone antibodies is classified as one of the serologic abnormalities observed in polymyositis/dermatomyositis.

Adolescent↗

Effect of hyperinsulinemia on renal function in a general Japanese population: the Hisayama study.

BACKGROUND: Insulin resistance and hyperinsulinemia induce glomerular hypertension and hyperfiltration, which may result in glomerulosclerosis. However, the relationship between hyperinsulinemia and renal function is uncertain. METHODS: To elucidate whether hyperinsulinemia plays a significant part in the initiation and development of renal dysfunction, we examined in 1988 the relationship between serum insulin and renal function on data from a cross-sectional community survey conducted among residents from Hisayama Town, Japan, who were aged 40 to 79 years old. A total of 1065 men (72.0% of the total population in the same age range) and 1381 women (79.0%) without renal failure (creatinine clearance of more than 30 ml/min) underwent a comprehensive examination, including a 75 g oral glucose tolerance test. RESULTS: The correlation analysis showed that serum insulin, blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglycerides, and body mass index were all negatively correlated with the reciprocal of serum creatinine level (P < 0.01), and alcohol intake was positively correlated (P < 0.05) in both sexes. High-density lipoprotein cholesterol and smoking habits were positively correlated (P < 0.05) in men. When the subjects were divided into quartiles based on the sum of fasting and two-hour postloading insulin levels, the averages of the reciprocal of serum creatinine were significantly lower in the fourth quartile (0.90 +/- 0.10 for men and 1.10 +/- 0.14 for women) compared with the lowest quartile (0.95 +/- 0.12 and 1.13 +/- 0.13, respectively) in both sexes (P < 0.05). In multiple regression analysis, the correlation between the sum of insulin levels and the reciprocal of serum creatinine remained significant even after controlling for age, sex, body mass index, blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, alcohol intake, and smoking habits. We could not find appropriate correlations of creatinine clearance calculated by the Cockcroft-Gault formula with the covariates including serum insulin. CONCLUSIONS: The findings of this study suggest that hyperinsulinemia is a significant relevant factor of renal function in the general population.

Adult↗

Spondylolysis at three sites in the same lumbar vertebra.

We report a rare case of spondylolysis that occurred at 3 sites in the fifth lumbar vertebra involving the bilateral pars interarticularis and the center of the right lamina. This is the first such case in the world literature.

Adolescent↗

Isolation and characterization of a novel HS1 SH3 domain binding protein, HS1BP3.

We have isolated a novel gene, HS1BP3, which encodes an HS1 binding protein. Analysis of HS1BP3 cDNA indicates several potentially important segments, including a PX domain, a leucine zipper, immunoreceptor tyrosine-based inhibitory motif-like motifs and proline-rich regions. HS1BP3 associates with HS1 proteins in vivo as confirmed by immunoprecipitation in B and T cell lines. HS1BP3 preferentially associates with the HS1 SH3 domains rather than with other SH3 molecules, suggesting a role of HS1BP3 as an HS1 signaling mediator. Overexpression of mutant HS1BP3 protein in T cell lines results in decreased IL-2 production. Our data suggest a novel role for HS1BP3 in lymphocyte activation.

Adaptor Proteins, Signal Transducing↗

Role of class I major histocompatibility complex-restricted and -unrestricted suppression of human immunodeficiency virus type 1 replication by CD8+ T lymphocytes.

CD8+ T lymphocytes of asymptomatic human immunodeficiency virus type 1 (HIV-1) carriers (ACs) are capable of suppressing HIV-1 replication in CD4+ peripheral blood mononuclear cells (PBMC) by a variety of known and unknown mechanisms. In the present study, cell contact-dependent, major histocompatibility complex type I (MHC I)-unrestricted, CD8+ cell-mediated suppression of HIV-1 LAI replication was detected. CD8+ PBMC of ACs suppressed HIV-1 replication more efficiently in MHC I-matched CD4+ PBMC than in mismatched cells. However, even when MHC I was totally mismatched, CD8+ cells still suppressed replication to a considerable extent in CD4+ PBMC. This MHC I-unrestricted, CD8+ cell-mediated HIV-1 suppression required cell contact and was not effective against cells of the established T cell line ILT-KK. In contrast, MHC I-restricted HIV-1 suppression by CD8+ T cells was detected when ILT-KK cells were used as a target. By using these systems, we examined MHC I-restricted and -unrestricted suppressive activities of CD8+ cells in various donors in more detail. Although both types of CD8+ cell-mediated HIV-1 suppression diminished at the advanced stage of the infection, MHC I-unrestricted suppression diminished earlier than MHC I-restricted suppression, in parallel with the decline in CD4+ T cells. These results suggest that suppression by the MHC I-restricted mechanism alone may fail to protect against CD4+ T-cell loss at the late stage of infection.

CD4-Positive T-Lymphocytes↗

Molecular analysis of the genome of Chuzan virus, a member of the Palyam serogroup viruses, and its phylogenetic relationships to other orbiviruses.

The nucleotide sequence of the entire genome of Chuzan virus, which belongs to the Palyam serogroup orbiviruses and causes congenital abnormalities of cattle, has been completed by analysis of the genes encoding minor core proteins (VP1, VP4 and VP6) and non-structural proteins (NS1, NS2 and NS3). The genome of Chuzan virus is 18,915 bp in length and the coding capacity of its open reading frames is 6071 aa. Comparative sequence analysis with other serogroups of the genus Orbivirus indicated that the outer capsid protein VP2, which is the neutralizing antigen, appears to be the most variable and the major core protein VP3 is the most conserved. Overall, the structural proteins, with the exception of VP2, are more conserved than the non-structural proteins among orbiviruses. Chuzan virus is phylogenetically most related to African horsesickness virus.

Base Sequence↗

Suppression of STAT5 functions in liver, mammary glands, and T cells in cytokine-inducible SH2-containing protein 1 transgenic mice.

Various cytokines utilize Janus kinase (JAK) and the STAT (signal transducers and activators of transcription) family of transcription factors to carry out their biological functions. Among STATs, two highly related proteins, STAT5a and STAT5b, are activated by various cytokines, including prolactin, growth hormone, erythropoietin, interleukin 2 (IL-2), and IL-3. We have cloned a STAT5-dependent immediate-early cytokine-responsive gene, CIS1 (encoding cytokine-inducible SH2-containing protein 1). In this study, we created CIS1 transgenic mice under the control of a beta-actin promoter. The transgenic mice developed normally; however, their body weight was lower than that of the wild-type mice, suggesting a defect in growth hormone signaling. Female transgenic mice failed to lactate after parturition because of a failure in terminal differentiation of the mammary glands, suggesting a defect in prolactin signaling. The IL-2-dependent upregulation of the IL-2 receptor alpha chain and proliferation were partially suppressed in the T cells of transgenic mice. These phenotypes remarkably resembled those found in STAT5a and/or STAT5b knockout mice. Indeed, STAT5 tyrosine phosphorylation was suppressed in mammary glands and the liver. Furthermore, the IL-2-induced activation of STAT5 was markedly inhibited in T cells in transgenic mice, while leukemia inhibitory factor-induced STAT3 phosphorylation was not affected. We also found that the numbers of gamma delta T cells, as well as those of natural killer (NK) cells and NKT cells, were dramatically decreased and that Th1/Th2 differentiation was altered in transgenic mice. These data suggest that CIS1 functions as a specific negative regulator of STAT5 in vivo and plays an important regulatory role in the liver, mammary glands, and T cells.

Animals↗

Evaluation of the protective effects of alkaloids isolated from the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death in cultured cerebellar granule cells from rats.

We have previously shown that an aqueous extract of the hooks and stems of Uncaria sinensis (Oliv.) Havil., Uncariae Uncus Cum Ramulusis, protects against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx. Because it is not known which components of Uncaria sinensis are active, in this study we have evaluated, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) staining, the neuroprotective effects of the oxyindole alkaloids corynoxeine, rhynchophylline, isorhynchophylline and isocorynoxeine, and the indole alkaloids geissoschizine methyl ether, hirsuteine and hirsutine, isolated from the hooks and stems of Uncaria sinensis, on glutamate-induced cell death. We also investigated the inhibitory effects of the compounds on 45Ca2+ influx in cultured rat cerebellar granule cells. Cell viability evaluated by the MTT assay was significantly increased by application of rhynchophylline (10(-3) M), isorhynchophylline (10(-4)-10(-3) M), isocorynoxeine (10(-4)-10(-3) M), hirsuteine (10(-4)-3 x 10(-4) M) or hirsutine (10(-4)-3 x 10(-4) M) compared with exposure to glutamate only, with the effect of isorhynchophylline being the strongest. The increased 45Ca2+ influx into cells induced by glutamate was significantly inhibited by administration of rhynchophylline (10(-3) M), isorhynchophylline (3 x 10(-4)-10(-3) M), isocorynoxeine (3 x 10(-4)-10(-3) M), geissoschizine methyl ether (10(-3) M), hirsuteine (3 x 10(-4)-10(-3) M) or hirsutine (3 x 10(-4)-10(-3) M). These results suggest that oxyindole alkaloids such as isorhynchophylline, isocorynoxeine and rhynchophylline and indole alkaloids such as hirsuteine and hirsutine are the active components of the hooks and stems of Uncaria sinensis which protect against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx.

Alkaloids↗

Antagonism of saikosaponin-induced prostaglandin E2 release by baicalein in C6 rat glioma cells.

There are several Kampo medicines (Chinese herbal medicines) containing both Bupleuri Radix and Scutellariae Radix, which are used for the treatment of inflammation. Saikosaponins are derived from Bupleuri Radix, and baicalein is from Scutellariae Radix. The present study was undertaken to investigate the pharmacological interaction of saikosaponin b1 and baicalein in prostaglandin E2 (PGE2) release from C6 rat glioma cells in vitro. Saikosaponin a, b1 and d potently stimulated PGE2 release, while saikosaponin b2 and c moderately stimulated PGE2 release. Saikosaponin b1 caused an irreversible elevation of intracellular Ca2+ concentration, which was eliminated by removing extracellular Ca2+. On the other hand, baicalein inhibited saikosaponin b1-induced PGE2 release in a concentration-dependent manner. These results suggest that saikosaponins are activators of PGE2 release, and baicalein is one of the functional inhibitors of PGE2 release by saikosaponins.

Animals↗

Electron microscopical observations of psittacine beak and feather disease in an Umbrella cockatoo (Cacatua alba).

Psittacine beak and feather disease (PBFD) was diagnosed in an umbrella cockatoo (Cacatua alba) with severe feather dystrophy and loss. Electron microscopically, the intranuclear and intracytoplasmic inclusion bodies observed by light microscopy were composed of viral particles forming paracrystalline arrays, whorls, semicircles or concentric circles. Recovered viral particles from the skin and feather follicle tracts were icosahedral and 15 to 20 nm in diameter.

Animals↗

First isolation of Sarcocystis hominis from cattle in Japan.

Sarcocystis hominis was first isolated from slaughtered cattle raised in Japan. Cysts were 1,220-4,460 x 80-384 microns in size and their wall was 3 to 6 microns thick and appeared radially striated in the histopathological sections because of the presence of palisade-like villar protrusions on the surface. The protrusions were 3.1-4.3 x 0.7-1.1 microns in size and had many microtubules in the core. Two cynomolgus monkeys, Macaca fascicularis, fed with the Sarcocystis cysts began to pass sporocysts, which measured a size of 14.3-15 x 9.5-10 microns, in the feces 10 days after ingestion.

Animals↗

Relationship between exercise capacity and ventilatory equivalent for carbon dioxide in patients with stable old myocardial infarction.

The aim of the present study was to evaluate the relationship between exercise capacity and ventilatory response in patients with stable old myocardial infarction. We performed cardiopulmonary exercise test in 61 patients with stable old myocardial infarction and in 30 healthy men. Each subject exercised on a bicycle ergometer until exhaustion. Patients who had anginal pain or electrocardiographic ischemic changes during exercise were excluded. The patients were classified into three groups according to peakVO2 achieved during exercise, using Weber's method: group A, peakVO2 > or = 21 ml/min/kg (n = 4); group B, 14 < or = peakVO2 < 21 ml/min/kg (n = 45); and group C, peakVO2 < 14 ml/min/kg (n = 12). With progressive increases in VCO2, VE increased linearly below the anaerobic threshold (AT) level. The slope of the linear regression line between VCO2 and VE (SLOPE) was calculated in each subject. The mean SLOPE of the healthy men (group N) and groups A, B and C were 25.8 +/- 0.5, 25.1 +/- 0.5, 28.9 +/- 0.8 and 37.1 +/- 1.7 (x 10(-3), respectively. Thus, the SLOPE was steeper in patients with lower peakVO2. It is difficult to perform a maximal exercise tolerance test on patients with chronic heart failure to evaluate their exercise capacity. We can assess exercise capacity by the slope of the linear regression line between VCO2 and VE (SLOPE) at the lower exercise level.

Aged↗

Phlebosclerosis of the colon with positive anti-centromere antibody.

A 56-year-old woman with symptoms of chronic bowel disease presented a peculiar calcification of the mesenteric vein of the ascending to transverse colon on barium enema study. The resected colon was hard and black. Histo-pathologic examinations demonstrated fibrous change of the colon with a calcified and hyaline-deposited mesenteric vein. No cell infiltration was observed. These findings were compatible with phlebosclerosis and also with systemic sclerosis. Positive anti-centromere antibody and Raynaud's phenomenon, hallmarks of a variant systemic sclerosis, the CREST syndrome were observed. We therefore speculated that the pathogenesis of the phlebosclerosis of the colon is related to the CREST syndrome.

Autoantibodies↗

Anatomical changes in the pelvis after modified Chiari pelvic osteotomy.

Although plain X-ray analysis is able to reveal anatomical changes in the frontal plane of the pelvis after Chiari pelvic osteotomy involving medial displacement (medialization) in the distal fragment and lateral displacement (lateralization) in the proximal fragment, changes in the horizontal or sagittal plane can not be discerned. Here, I have investigated three dimensional changes in the pelvis using CT in 22 patients before and after Chiari pelvic osteotomy. The various changes were investigated. Medialization in the distal fragment (average 0.4 cm) occurred in the 14 cases and to a slight extent in the other 8 cases. Also anterior or posterior displacement, and anterior rotation occurred in the distal fragment. Lateralization in the proximal fragment (average 0.8 cm) occurred in 19 cases and to a slight extent in the other 3 cases. Furthermore, the acetabular coverage over the femoral head, assessed by superimposing the acetabular region over the femoral head, improved by about 30% of the anterior half of femoral head and by about 20% of the posterior half of femoral head. It is suggested that the acetabular coverage over the femoral head is most affected by lateralization in the proximal fragment.

Adult↗

Carotid artery fistula after cataract surgery.

To determine carotid cavernous fistula associated with choroidal detachment after cataract surgery. A 77-year-old woman underwent cataract surgery in both eyes. Postoperatively, proptosis and dilation of episcleral vessels in her left eye occurred and gradually increased. One month later, choroidal detachment developed in her left eye. Computed tomography showed an enlarged superior ophthalmic vein. Selected cerebral angiography showed fistulas between the megingeal branches of both the internal and external carotid arteries and the cavernous sinus. After the neurosurgical treatment, these symptoms disappeared. The development of carotid cavernous fistula after cataract surgery, as demonstrated in our patient, may be uncommon. [Ophthalmic Surg Lasers 1998;30:160-162.] Carotid cavernous fistula (CCF) is an abnormal communication between the internal carotid artery and the cavernous sinus. Ocular manifestation of the fistula includes proptosis, pulsation of the globe, orbital bruit, episcleral vein dilation, and chemosis. CCF is divided into spontaneous or traumatic by cause and direct or dural by angiographic findings. To our knowledge, CCF development after cataract surgery may be uncommon. We recently examined a patient with such a condition.

Aged↗