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Biomedical subjects

H Sakaguchi

Publications and source records attributed to H Sakaguchi.

446 records · Page 25Linked to original sources

Voltage-gated Na+ channel EOIII-segment-like immunoreactivity in fish retinal ganglion cells.

Although single-channel and whole-cell patch-clamp recordings have demonstrated the presence of Na+ currents in retinal ganglion cell somata, it has not previously been reported that an anti-Na+-channel antiserum stains both retinal ganglion cell somata and proteins with molecular weights corresponding to complexes of alpha and beta subunits. We probed adult goldfish retinas for Na+ channel-like immunoreactivity with a polyclonal antibody directed against the EOIII segment of vertebrate voltage-gated Na+ channels. In vertical sections and whole mounts, this antibody consistently stained the somata, axons, and proximal dendrites of retinal ganglion cells. Some somata in the proximal third of the inner nuclear layer were also stained. In Western blots, this antibody specifically stained multiple protein bands from retina and optic nerve, all with apparent molecular weights between 200 and 315 kDa. The largest of these molecular weights agrees with that reported previously for complexes of alpha and beta subunits in mammalian neurons, including retinal ganglion cells. The intermediate and lowest molecular weights are consistent with the presence of multiple Na+ channel alpha subunits, either in individual proximal retinal neurons or in different morphological subtypes.

Animals↗

Detection of the preneoplastic lesions of small hepatocellular carcinoma in cirrhotic livers.

To identify the preneoplastic lesions of hepatocellular carcinoma and the fine structure of preneoplastic hepatocytes, we studied proliferative conditions in cirrhosis of the liver. In all, 46 foci of cellular alteration (FCA), three regions of adenomatous hyperplasia (ADH), and 21 small hepatocellular carcinomas (sHCC) were studied by published criteria for sHCC and by the proliferative activity of the lesions as examined with monoclonal antibodies against DNA polymerase alpha and proliferating cell nuclear antigen. The four patients with FCA composed of basophilic hepatocytes were classified by the criteria as having sHCC; cells had features similar to those of sHCC. Two of these four patients with FCA were found to have HCC several years later. The number of hepatocytes stained for proliferating cell nuclear antigen was 72 and 81 per 1000 hepatocyte nuclei in the two patients who developed HCC. In one of the three patients with ADH, a sHCC was found 1 year later, and dysplastic hepatocytes from the region of ADH in this patient had features similar to those of HCC cells by light and electron microscopy. In this patient, the number of hepatocytes stained for DNA polymerase alpha was 452 per 1000 nuclei. Therefore, FCA and ADH might be preneoplastic lesions of sHCC in cirrhosis of the liver. Preneoplastic hepatocytes seem to be small cells with basophilic cytoplasm, with a large nucleus to cytoplasm ratio, finely indented nuclei with a smaller amount of condensed chromatin than normal, and poorly to moderately developed organelles.

Aged↗

Alpha-fetoprotein subfractions in germ cell tumors identified by Con A or LCH crossed-line affinity immunoelectrophoresis.

Using concanavalin A (Con A) crossed-line affinity immunoelectrophoresis and lentil lectin (LCH) crossed-line affinity immunoelectrophoresis, alpha-fetoprotein (AFP) subfractions were studied in sera including three sera from nude mice heterotransplanted with human yolk sac tumor of the ovary and three sera from patients with yolk sac tumor, mature solid teratoma, or immature solid teratoma of the ovary. In sera of nude mice bearing yolk sac tumor or from a patient with yolk sac tumor, subfractions from yolk sac and those from fetal liver were identified. Since AFP subfractions from yolk sac and fetal liver can be differentiated according to the carbohydrate moieties, our findings indicate that AFP produced by yolk sac tumor and fetal yolk sac are to some extent differently glycosylated. We also found that AFP produced by yolk sac tumor and fetal yolk sac are to some extent differently glycosylated. We also found that AFP in both mature and immature solid teratoma was composed of two subfractions ontogenetically originating from yolk sac or fetal liver. All these findings indicate that more than two different factors are responsible for the AFP synthesis in germ cell tumor of the ovary.

Adult↗

Expression of size-polymorphic androgen receptor gene in uterine leiomyoma according to the number of cytosine, adenine, and guanine repeats in androgen receptor alleles.

The amino terminus region of the androgen receptor (AR) gene in the X chromosome involves the cytosine, adenine, and guanine (CAG) repeats. Random X chromosome inactivation with AR alleles in individual cells occurs in females. Therefore, probably either paternal or maternal single dominant polymorphic AR mRNA must be expressed in neoplastic tissue originating from monoclone. This prompted us to determine the deviated numbers of CAG repeats in AR mRNA to understand the clonality of uterine leiomyoma. A solitary node of leiomyoma was macroscopically found in 7 cases, and multiple nodes were found in another 23 cases. Homozygous CAG repeats (22.0 +/- 2.3) in AR alleles were found in 5 of 30 cases, and either a large or small size of AR mRNA expression, were found in individual nodes of uterine leiomyoma, although paternal and maternal AR mRNAs from normal uterine myometrium were consistently expressed as AR alleles. There was no significant specificity in activated AR alleles related to CAG numbers in individual nodes. Therefore, an individual node of uterine leiomyoma might be formed from an independent monoclonal uterine leiomyoma cell.

Adenine↗

Electrocochleography in deaf subjects.

Electrocochleography using the transtympanic electrode technique was performed on 86 deaf ears. Auditory nerve action potential was detected in 9 ears, in 5 of which deafness was caused by cerebellopontine angle tumor or surgery. A low threshold of the cochlear microphonics' response was also observed in some of the cases with deafness caused by mumps or cerebellopontine angle tumor. Various pathophysiological states of the inner ear can be observed, even in cases showing the same total deafness when measured by audiometer.

Acoustic Stimulation↗

Secretory IgA in saliva and academic stress.

Several reports have proposed that the concentration of secretory immunoglobulin A (S-IgA) in saliva is an indicator of psychological stress. With this in mind, we decided to examine it in 10 second year medical student volunteers at Kawasaki Medical School course between May 4 and July 13, 2000 and discussed the relationship between S-IbA and the stress from academic examinations. Saliva was collected three times (on rising, at forenoon, and at bedtime) every Thursday. During this period, sporadic academic examinations were held twice and term end examination occurred during the last two weeks. Results showed the concentration of S-IgA significantly higher at the on rising time-point than at the other two time-points. There was also a tendency for the S-IgA level in saliva to be higher on the day before academic examinations and during them and lower on the days between these examinations. In addition, daily variations in the S-IgA concentration sometimes seemed to be disturbed by other academic stress. Therefore it may be possible to use this measurement to monitor psychological stress in students and workers.

Adult↗

Reduced function of CD4+25+ regulatory T cell fraction in silicosis patients.

The quality and quantity of CD4+25+ regulatory T cells (Treg) in silicosis patients (SIL) were examined and compared with results from healthy donors (HD) because SIL often develop autoimmune diseases along with pulmonary disorders. Peripheral blood mononuclear cells from 57 SIL and 50 HD were analyzed for Treg. Treg frequency and clinical parameters were subjected to a factor analysis. Treg and CD4+25- T cells (Tneg) from five HD and five SIL, sorted by flow-cytometer, were used for functional assays of Treg, the expression pattern of Treg specific genes (FoxP3, GITR and CTLA-4) and activation-related genes (CD122 and CD123). Although the actual frequency of Treg did not differ between SIL and HD, the age-corrected level was reduced in SIL. The factor analysis showed that Treg frequency was positively associated with the serum level of IL-2. The inhibitory effect of Treg on Tneg activation was decreased when the Treg:Tneg ratio was 1:1/4 to 1/2. In addition, Treg dominancy of FoxP3 and CTLA-4 expression and Tneg dominancy of CD132 expression found in HD were lost in SIL. These results indicated that the Treg fraction in SIL may be substituted with chronically activated T cells due to recurrent exposure to silica, resulting in a reduction in the frequency and function of Treg. Since the reduction of Treg may precede the clinical manifestation, as silicosis may be a pre-clinical status for autoimmune diseases, control of Treg function using cell and/or gene therapy may be a good way to manage autoimmune disease.

Aged↗

Takayasu's arteritis with heart failure due to atherosclerosis.

An autopsy case of an elderly man with Takayasu's arteritis and atherosclerosis is presented. Ischemic signs and symptoms including anginal attack were aggravated with activity of arteritis despite administration of prednisolone throughout the entire course. The autopsy revealed severe atherosclerosis over the aorta and its branches, and arteritis in the fibrotic stage in localized area. Vessels of vital organs including heart and kidneys, did not show Takayasu's arteritis but were atherosclerotic. This case highlights the numerous problems encountered in the treatment of elderly patients with vasculitis such as Takayasu's arteritis.

Aged↗

Effect of the nitrosourea anti-tumor chemotherapeutical agent MCNU on five human myeloma cell lines.

We investigated the effects of MCNU (methyl-6)3-(2-chloroethyl)-3-nitrosoureido)-6-deoxy- alpha-D-glucopyranoside), a nitrosourea anti-tumor agent developed in Japan, on cell growth and differentiation in five human myeloma cell lines and compared it with relative expression levels of MDR-1 gene. Although 10 microg/ml of MCNU inhibited cell growth in KMM-1 and KMS-5 lines, other three cell lines required 20-40 microg/ml of MCNU to obtain similar growth inhibition. Accumulation up to the G2 phase of the cell cycle was observed in KMM-1 and KMS-5 lines and the cloning efficiency of KMS-5 cells was reduced by MCNU. On the other hand, expression of surface markers on these lines was not altered remarkably except for increased expression of CD38 on KMS-5 cells. However, the effect of MCNU on these cell lines did not correlate to relative expression levels of MDR-1 gene analyzed by RT-PCR. MCNU may inhibit the growth of myeloma cells by the accumulation of these cells up to the G2 phase, but may not affect their differentiation.

Antineoplastic Agents↗

Ultrasonographic evaluation of portal blood flow using transhepatic carbon dioxide injection.

BACKGROUND/AIMS: The evaluation of portal blood flow in hepatic mass is important for the diagnosis of hepatocellular carcinoma. We have designed a new method to easily evaluate portal blood flow in hepatic mass using ultrasonography with injection of carbon dioxide into the intrahepatic portal vein by direct puncture with a fine needle. METHODOLOGY: We evaluated 29 masses in the liver of 20 patients ultrasonically with injection of carbon dioxide into the intrahepatic portal vein. RESULTS: Of 29 space-occupying lesions (SOLs), 13 were found to have portal blood flow and 16 were found to have no portal flow by this method. All 15 SOLs which had no portal flow were histologically confirmed to be hepatocellular carcinoma. Of 13 SOLs with portal flow, 5 were confirmed to be hepatocellular carcinoma. For 7 of 9 SOLs in which both this method and arterial portographic computed tomography were performed, the results were in agreement. CONCLUSIONS: Ultrasonographic evaluation of portal blood flow using transhepatic carbon dioxide injection appears to be useful for the evaluation of portal flow in mass and may aid in the diagnosis and management of mass in patients with liver disease.

Adolescent↗

Establishment and characteristics of human hepatocellular carcinoma cells with metastasis to lymph nodes.

BACKGROUND/AIMS: Although the mechanism of cancer metastasis has been gradually elucidated, less is known concerning the characteristics of human hepatocellular carcinomas (HCCs) with metastatic potential. We examined the expression of molecules that mediate cell-cell or cell-substrate interaction, nm23-H1 expression, and ultrastructural features of several human HCC cell lines. METHODOLOGY: Expression of E-cadherin, integrin (alpha3beta1), intracellular adhesion molecule-1 (ICAM-1), and nm23-H1 protein was analyzed by immunocytochemistry or Western blotting, and ultrastructural features were further studied by electron microscopy in 4 human HCC cell lines, PLC/PRF/5, HuH-7, OCUH-16, and Nuk-1 which were originally established from metastatic cells in lymph nodes at our institute. RESULTS: Neither E-cadherin, integrin, nor ICAM-1 was immunocytochemically detected in any of the 4 cell lines. Expression of nm23-H1 protein was weakly detected in OCUH-16, Nuk-1, and Huh-7 cells by Western blotting, but was clearly detected in PLC/PRF/5 cells by Western blotting. Ultrastructurally, metastatic Nuk-1 cells exhibited the intracytoplasmic canaliculus-like structures found in fibrolamellar carcinoma and the intracytoplasmic glandular lumina found in bile-duct carcinoma, while the other 3 cell lines did not. In addition, Nuk-1 cells expressed neither cytokeratin 8 nor cytokeratin 19. CONCLUSIONS: Nuk-1 cells, which are human HCC cells with metastasis to lymph nodes, alone exhibited intracytoplasmic canaliculus-like structures and glandular lumina, as well as a marked reduction of nm23-H1 protein, but did not express E-cadherin, integrin, or ICAM-1. Formation of both intracytoplasmic canaliculus-like structures and intracytoplasmic glandular lumina is one of the characteristics that may be involved in metastasis of HCC cells to lymph nodes, as is reduction of nm23-H1 protein.

Biomarkers, Tumor↗

Eosinophils are neither migrated nor activated in the skin lesions of atopic dermatitis in infants.

Eosinophils and eosinophil cationic protein (ECP) were examined in the skin lesions of 10 infants with atopic dermatitis (aged 4 months to 7 years). In all 10 patients, neutrophils and eosinophils were rarely seen in these lesions. Moreover, in the immunohistochemical study, ECP was scarcely detected in any of them. Our results suggest that eosinophils are neither migrated nor activated in the skin in atopic dermatitis in infants.

Blood Proteins↗

Transjugular intrahepatic portosystemic shunt in combination with oral anticoagulant for Budd-Chiari syndrome.

The antiphospholipid antibody syndrome is characterized by arterial and venous thrombosis including hepatic veins. Although transjugular intrahepatic portosystemic shunt or liver transplantation have been considered for Budd-Chiari syndrome, treatment options for patients with complete obstruction of three hepatic veins including the junction with the inferior vena cava are limited. We describe a 27-year-old female, who suffered thrombotic obliteration of hepatic veins including the portion confluent with the inferior vena cava (Budd-Chiari syndrome) associated with marked ascites and liver dysfunction. Transjugular intrahepatic portosystemic shunt using a Wall-stent (10 mm in diameter) between inferior vena cava and intrahepatic portal vein was performed. Intrastent coagulation and recurrence of thrombosis were prevented by combination therapy with warfarin potassium and ticlopidine hydrochloride. These treatments induced loss of ascites and improvement of liver function, and she has been able to resume daily life. The portosystemic shunt described above in addition to combination therapy with warfarin potassium and ticlopidine hydrochloride appeared to be one of the options for treating Budd-Chiari syndrome associated with antiphospholipid antibody syndrome.

Adult↗

Afterloading intracavitary irradiation and expanding stent for malignant biliary obstruction.

A double lumen catheter was developed as an applicator for the remote afterloading (RALS) of 60Co source for the intracavitary irradiation of an obstructed common bile duct caused by carcinoma of the gallbladder. This was followed by the placement of nylon-covered expandable metallic stents to maintain patency. This combination effectively provided palliation.

Brachytherapy↗