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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 559 records · Page 31Linked to original sources

The novel insulinotropic mechanism of pimobendan: direct enhancement of the exocytotic process of insulin secretory granules by increased Ca2+ sensitivity in beta-cells.

Pimobendan is a new class of inotropic drug that augments Ca2+ sensitivity and inhibits phosphodiesterase (PDE) activity in cardiomyocytes. To examine the insulinotropic effect of pimobendan in pancreatic beta-cells, which have an intracellular signaling mechanism similar to that of cardiomyocytes, we measured insulin release from rat isolated islets of Langerhans. Pimobendan augmented glucose-induced insulin release in a dose-dependent manner, but did not increase cAMP content in pancreatic islets, indicating that the PDE inhibitory effects may not be important in beta-cells. This agent increased the intracellular Ca2+ concentration ([Ca2+]i) in the presence of 30 mM K+, 16.7 mM glucose, and 200 microM diazoxide, but failed to enhance the 30 mM K+-evoked [Ca2+]i rise in the presence of 3.3 mM glucose. Insulin release evoked by 30 mM K+ in 3.3 mM glucose was augmented. Then, the direct effects of pimobendan on the Ca2+-sensitive exocytotic apparatus were examined using electrically permeabilized islets in which [Ca2+]i can be manipulated. Pimobendan (50 microM) significantly augmented insulin release at 0.32 microM Ca2+, and a lower threshold for Ca2+-induced insulin release was apparent in pimobendan-treated islets. Moreover, 1 microM KN93 (Ca2+/calmodulin-dependent protein kinase II inhibitor) significantly suppressed this augmentation. Pimobendan, therefore, enhances insulin release by directly sensitizing the intracellular Ca2+-sensitive exocytotic mechanism distal to the [Ca2+]i rise. In addition, Ca2+/calmodulin-dependent protein kinase II activation may at least in part be involved in this Ca2+ sensitization for exocytosis of insulin secretory granules.

Androstadienes↗

Electron microscopic observations on sperm penetration in cytochalasin-treated eggs of the rose bitterling.

The effects of cytochalasin B (CB), which acts on microfilaments, on sperm penetration into eggs of a teleost fish were investigated ultrastructurally. Eggs from the rose bitterling, Rhodeus ocellatus ocellatus, were pre-treated in physiological saline containing CB and inseminated in water also containing CB. Microvilli at the sperm entry site (SES) under the micropyle disappeared or shortened in length following CB treatment. However, a spermatozoon attached to and fused with the SES of CB-treated eggs. The spermatozoon present in a swollen mass (SM) remained at the egg surface even after membrane fusion and did not enter the cortex. It was unclear whether or not sperm movement from the cortex to the inner cytoplasm is CB-sensitive. The SM formed and plugged the micropyle. CB did not inhibit cortical alveolus breakdown. Based on the present experiments with fish eggs, it is concluded that CB inhibits sperm movement from the egg surface to the cortex, but not sperm attachment (binding), membrane fusion and SM formation during the process of sperm penetration.

Animals↗

Lymphatic drainage of the cerebrospinal fluid from monkey spinal meninges with special reference to the distribution of the epidural lymphatics.

The structural organization of the epidural lymphatics and lymphatic drainage of the cerebrospinal fluid from spinal meninges was studied in Japanese monkeys (Macaca fuscata) by an enzyme-histochemical method. The spinal meninges were examined at various intervals from 1 to 48 h, as well as at 30 days, following an injection of ultrafine carbon particles into the subarachnoidal space (cisterna magna). Lymphatics were differentiated from blood capillaries by the 5'-nucleotidase (5'-Nase)-alkaline phosphatase (ALPase) double staining method (KATO et al. 1991, 1993) both in the whole-mount preparations and tissue sections. Carbon-filled collecting lymphatics and lymph nodes constantly appeared in the cervical and thoracic regions but only rarely in the lumbo-sacral region after carbon injection. Networks of 5'-Nase-positive lymphatics in the epidural connective tissues were seen in a large area on the dorsal surface around each spinal nerve root in the cervical and upper thoracic regions, especially at a level corresponding to the brachial plexus (C5-Th1). Carbon particles were often found within the 5'-Nase-positive lymphatics. In the lower thoracic and lumbo-sacral regions, on the other hand, the epidural lymphatic network covered only a small area around each spinal nerve root. These findings suggest that the epidural lymphatics are well developed on the dorsal side of the lower cervical spinal dura mater and may function as an absorptive pathway for the cerebrospinal fluid from the subarachnoidal space.

Animals↗

Lymphatic network and nerve plexus in the myenteric layer of the monkey jejunum: a topographic study using an enzyme-histochemical method.

The topographic relationship between the lymphatic network and the nerve plexus in the myenteric layer of the monkey jejunum was studied by an enzyme-histochemical method. Identification of the lymphatics was achieved by a 5'-nucleotidase staining method, and the enteric neural components were visualized by acetylcholinesterase staining. A well-developed lymphatic network and a dense nerve plexus were demonstrated throughout the myenteric layer. Numerous segments of the initial lymphatics, with their blind endings at the apical parts, tended to gather toward the ganglion and run along the primary nerve strands. Elements of the tissue interstitium separated the lymphatics from the enteric nerves. Nerve terminals were often located closely beneath the endothelium of the initial lymphatics and were exposed to the subendothelial tissue on the side facing the abluminal surface of the lymphatic endothelium. These findings suggest that the lymph flow in the initial lymphatics might be regulated by the enteric nervous system, and that the transport of tissue fluid by the lymphatics might serve as a suitable microenvironment for the enteric nerves.

Animals↗

Temporal lobe epilepsy associated with cerebral venous angioma--case report.

A 21-year-old male presented with temporal lobe epilepsy associated with a venous angioma in the ipsilateral frontal lobe, presenting as intractable complex partial seizures. Neuroimaging showed a cerebral venous angioma in the right dorsolateral and opercular frontal lobe, and atrophy of the right hippocampus. As the ictal electroencephalogram (EEG) obtained with subdural electrodes indicated spike discharges initiating from the right mesial temporal lobe, temporal lobectomy was performed. The patient was seizure-free after the operation. Patients with epilepsy who have a cerebral venous angioma require precise analysis of the seizure pattern and an ictal EEG because of cerebral venous angioma may be associated with an another epileptogenic lesion which is surgically treatable.

Adult↗

Clinicopathologic study of multiple primary superficial carcinoma of the esophagus.

Endoscopic examination with iodine staining has led to the easy detection of multiple superficial esophageal carcinoma (MSEC). The purpose of this study was to better understand the characteristics of MSEC. Of 49 patients with multiple esophageal carcinomas, 19 had superficial carcinoma. Multiple esophageal carcinomas were more often found in superficial carcinomas (31.1%) than in advanced carcinomas (14.4%). Comparing the depth of invasion of multiple esophageal carcinomas, the secondary lesions represented relatively early stages. Ki-67-positive cells were seen significantly more frequently in the main lesion of MSEC than in the secondary lesions, but proliferating cell nuclear antigen positivity and p53 expression did not differ significantly. Since multiple carcinoma occurs more frequently, care should be taken to look for small secondary lesions when treating superficial esophageal carcinoma. Ki-67 immunohistochemistry suggested that tumor cells proliferate more slowly in secondary lesions than in main lesions of MSEC.

Antibodies, Monoclonal↗

Fibroblast growth factor-2 and -9 regulate proliferation and production of matrix metalloproteinases in human gliomas.

Fibroblast growth factor (FGF) signaling has been recognized in human gliomas. We tested the effect of FGF-2 and FGF-9 on the proliferation and the expression of matrix metalloproteinases (MMPs) and their inhibitor (TIMP-1) in vitro. Both FGFs showed mitogenic activity on U251MG and NMC-G1 cells. MMP-1 expression and collagenolytic activity of NMC-G1 but not of U251MG, and TIMP-1 expression of both cells were stimulated by FGFs. MMP-2 expression, gelatinolytic activity, and chemoinvasion on the matrigel were not altered. FGFs may regulate proliferation and microenvironmental factors independently in each glioma type.

Brain Neoplasms↗

A case of acquired zinc deficiency in a mature breast-fed infant.

We describe a 5-month-old Japanese infant with zinc deficiency, who was exclusively breast-fed and showed improvement after zinc supplement was administered. His serum zinc level and the zinc content of breast milk from his mother were extremely low, although the mother's serum zinc level was within normal limits. Zinc deficiency would not be latently uncommon in a mature breast-fed infant.

Alopecia↗

Detection of APC mutations by a yeast-based protein truncation test (YPTT).

APC gene mutations play a role in the initiation step of colorectal carcinogenesis in both familial adenomatous polyposis (FAP) and non-FAP patients. Almost all of the APC mutations are nonsense or frameshift mutations, which truncate the APC protein and are thought to inactivate normal APC function. We show a novel method for detecting nonsense and frameshift APC gene mutations by using Saccharomyces cerevisiae. Polymerase chain reaction (PCR)-amplified APC fragments are cloned directly into yeast expression vectors in vivo, and the yeast expresses a hemagglutinin epitope (HA)-tagged APC peptide. When an APC fragment contains a nonsense or frameshift mutation, HA-tagged truncating APC peptide can be detected by Western blotting using an anti-HA antibody. We identified both germ-line and somatic APC mutations in patients with FAP and non-FAP colorectal tumors, respectively. This method, called the yeast-based protein truncation test (YPTT), is simple and fairly cheap, and it can be applied to any genes that are inactivated by protein truncating mutations.

Adenomatous Polyposis Coli Protein↗

Immunohistochemical localization of thyroid hormone nuclear receptors in human hair follicles and in vitro effect of L-triiodothyronine on cultured cells of hair follicles and skin.

To investigate the cellular basis of the action of thyroid hormone on hair follicles, we studied the immunohistochemical localization of thyroid hormone receptors (TRs) in human scalp skin using a mouse monoclonal antibody, TR alpha 1 (C4) against TRs. Immunoreactive TRs were detected in the nuclei of the outer root sheath cells (ORSCs), dermal papilla cells (DPCs), fibrous sheath cells of hair follicles, hair arrector pili muscle cells and sebaceous gland cells. However, nuclei of hair matrix cells were not clearly stained with TR alpha 1 (C4). The epidermis showed positive nuclear staining by the antibody. Ductal and secretory portions of eccrine sweat glands were also stained with the antibody as we had expected. In the dermis, almost all the cell components including fibroblasts, vascular endothelial and smooth muscle cells, and Schwann cells were positively stained. Immunofluorescence also showed TRs expression in cultured ORSCs, DPCs, epidermal keratinocytes and dermal fibroblasts. L-triiodothyronine stimulated the proliferation and/or metabolism of all these four types of cells significantly, although there was variation at the rate of stimulation. Whereas, structurally similar, but metabolically inactive analog, reverse T3 had no effect. These results demonstrate the presence of thyroid hormone nuclear receptors in human hair follicles. Furthermore, the presence of TRs in different cell types in the skin suggests numerous direct effects of thyroid hormone on this target tissue.

Animals↗

[Psychopathological study on "hallucination of soliloquy" in a case of schizophrenia].

We present what appears to be the first reported case of schizophrenia with hallucinatory soliloquy. An appropriate name for this symptom might be "hallucination of soliloquy." A thirty-year-old man had been laboring under delusions of persecution and auditory hallucinations in the form of being blamed by others after changing his job at the age of twenty-eight. He consulted our hospital because of unintentional "soliloquy." He complained that he had been maltreated in his new work place and that this stress made him talk to himself. The contents of his "soliloquies" were nonsensical; for example, he would grumble about his colleagues or the plot of a teleplay that he had seen the previous day. During his "soliloquies" he had the vivid sensation of both speaking and hearing his own voice, but the episodes actually lacked vocalization. As a result of therapy, the patient's disorder gradually shifted from "soliloquy" to "silent soliloquy," then to "breathing hard," before finally disappearing. We are aware of a similar symptom, "delusion of soliloquy" (Y. Kasahara et al.), in which the patient believes that he unintentionally spoke to himself and that everyone learned his secrets through his soliloquy. In comparison, our "hallucination of soliloquy" is unique in that it is an abnormal experience of both speaking and hearing. From the viewpoint of traditional symptomatology, "hallucination of soliloquy" is composed of auditory hallucinations, which are experiences of hearing, and psychomotor hallucinations, which are experiences of speaking. In other words, it is a simultaneous experience of both thought resonance and "hallucination verbale psychomotrice" (J. Séglas) or "Halluzination des Muskelsinns" (A. Cramer) of the speech apparatus. However the overall concept of "hallucination of soliloquy" deviates from both thought resonance and "hallucination verbale psychomotrice" or "Halluzination des Muskelsinns." For a different point of view, we refer to L.S. Vygotsky's studies on inner speech. A comparison of "hallucination of soliloquy" with inner speech suggests that "hallucination of soliloquy" is "inner speech which is converted into outer speech" or "egocentric speech without vocalization." S. Kato notes that two patterns are found in the schizophrenic discourse, mirroring discourse and deviant discourse, which are named after mirroring and deviant characters concerning the ordinary linguistic code. The former simulates the ordinary linguistic code. In mirroring discourse, the patient almost literally imitates and repeats customary discourse such as an authority's speech or television. The latter is characterized by deviation from human actuality or the existing linguistic code and is represented by delusions, neologisms, and incoherent speeches. It has been suggested that mirroring discourse has moments of return to actuality, while in deviant discourse the patient remains entirely in the delusional world. It is said that discourse is realized in the deviant mode in the case of ordinary auditory hallucinations. In the case of "hallucination of soliloquy," the discourse occurs in the patient's own mind and is spoken through his own mouth, in short, it is realized in mirroring mode. We conclude that "hallucination of soliloquy" has the characteristic of mirroring discourse, which is realized in mirroring mode. We suggest that "hallucination of soliloquy" is schizophrenic auditory hallucination that has self-healing moments.

Adult↗

DNA topoisomerase: the key enzyme that regulates DNA super structure.

DNA is a macromolecule carrying all genetic information and it must be packed in the cell nucleus. DNA is a double helix where one strand coils around the other. The helix is unwound and rewound every now and then to take out its information, which requires local alteration of the helical structure, resulting in the super-coiling of DNA. For replication, all the coils must be unwound at least once, and two daughter molecules are often catenated to each other. To solve these problems caused by the helical structure of DNA, topoisomerase activity introducing the transient breaking and rejoining of DNA strand is essential to perform each DNA transaction. In this article, we first review the mechanistic aspect of topoisomerase activity, and then discuss its basic clinical importance.

Adenosine Triphosphate↗

A plaque hybridization assay for quantifying and cloning infectious human immunodeficiency virus type 1 virions.

A biological method was developed for quantifying and cloning of infectious virions of human immunodeficiency virus type 1 (HIV-1). Virus preparations were mixed with permissive cells for binding, and the cells were cast in an agarose gel. After incubation for 9 days viral particles released from infected cells propagating from each initially infected cell were transferred on nylon membrane and subjected to hybridization using a radioactive HIV-1 DNA probe. Infectious centers of HIV-1 were detected as hybridization spots on autoradiographs regardless of cytopathic effects or syncytium formation. Three different CD4+ cell lines (MT-4, MOLT-4 and U937) and peripheral blood mononuclear cells from healthy donors were used as recipient cells. Infectious virions were recovered from a portion of agarose gel corresponding to each hybridization spot. This assay is suitable for quantifying infectious HIV-1 virions with different cell tropisms and for investigating the relationship between the phenotype and genotype of HIV-1 at a clonal level.

Cell Line, Transformed↗

Biological properties of kinin-releasing enzyme from Trimeresurus okinavensis (himehabu) venom.

A kinin-releasing enzyme was isolated and characterized from the venom of Trimeresurus okinavensis (himehabu) using Sephadex G-100, DEAE-Cellulose, and CM-Cellulose column chromatographies. The kinin-releasing enzyme was homogeneous as demonstrated by a single band on polyacrylamide gel electrophoresis, and isoelectric focusing. The enzyme possesses a molecular weight of 31,000 Da and isoelectric point of 8.2 and consists of 312 total amino acid residues. Specific esterolytic activities of the kinin-releasing enzyme on N-tosyl-L-arginine methyl ester (TAME) and N-benzoyl-L-arginine ethylester (BAEE) were determined to be 235.3 and 111.3 mumol/min/mg, respectively. The enzyme was inhibited by p-APMSF (p-amidinophenylmethanesulfonyl fluoride hydrochloride) and benzamidine. Additionally, the enzyme was found stable to heat treatment. The enzyme cleaved a kininogen analog with the release of bradykinin, resulting in an immediate drop in blood pressure, and contractions of the rat uterus were also observed.

Animals↗