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Biomedical subjects

M Ohno

Publications and source records attributed to M Ohno.

At least 595 records · Page 33Linked to original sources

Malignant mesenchymoma of the esophagus.

This is a case report of a malignant mesenchymoma of the esophagus in a 50-year-old Japanese man. The tumor was a sessile polypoid mass showing a downward invasion limited to the submucosa of the esophagus. Histologically, the lesion contained rhabdomyosarcomatous and osteosarcomatous areas, in addition to an ill-defined fibrosarcomatous element. In contrast with reports of carcinosarcoma up to the present, this tumor lacked any invasive lesion of an epithelial malignancy. The morphogenesis of these tumor groups was discussed from a hamartoblastomatous standpoint.

Esophageal Neoplasms↗

Increased micrococcal nuclease sensitivity and/or solubility in nuclei from Graves' disease thyroid tissue.

The sensitivity of nuclei to micrococcal nuclease was compared in thyroid tissue obtained from euthyroid patients with solitary cold nodules and from patients with Graves' disease. A significant increase in the solubility and/or the sensitivity of nuclei to the nuclease was found in thyroid tissue from patients with Graves' disease. Electrophoretic analysis of DNA in chromatin solubilized by the nuclease revealed that the amount of oligonucleosomal DNA was increased, and that of polynucleosomal DNA was even more increased, in nuclei from Graves' thyroids than in those from normal thyroids. Polyacrylamide gel electrophoretic analysis in Triton acid-urea showed that the extent of histone acetylation in nuclei from Graves' thyroids was almost the same as in those from normal thyroids. These findings suggest that the state of chromatin organization in Graves' thyroid nuclei is different from that in normal thyroid nuclei and is independent of the extent of histone acetylation.

Acetylation↗

Tissue calmodulin levels in normal and Graves' thyroids.

Calmodulin levels in normal human thyroids and Graves' disease thyroids were measured by specific radioimmunoassay in the presence of ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). The calmodulin levels in tissues from patients with Graves' disease treated with thionamide drugs were significantly higher than those in normal tissues from euthyroid patients with solitary cold nodules (normal: 484 +/- 50 ng/mg protein, mean +/- SE, n = 15; Graves': 901 +/- 54 ng/mg protein, n = 48, p less than 0.001). Such a rise in calmodulin levels in Graves' disease thyroids was also present even after the administration of 50 micrograms of T3 for 5 days before operation (828 +/- 137 ng/mg protein, n = 6, p less than 0.01). Calmodulin levels in Graves' disease thyroids were closely related to the cell height of follicular epithelium. Calmodulin levels in a columnar cell predominant group were significantly higher than those in a flat cell predominant or a cuboidal cell predominant group (columnar cell predominant: 1150 +/- 118 ng/mg protein, n = 13; flat cell predominant: 561 +/- 125 ng/mg protein, n = 3, p less than 0.05; cuboidal cell predominant: 596 +/- 40 ng/mg protein, n = 25, p less than 0.001). The increase in calmodulin content in Graves' disease thyroid could therefore possibly be attributed to the stimulation of the thyroid gland by the thyroid stimulating antibody. An immunofluorescence study demonstrated the presence of calmodulin immunoreactivity in the thyroid epithelial cells, particularly enriched in the apical border in the form of a granulated structure.

Calmodulin↗

[HLA antigens in choriocarcinoma].

Choriocarcinoma can be regarded as transplanted cancer, because its origin is in trophoblast which is fetal tissue. It is of interest whether HLA antigens are expressed on choriocarcinoma cells or not, since HLA antigens may play an important role if the patient's body could recognize choriocarcinoma as "not self" and initiate its immune response. In this report choriocarcinoma tissue in the uterus, obtained after hysterectomy, is stained by an indirect immunofluorescence technique using monoclonal antibodies to HLA-A,B,C and HLA-DR. We believe this is the first immunohistological study in which choriocarcinoma in utero is available for study and monoclonal antibodies to HLA antigens are applied. In the staining of HLA-A,B,C, and of HLA-DR, host cells, such as myometrial cells, show positive staining but choriocarcinoma cells show negative staining. It is thought that choriocarcinoma cells are viable and show negative staining of HLA antigens, on the basis of finding following HE staining and hCG staining using anti-hCG antibody and the clinical remarks of the patient such as her high urinary hCG titer before operation and no history of chemotherapy. These results agree with those of previous studies about HLA antigens on choriocarcinoma cell lines.

Animals↗

[Oculomotor control by cerebellar flocculus studied in the monkey].

137 unitary activities were recorded from cerebellar flocculus of two pig-tail monkeys; 40 being Purkinje neurons and 81 being mossy fiber activities. Discharge patterns of these unitary activities were modulated accompanying to saccade in the dark. 11 Purkinje neurons stopped the discharge and 3 neurons and 26 mossy fibers showed burst discharges. The monkey was trained to fixate a target; 19 mossy fibers responded to the whole background sinusoidal movement, and 18 mossy fibers responded to passive head rotation. 15 mossy fibers responded to smooth target pursuit movement. 2 Purkinje neurons responded to eye position, 4 neurons responded to eye movement velocity. Responses of 3 Purkinje neurons correspond to sum of the velocity of the eye and head movements. 10 neurons respond to both position and velocity of the eye movement; response phase of 9 out of the 10 neurons changed according to the phase of the sinusoidal pursuit eye movement. The experimental results suggest that the Purkinje neurons in cerebellar flocculus of the monkey send informations concerning eye position, eye movement velocity and head movement velocity to the brain stem, thus functioning as a part of the oculomotor control system.

Animals↗

Isolation of laminin from human placental basement membranes: amnion, chorion and chorionic microvessels.

Laminin components were solubilized from basement membranes of amnion, chorion and chorionic microvessels of human placenta without prior protease digestion. These structures, after isolation, were initially processed in a sonicator bath containing a solution of Triton X-100, EDTA and 2M NaCl and the laminins extracted sequentially with 0.5M NaCl, 8 M urea, and 8 M urea + 2% 2-mercaptoethanol + 2% SDS. A high molecular weight (appr. 1 x 10(6)) complex containing laminins was purified by gel filtration on a Sepharose CL-2B column. This complex migrated as a single band on gel electrophoresis before reduction but resolved, after reduction, into four major laminin components, laminin A (350,000 M.W.), laminin M (240,000 M.W.) and laminins B1 and B2 (195,000 and 185,000 M.W.). Laminin M is a new molecular species of this protein.

Amino Acids↗

Synthetic analogues and biosynthetic intermediates of bleomycin. Metal-binding, dioxygen interaction, and implication for the role of functional groups in bleomycin action mechanism.

In order to clarify the role of bleomycin functional groups in action mechanism, the metal-binding, dioxygen activation, and DNA cleavage of several synthetic analogues and biosynthetic intermediates of bleomycin have been investigated. The present results support that 1) the beta-aminoalaninepyrimidine-beta-hydroxyhistidine portion of the bleomycin molecule substantially participates in the Fe(II) and dioxygen interactions, 2) the transposition of the pyrimidine (or pyridine) and imidazole groups in the Fe(II)-coordination is essential for the effective binding and activation of molecular oxygen by the bleomycin ligands, and 3) the gulose-mannose moiety plays an important role as an environmental factor for the efficient dioxygen reduction and DNA cleavage, although the sugar portion does not contribute significantly to the nucleotide specificity in the DNA strand scission. Certain oligopeptides are able to mimic the metal-binding and dioxygen activation by bleomycin, but not induce the effective DNA cleavage. Probably, the bithiazole DNA interaction site of bleomycin delivers the iron/dioxygen chemistry to particularly the DNA (formula, see text) nucleotide sequences.

Base Sequence↗

Postzygotic D/D translocation homozygosity associated with recurrent abortions.

A Robertsonian translocation involving homologous D chromosomes was found in two cases with a history of recurrent abortions. In the first case the propositus was a 37-year-old phenotypically normal man who had a balanced t(14q14q) translocation. In the second case, a 27-year-old phenotypically normal woman was found to be a balanced t(15q15q) translocation carrier. The recurrent abortions in both cases were probably owing to this translocation.

Abortion, Habitual↗

Synaptic changes in Purkinje cell dentritic spine of mouse cerebellum after neonatal administration of cytosine arabinoside.

This study was undertaken to elucidate morphological changes in the synaptic area of the Purkinje cell dendritic spines when granule cells were decreased in number. The mice were injected s.c. with 30 mg/kg b.w. of cytosine arabinoside on days 2, 3, and 4, and on days 7, 8 and 9, and were designated as group I and group II, respectively. The mice injected with saline on days 2, 3, and 4 served as control. The cerebella of the mice in each group were examined by electron microscopy on days 30, 60, and 90. Using photographs thus obtained, the synaptic length and area of Purkinje cell dendritic spines which participated in synapses with axons of granule cells were measured by computer. In the controls, these spines did not increase significantly either in synaptic length or in spine area in the duration from 30 to 90 days after birth. In the 90-day-old mice belonging to group I and group II, however, they increased by about 20% in the synaptic length and by about 35% in the spine area as compared to those in age-matched control. The elongation and enlargement show that the synaptic surface on the spine spreads to compensate for synapses lost by reduction in number of granule cells in experimental groups.

Age Factors↗

Orientation of a human leukocyte interferon molecule on its cell surface receptor: carboxyl terminus remains accessible to a monoclonal antibody made against a synthetic interferon fragment.

An 125I-labeled monoclonal antibody made against a synthetic 56-residue fragment of human leukocyte interferon (IFN) alpha 1 recognizes human, Escherichia coli-derived IFN alpha A bound to the surface of Madin-Darby bovine kidney cells. A major fraction of the antibody recognizes IFN specifically bound to the cells, because the number of bound antibody molecules corresponds to the number of cell-bound IFN molecules (as measured with radiolabeled ligand) and because the fraction of the IFN unspecifically bound to the cells is less than 10% of the total bound IFN. A synthetic carboxyl-terminal 16-residue IFN peptide, though not inhibiting binding of IFN to cells, inhibits binding of antibody to IFN. A recombinant IFN alpha A molecule with a carboxyl-terminal 13-residue deletion, though still able to compete for binding of IFN to cells, is not recognized by the antibody. Scatchard plot analysis of the binding data revealed apparent dissociation constants of 6.0 x 10(-10) M for the antibody-IFN interaction and of 4.0 x 10(-11) M for the IFN-cell receptor interaction. The antibody inhibits the binding of IFN to cells only weakly and neutralizes the antiviral activity of the ligand only when in a large molar excess. We conclude that the carboxyl-terminal 10-16 residues that are predicted from the cloned IFN cDNAs and that are present in some natural IFNs are not involved in binding to cells but are antigenic and hence exposed on the molecules' surface. That the carboxyl terminus is not directly involved in binding to cells is consistent with the observation that some IFNs with carboxyl-terminal deletions are biologically active.

Animals↗

Clinical usefulness of artificial endocrine pancreas "Biostator" in management of unstable diabetics.

The diurnal blood glucose profiles of 15 unstable diabetics were continuously monitored by the artificial endocrine pancreas (AEP, Biostator). Then, feedback control (FC) with the AEP was performed on each subject for 24-32 hr. Based on the data obtained from FC, the patients received an intensified conventional insulin therapy (ICIT) consisting of two daily mixed injections, 45-60 min prior to meals. There was a negative correlation between the MAGE and the sum of serum CPR in a 50 g OGTT, before FC. The M-value, MBG and MAGE decreased significantly during FC and remained lower one month later, compared with those values obtained before FC. The ICIT caused a noticeable decrease in HbA1 levels one to four months after FC. The ICIT was characterized by an increase in the proportion of short-acting insulin in the daily insulin dosage to 40. 3 +/- 11.5%. The proportion of daily insulin dosage to body weight also increased to 0.73 +/- 0.17 U/kg. These results suggest that the AEP, Biostator, could be useful in the clinical management of unstable diabetics by providing a more precise estimate of patients insulin requirements, especially those of short-acting insulin, leading to a better long-term control of blood glucose.

Adolescent↗

Enantioselective synthesis of new analogues of neplanocin A.

An efficient synthesis of analogues of (-)-aristeromycin (1) and (-)-neplanocin A (2) has been developed in an enantioselective and stereocontrolled manner by chemicoenzymatic strategy. The symmetric unsaturated dimethyl ester (3) was quantitatively hydrolyzed with pig liver esterase to yield a half ester (4). Decarboxylative ozonolysis followed by chemical transformation afforded versatile chiral intermediates, cyclopentylamine (7) and cyclopentenylamine (9), which were converted to carbocyclic analogues of 5-aminoimidazole-4-carboxamide riboside (16), (18), uridine (21), cytidine (23), and guanosine (25). The cytidine analogue (23) was found most active against KB cells in culture.

Adenosine↗

[Inhibitory effects of OK-432 and PSK on cell growth of in vitro human choriocarcinoma cell lines].

The cancer chemotherapy combined with immuno-potentiators, OK-432 and/or PSK, had yielded an improvement in survival rate of choriocarcinoma patients in our clinic as previously reported elsewhere. In the present study, for the purpose of evaluation of direct antitumor activity of OK-432 and PSK, inhibitory effects of the drugs on cell growth of GCH-1 and GCH-2 (in vitro cell lines of human choriocarcinoma) were analyzed referring to those of MTX (methotrexate) and Act-D (actinomycin D). 1) IC 50 (50% inhibitory concentration) of OK-432 and of PSK were 0.56 KE/ml on GCH-1 and 0.48 KE/ml on GCH-2, and 310 micrograms/ml on GCH-1 and 460 micrograms/ml on GCH-2, respectively. 2) The morphological changes of the target cells, observed by light and electron microscope, induced by OK-432 and PSK seemed to be not different from those by MTX and Act-D. 3) Serial changes of hCG levels in the culture media in which OK-432 or PSK was added were roughly comparable with those in MTX or Act-D. Thus, the direct antitumor activity of OK-432 and PSK on GCH-1 and GCH-2 was exquisitely weak judging from their IC50 and it was suggested that their direct antitumor effects in vivo might be clinically negligible in choriocarcinoma.

Animals↗