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Biomedical subjects

T Ohno

Publications and source records attributed to T Ohno.

At least 775 records · Page 43Linked to original sources

Morphological studies of peripheral nerves and skeletal muscles of an adult case with adrenoleukomyeloneuropathy.

A 53-year-old patient with adrenoleukomyeloneuropathy, showing symptoms of mental deterioration, cerebellar ataxia, spastic tetraparesis, and polyneuropathy, was reported. The myelinated fiber densities were decreased in the anterior spinal root and sciatic nerve. Most of the myelinated fibers showed segmental demyelination and a few fibers showed axonal degeneration. Electron microscopy showed numerous lipid inclusions in the cytoplasm of the Schwann cells. The muscles showed neurogenic changes. Numerous lipid bodies and intracytoplasmic crystalline arrays were found in the sarcolemma.

Adrenoleukodystrophy↗

Use of a murine monoclonal antibody for detection of circulating plasma DF3 antigen levels in breast cancer patients.

The murine monoclonal antibody (MAb), designated DF3, reacts with a 300,000-mol wt mammary epithelial antigen. A sequential double-determinant radioimmunoassay (RIA) has been developed to monitor circulating DF3 antigen. Using this assay, we have demonstrated that 33 of 36 normal women had plasma RIA antigen levels less than 150 U/ml. In contrast, 33 of 43 patients (76%) with metastatic breast cancer had RIA DF3 antigen levels greater than or equal to 150 U/ml. The difference between these two groups was statistically significant (P less than 0.001). Similar results have been obtained with a double-determinant enzyme-linked immunoassay (EIA). Only 6 of 111 age-matched normal subjects had EIA DF3 antigens levels greater than or equal to 30 U/ml, while 42 of 58 patients (72%) with breast cancer had levels equal to or above this value. Thus, similar patterns of specificity are obtained with the EIA or RIA. The elevation of circulating DF3 antigen levels in breast cancer patients has been confirmed by transfer blot assays. MAb DF3 reactivity occurred predominantly with circulating antigens of three different molecular weights ranging from 300,000 to approximately 400,000 mol wt. We also demonstrate that patients with both primary and metastatic breast cancer who were free of detectable disease at the time of sampling have DF3 antigen levels that are similar to those obtained from normal subjects. While patients with hepatoma (27%) and ovarian carcinoma (47%) also had elevated circulating DF3 antigen levels, the results suggest that DF3 antigen levels may be useful in distinguishing breast cancer patients from those with esophageal, gastric, colorectal, pancreatic, and lung carcinomas. Furthermore, the results of the RIA, EIA, and transblot analyses demonstrate that the measurement of circulating DF3 antigen levels provides a new and potentially useful marker to follow the clinical course of patients with metastatic breast cancer.

Adult↗

Circulating DF3 and CA125 antigen levels in serum from patients with epithelial ovarian carcinoma.

The murine monoclonal antibody (MAb), designated DF3, reacts with a 300-kilodalton (kd) mammary epithelial antigen. A sequential double-determinant enzyme-linked immunoassay (EIA) has been developed to monitor circulating DF3 antigen. Previous studies have demonstrated that the use of the DF3 EIA provides a new and potentially useful marker to follow the clinical course of patients with metastatic breast cancer. In the present study, we have monitored circulating DF3 antigen in the serum of patients with epithelial ovarian carcinomas and non-ovarian gynecologic malignancies. Twenty-one of 45 patients (47%) with ovarian carcinoma had elevated DF3 antigen levels (greater than or equal to 30 U/mL). In contrast, three of 20 patients (15%) with non-ovarian gynecologic malignancies, and only four of 59 control women (7%) had elevation of circulating DF3 antigen. The difference between DF3 antigen values from patients with ovarian cancer and from controls was significant (P less than .001). The elevation of circulating DF3 antigen in ovarian cancer patients has also been confirmed by transblot assays. MAb DF3 reactivity occurred predominately with circulating antigens of molecular weights (mol wt) ranging from 300 to 450 kd. Furthermore, DF3 antigen levels have been shown to correlate with progression of disease in six patients with ovarian cancer and after resection of disease in two others. The half-life of circulating DF3 antigen was approximately 45 to 60 days. The results also demonstrate that DF3 antigen is distinct from CA125, a glycoprotein associated with coelomic epithelium and developmental amnion. The use of both the DF3 EIA and the immunoradiometric assay previously described to detect circulating CA125 suggests that determining levels of both markers may enhance the sensitivity of monitoring the course of ovarian cancer. Furthermore, the use of both assays may be useful in distinguishing ovarian cancer from other malignancies.

Adult↗

[Clomiphene-HMG ovarian stimulation in human in vitro fertilization and embryo transfer].

In a program for in vitro fertilization and embryo transfer, laparoscopies for oocyte aspiration were performed in 40 cycles in 36 normally menstruating women with irreparable tubal diseases (IVF patients) who received clomiphene citrate (CC) and human menopausal gonadotropin (hMG). An intramuscular injection of human chorionic gonadotropin (hCG) was given to all patients after completion of follicular maturation. Fourteen cycles in 13 spontaneously ovulating women (control patients), also stimulated with CC and hMG, were adequately monitored to identify the appearance of the spontaneous luteinizing hormone (LH) surge. The follicular maturation was followed by daily ovarian ultrasonographic examination and serum estradiol estimations. Just before the LH surge the diameter of the leading follicle was 20.2 +/- 0.7 (mean +/- S.E.) mm and the serum estradiol concentration per follicle was 384.1 +/- 16.3pg/ml in the control patients. In the IVF patients the former was 20.6 +/- 0.3mm and the latter was 305.8 +/- 13.3pg/ml prior to hCG administration. When the relationship of follicular size to the rates of oocytes recovery, maturation, fertilization and cleavage was examined, larger follicles (3ml less than or equal to follicular fluid volume) showed good results. Of the 152 oocytes that were recovered from these IVF patients, 96 (63.2%) were fertilized and 79 (52.0%) cleaved. Three pregnancies resulted from 35 embryo transfers.

Adult↗

Purification and characterization of a high molecular weight glycoprotein detectable in human milk and breast carcinomas.

The murine monoclonal antibody (MAb) designated DF3 has defined a high m.w. antigen detectable in human breast carcinomas and in human milk. DF3 antigen is detectable on apical borders of secretory mammary epithelial cells and in the cytosol of less differentiated malignant cells. DF3 antigen expression has been shown to correlate with the degree of human breast tumor differentiation, and the detection of a cross-reactive species in human milk has suggested that DF3 antigen might be useful as a biochemical marker of differentiated mammary epithelial cells. To further characterize DF3 antigen, we have developed an approach to purify the cross-reactive species by using gel filtration and antibody affinity chromatography. The affinity column-purified DF3 antigen was absorbed by wheat germ agglutinin and peanut agglutinin, but not by concanavalin A or lentil lectin. In contrast, wheat germ agglutinin inhibited MAb DF3 reactivity with the purified antigen, whereas there was little, if any, inhibition when using peanut agglutinin. These findings are thus consistent with the involvement of terminal N-acetyl-D-neuraminic acid and/or N-acetylglucosamine residues in the antigenic site. DF3 antigenicity was also sensitive to neuraminidase, but not chondroitinase ABC, chondroitinase AC, chondroitin-4-sulfatase, or hyaluronidase. Furthermore, DF3 antigen was sensitive to Pronase, subtilisin BPN', and alpha-chymotrypsin. The presence of O-glycosidic linkages between carbohydrate and protein in the DF3 antigenic site was further supported by the presence of NaBH4-sensitive sites. Together, these results suggest that sialyl oligosaccharides present on a peptide backbone are required for maintaining DF3 antigenicity. Similar findings have been demonstrated for DF3 antigen purified from both human milk and breast cancer effusions. However, the DF3 antigen in human milk consisted of a single high m.w. species, whereas the tumor-associated antigen consisted of two distinct glycoproteins with m.w. of 330,000 and 450,000. These findings may be relevant to the recent demonstration that distinct high m.w. DF3 antigens are elevated in the circulation of patients with breast carcinoma.

Antibodies, Monoclonal↗

Multiple receptor types for amino acids in the carp olfactory cells revealed by quantitative cross-adaptation method.

A quantitative method of cross-adaptation was developed to explore the difference in the receptor sites for various amino acids in the carp olfactory receptors. The olfactory responses were measured by recording the stimulant-induced waves from the olfactory bulb. Cross-adaptation was carried out by varying concentrations of amino acids in a wide range. Typical examples of the results obtained are as follows. The response to Thr after Ser was decreased with increasing concentration of Ser applied first and reached the spontaneous level, while that to Thr after Glu was decreased to 77% of the level of the original response with increasing Glu concentration and stayed this constant level with a further increase in Glu concentration. Application of the amino acids in the reverse order gave essentially similar results. Such types of experiments were carried out between various pairs of amino acids. The results obtained suggested that amino acids of very close species (e.g. Thr and Ser, Asp and Glu, Tyr and Phe) stimulate the same respective receptor sites and that amino acids of most other pairs stimulate more or less different receptor sites, although there exist the receptor sites stimulated commonly by both amino acids of one pair. It was concluded that the carp olfactory cells have many different receptor sites stimulated only by one species of amino acid and its close analogues.

Animals↗

Nucleotide sequence of cucumber pale fruit viroid: homology to hop stunt viroid.

Double stranded cDNA of cucumber pale fruit viroid ( CPFV ) has been cloned by the method of Okayama and Berg (Mol.Cell.Biol.2,161-170 (1982] and the complete nucleotide sequence was established. The covalently closed circular molecules of single-stranded CPFV RNA consists of 303 nucleotides. The nucleotide sequence of CPFV was compared with the previously established sequence of hop stunt viroid (HSV), which consists of 297 nucleotides ( Ohno et al. Nucleic Acid Res.11,6185-6197 (1983]. CPFV differs from HSV in the nucleotide sequence at 16 positions which include 8 exchanges, 7 insertions and 1 deletion. Both viroids share about 95% sequence homology. Considering the pathogenic properties of both viroids together, it is concluded that CPFV is a cucumber isolate of HSV.

Base Sequence↗

Antigen-independent leukocyte random locomotion inhibitory activity in human ultrafiltrated leukocyte extracts.

Human ultrafiltrated leukocyte extracts (MW less than 5000) were fractionated by Sephadex G-10 column chromatography and the effects of these fractions on leukocyte random locomotion were investigated in vitro. Fr-4, one of these fractions, had significant leukocyte random locomotion inhibitory activity, independent of the presence of mononuclear leukocytes. This inhibitory activity was not due to cytotoxic effects on leukocytes. As seen by scanning electron microscopy, the number of cell surface pseudopods on leukocytes incubated with Fr-4 was reduced. Fr-4A, one of three fractions separated from Fr-4 by Sephadex G-25 column chromatography, significantly inhibited leukocyte random locomotion. Fr-4A contained numerous components, one of which was identified as 2-deoxyribose, on the basis of thin-layer chromatography. Biologically 2-deoxyribose showed an inhibitory effect on leukocyte locomotion and a reduction of the extrusion of pseudopods on the surface of leukocytes, at the range of assayed concentrations. This inhibitory activity is probably derived from 2-deoxyribose.

Antigens↗

Efficacy of several plasma components in a young boy with chronic thrombocytopenia and hemolytic anemia who responds repeatedly to normal plasma infusions.

This report describes a patient with thrombocytopenia, microangiopathic hemolytic anemia, proteinuria, and microscopic hematuria that could be transiently improved by the infusion of plasma or various plasma components. An increase in platelet count following the transfusion of normal plasma was predictable and reproducible. In therapeutic trials with commercially available plasma components, factor VIII preparations were effective for inducing an increase in the platelet count and improving hemolytic anemia, but albumin, gamma-globulin, factor IX, and fibronectin preparations were ineffective. Serum from normal donors also relieved the symptoms of this condition in our patient. Partial plasma exchange (1,000 ml/m2 of body surface area) was performed with albumin instead of normal plasma, but there was no significant effect on platelet count or anemia. Large, multimeric von Willebrand factor components of the factor VIII complex (VIII/vWF) were found in the patient's plasma when his platelet count was normal, but their levels were reduced when the platelet count was decreased. The multimers of the patient's plasma were larger than those in normal plasma, but smaller than those in normal platelet lysate. Although the pathogenesis of this disease remains unknown, we conclude that transfusions of normal plasma, serum or factor VIII concentrate provide a factor that causes significant improvement in the thrombocytopenia and hemolytic anemia. Furthermore, large VIII/vWF multimers are possibly directly involved in pathogenesis of this disease.

Anemia, Hemolytic, Congenital↗

Adrenoleukodystrophy: a clinical variant presenting as olivopontocerebellar atrophy.

A case of adrenoleukodystrophy showing neurological features of olivopontocerebellar atrophy is described. A CT scan demonstrated marked atrophy in both cerebellum and pons. ACTH stimulation produced no rise in the plasma cortisol level but a significant rise in the plasma aldosterone level. The ratios of C26:0 to C22:0 in fatty acids of sphingomyelin from erythrocyte membrane and plasma were increased.

Adrenocorticotropic Hormone↗

A revised replication cycle for viroids: the role of longer than unit length RNA in viroid replication.

Longer than unit length plus and minus strand RNAs were detected in hop stunt viroid (HSV) infected cucumber leaf tissues by Northern blot hybridization analysis using strand-specific probes. To elucidate the role of these longer than unit length RNAs in the viroid replication cycle, we synthesized tandemly repeated plus and minus strand HSV RNAs in vitro from cloned HSV cDNA and assayed their infectivities. Two and four unit tandemly repeated plus strand RNAs were infectious, but one unit plus, and one, two and four unit minus strands were noninfectious. Taking these data into consideration, we propose a revised rolling circle model for viroid replication.

Cloning, Molecular↗

Cross adaption between stress and cold in rats.

Three-hour immobilization stress was imposed on male adult rats of Wistar strain by restraining them on a board 6 days a week for 1-8 weeks. The stressed rats showed less body weight gain during the experiment compared to the controls. These stressed animals manifested an improved cold tolerance as shown by no significant fall in colonic temperature in the cold at -5 degrees C for 300 min during the experimental period, while the colonic temperature of the controls fell progressively. Nonshivering thermogenesis as assessed by noradrenaline-induced increase in oxygen consumption was significantly potentiated in the stressed rats. The weight and protein content of the intercapsular brown adipose tissue (BAT) increased and BAT mitochondria were more packed in the stressed rats. Plasma insulin, insulin/glucagon molar ratio and thyroxine levels were lowered in the stressed rats, while the plasma triiodothyronine level remained unchanged. Removal of interscapular BAT led to a loss of improved cold tolerance and a significant reduction of nonshivering thermogenesis in the stressed rats. These results indicate that repetitive stress may induce cross adaptation between stress and cold through an enhanced capacity of nonshivering thermogenesis mediated, at least in part, via stimulation of BAT function.

Adaptation, Physiological↗