Biomedical subjects
Publications and source records attributed to M Ohno.
MR images of four patients with a thickened filum terminale showing a fat signal are presented. There were no related symptoms and no evidence of tethering. The thickened fatty filum terminale seemed to be a developmental anomaly and without clinical significance. As the incidence of this anomaly was 0.24% in our series, knowledge of its possible presence of this anomaly is important for routine reviews of MR image.
Serial magnetic resonance (MR) imagings of two autopsied patients with Creutzfeldt-Jakob disease (CJD) are presented. Both patients showed a dramatic progression of brain atrophy. The initial MR imagings were, however, interpreted as normal except for localized mild cortical atrophy in one patient. When a normal MR image is obtained in a demented middle-aged or aged patient, CJD may still need to be ruled out: follow up MR imaging may be useful.
The results of chromosome studies on cultured umbilical cord blood lymphocytes from a consecutive series of 14,835 liveborn infants (7,608 males and 7,227 females) are described. Ninety-three infants (6.27 per 1,000) had a major chromosome abnormality. Of these, thirty-one infants (2.09 per 1,000) had sex chromosome abnormalities. Seven male infants had a 47,XXY karyotype, five had a 47,XYY karyotype, and three were mosaics. One male had a ring Y chromosome in all cells examined. A pericentric inversion of the Y chromosome was found in one case. Seven female infants had a 47,XXX karyotype, one had a 45,X karyotype and six were mosaics. Sixty-two infants (4.18 per 1,000) had autosomal abnormalities. There were twenty-one infants with trisomy 21 including one mosaic, six infants with trisomy 18, and two infants with trisomy 13 of a Robertsonian translocation type. Three infants had an unbalanced derivative chromosome resulting from a parental reciprocal translocation. Two infants with a partial monosomy of chromosome 13 were detected. There were four infants carrying an additional small marker chromosome. Twenty-four infants (1.62 per 1,000) had a balanced structural rearrangement of the autosomes; eleven with a Robertsonian translocation, eleven with a reciprocal translocation, and two with a pericentric inversion. The incidence of each type of major chromosome abnormality in this study was quite similar to that obtained from previous newborn surveys.
Two phospholipases A2, named phospholipases A2-I and A2-II, were purified to homogeneity from the venom of Trimeresurus gramineus (green habu snake). The complete amino acid sequence of phospholipase A2-I was determined by sequencing the native protein and the peptides produced by enzymatic (Achromobacter protease I, clostripain, and chymotrypsin) and chemical (hydroxylamine) cleavages of the S-pyridylethylated derivative of the protein. The protein consisted of 122 amino acid residues and was similar in sequence to phospholipases A2 from the venoms of crotalid snakes which belong to the category of Group II. A most striking feature of this protein is that tyrosine at the 28th position which is common in phospholipases A2 and is assumed to be a part of the Ca2(+)-binding loop is replaced by phenylalanine. Such replacement is the first finding in Group II phospholipases A2. Secondary structure compositions of phospholipase A2-I are similar to those of Crotalus atrox phospholipase A2. No appreciable Ca2(+)-induced difference spectrum was observed, due probably to the absence of the effective chromophoric groups in the neighborhood of the Ca2+ binding site although Ca2+ is bound with affinity similar to that for T. flavoviridis phospholipase A2.
The possible occurrence of congenital hydrocephalus by viral infection of the mother was examined by inoculating pregnant hamsters intravenously with parainfluenza virus type 3 (PIV-3). We could produce congenital hydrocephalus in littermates born to a mother which had been inoculated into the left cervical vein on the 14th day of pregnancy. This result may indicate that the virus could pass through the placenta to arrive at the fetus, and infect the central nervous system.
The authors report a case of Werner's syndrome complicated by quintuplicate malignancy, and review the literature data. Four malignancies occurred synchronously in the case: osteosarcoma of the left distal tibia, malignant melanoma of the left plantar region, gastric cancer, pulmonary coin lesion. The osteosarcoma and malignant melanoma were treated by below-knee amputation and the gastric cancer by palliative surgery; the pulmonary coin lesion did not respond to cisplatin chemotherapy. It was difficult to treat the multiple primary cancer curatively, and patient died of respiratory failure due to a brain tumor seven months after surgery. The postmortem examination revealed a papillary carcinoma of the thyroid gland and a leiomyosarcoma of the lung. In some cases of Werner's syndrome, attention should be paid to the concurrent occurrence of multiple primary malignant neoplasms.
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A simplified method of coronary angiography was performed by means of the percutaneous transbrachial approach with a 5-F catheter designed for selective cannulation of the right and left coronary arteries. On 70 serial coronary angiograms, visualization of the coronary arteries was sufficient in all cases with no major complication. The preformed catheter required only simple manipulation. This method was easy, safe, and rapid in the investigation of coronary artery disease.
Bromohydrins (12, 13, and 14), which were oxidatively damaged products of thymidine nucleotides, were repaired by the action of sunlight (2700 lux) or heat via a radical mechanism to regenerate the original nucleotides (8,9, and 10). A significant effect of 3',5'-phosphate linkage on the repair reactions to natural type of thymidine nucleotide was proposed.
The clinical features of acute myocardial infarction patients in whom abnormal Q wave disappeared were analyzed. Of 201 patients, 40 (20%) (Group A) showed disappearance of Q wave in serial electrocardiograms. Regional ejection fraction of the infarcted portion improved significantly (from 24 +/- 2 to 34 +/- 4%, p less than 0.001) during chronic phase in Group A, but no such improvement was present in Group B patients who showed no change in the Q wave. Global ejection fraction was greater and percent akinetic segment was smaller in Group A than in Group B at chronic phase. Coronary occlusion occurred more often at segment 7 in Group A; in Group B, occlusion occurred more frequently upstream at segment 6, suggesting Group A had a smaller area of risk. Spontaneous recanalization was more often (57%) and complete occlusion was less frequent in Group A. These indicate that Group A is characterized by a smaller area of risk, smaller infarct size, earlier reperfusion, and greater improvement in wall motion. Twenty-eight patients (70%) of Group A lost Q wave within one month and 12 patients (30%), after 3 months or more. Electrical stunning of the myocardium may be a possible mechanism for the early disappearance of Q waves, and anatomical healing for the late disappearance of Q waves.
The behavioral and EEG effects of the 5-HT1A partial agonist ipsapirone were investigated to determine its pharmacological characteristics as an anxiolytic drug in rats, mice and rabbits, as compared with those of buspirone and diazepam. 1) The anticonflict effect of ipsapirone was almost equipotent as that of buspirone and less potent than that of diazepam in rats. Ro15-1788 antagonized the anticonflict effect of diazepam, but did not that of ipsapirone. 2) Muricide in midbrain raphe-lesioned and olfactory bulbectomized rats was inhibited by ipsapirone. However, the inhibition of muricide by ipsapirone was attenuated by its repeated administration. 3) The muscle relaxant effects of ipsapirone and buspirone on rotarod performance were less potent than that of diazepam. Ethanol-induced muscle relaxation was markedly potentiated by diazepam, but less potently by ipsapirone and buspirone. 4) The pentetrazol-induced convulsion was dose-dependently antagonized by diazepam, while it was weakly potentiated by ipsapirone and buspirone. 5) The limbic afterdischarges induced by either hippocampal or amygdaloid stimulation in rabbits were markedly inhibited by diazepam. Conversely, ipsapirone and buspirone slightly potentiated afterdischarges. In conclusion, it is suggested that ipsapirone has anxiolytic activities similar to that of buspirone and moderate antimuricidal action. In addition, ipsapirone, like buspirone, is also characterized by its less potent muscle relaxant, alcohol-potentiating and anticonvulsant actions.
Differences from normal in microsomal antigen (M-Ag) may be involved in the development of autoimmune thyroid disease. We compared the M-Ag in Graves' thyroid immunologically and biochemically to that in normal thyroid. The concentration of M-Ag, measured with an enzyme-linked immunosorbent assay, was significantly greater in the Graves' microsomes than in normal microsomes. Binding of a patient's microsomal antibody to Graves' microsomes was completely inhibited when the serum was first incubated with normal thyroid microsomes. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and Western blotting were done with a monoclonal antibody to denatured M-Ag. In both Graves' and normal thyroids, M-Ag existed as 107-, 101-, and 95-kDa peptides. After incubation with V8 protease, the residual antigenic peptide had a molecular weight of less than 60,000 and after incubation with trypsin, 95- and 87-kDa peptides and several smaller antigenic peptides were found. There were no significant differences in the pattern of normal and Graves' microsomes after digestion. Two-dimensional gel electrophoresis of Graves' microsomes showed that the isoelectric point for the 107-kDa peptide was at pH 7.2; that for the 101-kDa peptide was at pH 6.2, and that for the 95-kDa peptide was at 6.5. These values were not different from those observed for normal microsomes. These results indicate that M-Ag in Graves' thyroid does not differ from that in normal thyroid, and that microsomal antibodies in autoimmune thyroid disease probably do no arise from differences in the antigen.
We have reported that some anti-thyroid peroxidase antibodies inhibit the activity of thyroid peroxidase in vitro. These thyroid peroxidase activity-inhibiting immunoglobulins seem to inhibit thyroid function in some patients, but the relationship between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function is not simple. We designed this study to explore this lack of a simple relationship. We stained immunoglobulin G deposits by immunofluorescence staining or the peroxidase-antiperoxidase method, and stained endogenous thyroid peroxidase activity by enzyme histochemistry in thyroid sections. When cryostat thyroid sections were incubated with thyroid peroxidase activity-inhibiting immunoglobulins, immunoglobulin G deposits were seen as lines of stain on the apical border and as intracellular staining, and endogenous thyroid peroxidase activity was inhibited. In paraffin-embedded thyroid sections from 5 Hashimoto's patients and 6 Graves' patients, immunoglobulin G deposits were not found on the apical border of the follicular epithelium. In frozen thyroid sections from 22 Graves' patients, no clear deposits of immunoglobulin G on this apical border were seen. In organ-cultured thyroid slices incubated with thyroid peroxidase activity-inhibiting immunoglobulins, endogenous thyroid peroxidase activity was not inhibited. In conclusion, thyroid peroxidase activity-inhibiting immunoglobulins may reach its antigen only with difficulty. This is one of the reasons why no simple relationship is observed between thyroid peroxidase activity-inhibiting immunoglobulins and thyroid function.
Intact human laminin and laminin type IV collagen complexes were extracted from term placental membranes and their structures were examined by electroimmunoblot and by rotary shadowing electron microscopy. Rotary shadowing electron microscopy revealed a structure of human laminin which is essentially similar to the cruciform structure of the mouse tumor (EHS) laminin, but with some notable differences. The observed lengths of the short arms in the human laminin are different. One short arm has an average length of 34 nm and another short arm a length of 42 nm. In the mouse laminin all three short arms are of equal length. The average length of the long arm is 97 nm, which is longer than that of mouse tumor laminin (77 nm). The distal portion of the long arm has two clearly separated globular domains instead of the single one observed with tumor laminin. Human laminin was found in various states of aggregation including dimers, trimers and higher aggregates. Laminin molecules appeared to attach to a point in type IV collagen located 87 nm from C-terminus, or at 174 nm from C-terminus and one with less frequency, at 251 nm from C-terminus. A small number of molecules appeared to bind at the N-terminus of the collagen. These laminin-collagen interactions occurred via the distal globular domains of both the short and long arms of laminin. The data suggest that human laminin extracted from placenta is structurally different from that isolated from the mouse EHS tumor.
A suitable procedure for the production of human monokines was defined as 'differentiation-induction' culture. Human monocytic leukemia THP-1 cells were well-differentiated from nonfunctional promonocytes into macrophage-like cells by the induction with a combination of mezerein, retinoic acid, and a Mycoplasma fermentans extract. The differentiated THP-1 cells secreted a high amount of macrophage differentiation-inducing factor (DIF) activity and concomitantly produced other known monokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta), into the medium. These results suggest that other novel human monokines may also be found in the conditioned medium of THP-1 cells induced by the 'differentiation-induction' culture conditions defined in this study. Macrophage DIF was purified to homogeneity and NH2-terminal amino acid sequence analysis revealed that macrophage DIF is very similar or identical to human leukemia inhibitory factor (LIF). The cDNA encoding human LIF was isolated using the polymerase chain reaction, and a clone producing 3.7 micrograms/10(6) cells day recombinant LIF was selected from Chinese hamster ovary (CHO) cells which were transfected with the LIF cDNA. The recombinant LIF production in CHO cells was quantified using MTT reduction assay with M1 cells.
To assess the diagnostic value of Tc-99m PYP, Tl-201 dual isotope SPECT for the evaluation of myocardial viability, segmental comparison between dual isotope SPECT and exercise, delayed, and reinjected Tl study were performed with 18 AMI patients. Among 72 damaged myocardial segments, 48 segments (67%) were judged as viable by chronic phase Tl studies. The segments with severely reduced Tl uptake by dual SPECT showed significantly lower prevalence of viable myocardium than the segments with reduced and normal Tl uptake (p less than 0.001). The segments with PYP accumulation localized to the subendocardium represented the favorable outcome compared with the transmural accumulation (p less than 0.001). And overlap segments show better prognosis than the segments without overlap (p less than 0.05). Most importantly, we can get better predictive accuracy of myocardial scar by dual isotope SPECT than the judgement by Tl or PYP SPECT alone (83.3% vs 77.8%, 68.1%). Thus, we conclude that Tc-99m PYP, Tl-201 dual isotope SPECT is useful to assess the severity of myocardial damage in the acute phase of myocardial infarction.
To characterize B cell hyperactivity in autoimmune NZB/NZW (B/W) F1 mice, we studied the effects of murine recombinant interferon gamma (IFN-gamma) on interleukin 4 (IL-4) induced resting B cell growth and differentiation. The number of resting B cells of B/W F1 mice were decreased, with more sensitivity to IL-4 than normal mice. Thus, resting B cell hyperresponsiveness to IL-4 was in a dose-dependent manner suppressed by IFN-gamma. This action was most noticeable when IFN-gamma was added to the culture system simultaneously with IL-4. As well, IFN-gamma did not exhibit cytotoxicity. These results suggest that IFN-gamma may have regulatory effects on IL-4 mediated B cell triggering.
Trimeresurus flavoviridis phospholipase A2 (PLA2) induced strong contractions of the smooth muscles of guinea pig ileum and artery in a concentration-dependent manner (10(-10)-10(-6) M). When the same dose of PLA2 was administered in repetition to the ileal preparation, the contraction diminished progressively and was no longer recovered even by consecutive washings. The enzymatically inactive derivative of PLA2, in which His-47 was p-bromophenacylated, was unable to elicit contraction. Also, no activity was observed when the Ca(2+)-free medium was used. The contraction induced by PLA2 was inhibited completely by 1.0 x 10(-6) M indomethacin, but not by nordihydroguaiaretic acid. These results imply that the PLA2-induced contraction is due essentially to the hydrolytic action of the enzyme against phospholipid membranes to liberate arachidonic acid that is then converted to pharmacologically active prostaglandins. In guinea pig artery, PLA2 caused both contraction and relaxation.