Biomedical subjects
K Iijima
Publications and source records attributed to K Iijima.
[Surgical treatment of pseudoaneurysm of the left ventricle after myocardial infarction--a case report].
A 62-year-old woman had myocardial infarction with congestive heart failure. Follow-up chest X-rays showed progressive prominent bulging of the left cardiac silhouette. Echocardiography revealed a large echo-free space behind the posterior of the left ventricle. Magnetic resonance imaging and left ventriculogram confirmed the huge pseudoaneurysm of the left ventricle. We performed the operation 4 months later the onset of the myocardial infarction. The pseudoaneurysm was opened under cardio-pulmonary bypass. It contained a large amount of old thrombi and communicated with the left ventricle through several orifices in the inferior left ventricular wall. The orifices were closed primarily with pledged mattress and running sutures. The aneurysmal wall was left unresected. The pathologic study showed no myocardial element nor endocardium in the aneurysmal wall. Postoperative course was uneventful, and she discharged from the hospital in a healthy condition.
Chemocytoarchitecture of the rat locus ceruleus.
I shall elaborate on the cytochemical classifications of the rat locus ceruleus (LC) and state how each of these could be identified. In the LC, 80% (1,309/1,642) of the noradrenergic (NA) neurons are also GABAergic. This is found by demonstrating that two immunoreactivities coexist in adjacent sections alternately immunostained by anti-TH or anti-GABA antibody. Pharmacological manipulations with pargyline (75 mg/kg, i.p., 2 h prior to perfusion) and L-tryptophan (150 mg/kg, 1.5 h prior to perfusion) revealed 5-HT-like immunoreactivity (5-HT-LI) in most LC cells (masked 5-HT cells) that produce 5-HT but not other indoleamines. If 5-HTP is applied instead of tryptophan, 5-HT-LI is shown by the raphe nuclei and a few LC cells (masked indoleamine cells) in the marginal zone. Anti-GAD antibody reveals GAD-LI in 32% of GABA neurons predominantly in the dorsal division. In situ hybridization studies detected tryptophan hydroxylase mRNA and GAD mRNA in many small- and medium-sized neurons. It is concluded that the LC consists mostly of an NA population that is possibly synthesizing multiple transmitters, such as GABA, GAD and 5-HT in single neurons so that the system enables the LC simultaneously to innervate the entire CNS.
[Blood coagulation-fibrinolysis tests by a biochemical method].
Blood coagulation-fibrinolysis factors are conventionally measured using fibrinogen or fibrin as a natural substrate. With recent advances in the technology to biochemically separate and purify, individual coagulation-fibrinolysis factors were isolated and purified, and their biochemical properties, function, and primary structure were clarified. Measurement techniques for blood coagulation-fibrinolysis factors were also developed. At present, enzyme activity for each factor is measured by the synthetic substrate method, on the other hand trace proteins and complex proteins are measured using monoclonal antibody. We present an outline of blood coagulation-fibrinolysis factors and synthetic substrates, and describe the characteristics of the synthetic substrate method using measurement of plasma tissue factor and protein C activity as examples.
[A clinicopathologic study of thymomas: a review of 52 cases, with particular reference to results of treatment].
Clinicopathologic aspects of 52 thymomas were reviewed. Masaoka staging revealed stage I in 32, stage II in 2, stage III in 12, stage IV a in 3, and stage IV b in 3. Eleven patients (21%) had associated myasthenia gravis (MG), and three (6%) had pure red cell aplasia (PRCA). Operation was complete resection in 39 patients (stage I 32, stage II 2, stage III 2, and stage IV b 3), subtotal resection in 4 patients (stage III 2, stage IV a 2), partial resection or simple biopsy in 7 patients (stage III 6, stage IV a 1). Survival rates at 5 years and 10 years were 88%, 88% in noninvasive thymomas, and 65%, 45% in invasive thymomas, respectively. Statistical analysis indicated that patients with noninvasive thymomas had significantly longer survival than those with invasive thymomas. Significant difference was not found in survival on the basis of tumor cell type according to lymphocyte/epithelial cell ratio. Associated MG had no influence on the survival of thymoma patients, however, the presence of PRCA was an adverse factor in survival. In cases of invasive thymomas, there was statistically significant difference in the survival rates between the group of patients undergoing complete or subtotal resection and the group undergoing partial resection or only biopsy. Irradiation was of value in local control of thymoma, but lymphogeneous or hematogeneous recurrence occurred in 21% of patients with invasive thymomas from 3 months to 12 years postoperatively. Lifelong follow-up should be necessary in thymoma patients since late recurrence is not so rare.
An abnormal protein C (protein C Yonago) with an amino acid substitution of Gly for Arg-15 caused by a single base mutation of C to G in codon 57 (CGG-->GGG). Deteriorated calcium-dependent conformation of the gamma-carboxyglutamic acid domain relevant to a thrombotic tendency.
Protein C Yonago is a dysfunctional protein C characterized by defective anticoagulant activity determined by a coagulation assay and normal amidolytic activity measured on a synthetic substrate S-2366 (Iijima et al., Thromb Res 1991;63:249-257). We have identified a single point mutation of C to G in codon 57 (CGG-->GGG) of the gene for protein C Yonago by genetic analysis utilizing the polymerase chain reaction. The mutation should have resulted in an amino acid substitution of Gly for Arg at position 15 of the light chain of mature protein C. No mutations were found in nucleotides spanning the putative gamma-carboxylase recognition site or gamma-carboxyglutamic acid residues of protein C. Protein C Yonago was non-reactive to monoclonal antibodies JTC-1 and -3 that solely recognized the calcium-dependent conformation of the gamma-carboxyglutamic acid domain. This indicated that the mutation had critically perturbed the highly conserved structure of the gamma-carboxyglutamic acid domain. Thus, the calcium-dependent conformation required for the phospholipids binding to exert the physiological functions of protein C may not have been elicited normally in this abnormal protein C, resulting in defective generation of anticoagulant activities in plasma. Consequently, no anticoagulant activities may have been generated in vivo.
[Attitudes toward handicapped children--a study comparing parents of handicapped children and others, in the case of Down syndrome].
The physically handicapped have received increasing attention in recent years. Since 1981, the International Year of Handicapped Persons, a number of administrative measures have been passed and the rights of handicapped have been recognized. However some problems still remain. In this study, conducted in 1990, the knowledge people have about congenital defects and their thinking regarding the social system for the handicapped were examined. A similar survey of parents of children with congenital defects was conducted to understand problems they encountered in the medical care and education of their child. Eighty-four parents of Down Syndrome children (DS) and 118 controls including housewives, female office workers, and students were surveyed. Results showed that 44% of mothers of DS wanted their husbands to participate more intensively in the medical care and education of their child. A slight gap in knowledge between the parents and the controls was seen. Of the controls, 12% asserted that the relationship of the handicapped and the non-handicapped should be equal. However, some of controls expressed that if they had a child with congenital defects, they had no confidence that they could bring up the child in this society.
Immunocytochemical and in situ hybridization evidence for the coexistence of GABA and tyrosine hydroxylase in the rat locus ceruleus.
We have demonstrated the coexistence of GABA-like and tyrosine hydroxylase-like immunoreactivities (GABA-LI and TH-LI, respectively) in the same neurons of the rat locus ceruleus (LC). The profiles of these cells were labeled by alternately immunostaining adjacent sections for GABA-LI or TH-LI by the avidin-biotin-peroxidase complex method or the peroxidase-anti-peroxidase method after perfusion (either Zamboni's fixative or PPG), and observation at light and electron microscopic levels. For light microscopy, pairs of adjacent sections of more than 590 (Zamboni's) and 260 (PPG), and for electron microscopy, 40 ultrathin sections cut from adjacent semithin plastic sections (Zamboni's), were examined. GABA-LI was found in 80% (1,309/1,642 in total) of small and medium-sized neurons, uniformly scattered throughout the LC. Observations unequivocally show that the majority of GABA-ergic neurons are also noradrenergic. Several neurons are neither noradrenergic nor GABA-ergic, while other noradrenergic neurons do not show GABA-LI. It is shown that astrocytes, but not oligodendrocytes, contain GABA. In situ hybridization using a probe DNA fragment of the glutamic acid decarboxylase (GAD) cDNA, amplified by the polymerase chain reaction, detected GAD mRNA signals in many neurons throughout the LC, supporting the presence of a GAD/GABA system in the LC. Multiple "classical" transmitters, including GABA, serotonin, and noradrenaline, coexist in many LC neurons and may contribute to its widely diverging projections throughout the entire CNS.
Regulation of cytoplasmic calcium concentration in tetracycline-treated osteoclasts.
The ability of low-dose tetracyclines to inhibit collagenase activity and inactivate osteoclasts suggests that these compounds have great potential as a prophylaxis for metabolic bone disease. However, the cellular mechanism by which tetracyclines interact with skeletal tissue is not yet clear. To better understand the effects of tetracyclines on bone metabolism, we examined their effect on osteoclast activity in vitro. Because tetracyclines can enter the cell and bind calcium and have been reported to directly interact with osteoclasts, we postulated that exposure to either of two tetracyclines, minocycline or doxycycline, would alter cytosolic Ca2+ regulation in rat osteoclasts. [Ca2+]i was measured in single rat osteoclasts utilizing fura-2. Addition of extracellular Ca2+ (5 mM CaCl2), a potent osteoclast inhibitor, increased [Ca2+]i in all osteoclasts, but 10(-6) M salmon calcitonin (sCT) did so only in a subpopulation of osteoclasts. Neither minocycline nor doxycycline (10 micrograms/ml) altered steady-state osteoclast [Ca2+]i. Further, neither minocycline nor doxycycline pretreatment affected the sCT-mediated increases in [Ca2+]i. However, tetracycline pretreatment significantly decreased the cytosolic Ca2+ response to extracellular CaCl2. Our results strongly suggest that tetracyclines have a specific effect on extracellular Ca(2+)-stimulated cytosolic Ca2+ mobilization in osteoclasts, which is not solely dependent on their ability to buffer Ca2+. Furthermore, these results point to the potential use of tetracyclines as probes to study cytosolic Ca2+ regulation. However, that tetracyclines attenuate a signal response associated with decreased osteoclastic resorption suggests that the reported antiresorptive attributes of tetracyclines must be achieved independently of an effect on osteoclastic cytosolic Ca2+.
Effect of phototherapy on sister-chromatid exchange in infants with Down syndrome.
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Effect of He-Ne laser irradiation on synaptic transmission of the superior cervical sympathetic ganglion in the rat.
The effect of low-power He-Ne laser on synaptic transmission was studied in the superior cervical sympathetic ganglion of Wistar rats. Extracellular and intracellular recordings were made from isolated ganglia before and after laser irradiation. In addition, effects of ganglion irradiation on skin blood flow were observed in in vivo preparations. Irradiation on the isolated ganglion decreased the amplitude of evoked compound action potentials in the extracellular recordings. Intracellular recordings from ganglion cells revealed that the neuronal membrane was hyperpolarized, while threshold potential and latency of response were unchanged. The reduction of skin blood flow during preganglionic nerve stimulation lessened by irradiation on the ganglion. Our results indicate that low-power He-Ne laser depresses sympathetic ganglionic transmission, and hyperpolarization of ganglionic cells takes part in the mechanism of action.
Attenuation of endothelin effects by a chloride channel inhibitor, indanyloxyacetic acid.
We have recently proposed that the actions of endothelin (ET) are in part mediated by opening of chloride channels (K. Iijima, L. Lin, A. Nasjletti, and M. S. Goligorsky. Am. J. Physiol. 260 (Cell Physiol. 29: C982-C992, 1991). In the present study the ability of a chloride channel inhibitor, an indanyloxyacetic acid (IAA-94), to block ET-induced effects was examined in cultured vascular smooth muscle cells (VSMC) by spectrofluorometry and direct videomicroscopic visualization of the renal microcirculation in isolated perfused hydronephrotic kidneys (IPHK). A fluorescein isothiocyanate (FITC)-labeled IAA-94 analogue showed specific binding to VSMC. IAA-94 (30 microM) neither affected basal cytosolic calcium concentration ([Ca2+]i) in VSMC nor peak response to ET, but it significantly curtailed sustained elevation of [Ca2+]i (half-time recovery was 147 +/- 23 vs. 248 +/- 33 s in control, P less than 0.05). IAA-94 blunted ET-induced membrane depolarization from 24.5 +/- 3.3 to 8.0 +/- 1.8 mV. In IPHK, ET constricted afferent arterioles (AA) by 29 +/- 2% (18.7 +/- 0.8 to 13.2 +/- 0.6 microns, P less than 0.001). Isradipine reversed this ET-induced vasoconstriction. Pretreatment with IAA-94 did not alter AA diameter, but markedly attenuated ET-induced AA constriction (reduction of AA diameters by only 9 +/- 2%, P less than 0.001). The subsequent addition of isradipine (0.1-1 microM) did not further dilate AA. Our data indicate that IAA-94 markedly attenuates AA vasoconstriction elicited by ET and suggest that ET-induced opening of chloride channels, membrane depolarization, and subsequent activation of voltage-dependent calcium channels contribute to the vasoconstrictor mechanisms of this peptide.
[An autopsy case of Marfan syndrome with bronchiectasis and multiple bullae].
We report an autopsy case (27-year-old male) with Marfan syndrome, who died of chronic respiratory failure due to bronchiectasis and multiple bullae in both lungs. He had suffered from expectoration of massive amounts of sputum since the age of 15 years. At this time, chest roentgenogram had revealed bronchiectatic changes in the bilateral lower lung fields. Seven years later at the age of 22 years, the formation multiple bullae in both lungs were added to the bronchiectatic changes on chest roentgenogram. Administration of erythromycin (400 mg/day) was started in February, 1987, and the massive sputum volume markedly decreased according to appearance of bullous formation. He was admitted to our department because of deterioration with chronic respiratory failure and right heart failure at 26 years in December, 1989. Although various therapy was performed, he died of chronic respiratory failure in February, 1990. Autopsy findings were as follows: (1) cyclindrical bronchiectatic changes in bilateral lower lobes and (2) extensive multiple bullae in the subpleural areas with bronchiectatic changes in the middle and bilateral lower lobes, with no bronchiectatic changes in the bilateral upper lobes. Several pulmonary disorders accompanying Marfan syndrome have been reported, especially in children. However, the present case demonstrated that fetal pulmonary involvement by Marfan syndrome may not present until adulthood, and affect both airways and lung parenchyma.
[Automated assay method for protein C anticoagulant activity].
We developed an automated assay method for protein C anticoagulant activity to prolong the APTT measured with automated coagulation apparatus. The automated assay method required following three reagents. One was 0.025 mol/l calcium chloride solution. The other two were a protein C deficient plasma and a phospholipid plus protein C activator both of which constituted a recomposed protein C assay kit (BMY). 0-50% activities of protein C and clotting times were regressed on normal linear curve, while 25-150% activities and clotting times were regressed on logarithmic curve. The coefficients of variation were 2.9-3.4% (intra-assay) and 3.6-3.9% (inter-assay). A correlation of protein C activities between measured by automated assay method and by ordinary manual method was good (r = 0.954). Our data suggest that this automated assay is a useful method for measuring the protein C anticoagulant activities utilizing a coagulation apparatus.
[A left subclavian arterial aneurysm ruptured into the left lung--a case report].
A 68-year-old man complained bloody sputum. Angiography revealed the left subclavian arterial aneurysm that was arising from the origin of the left subclavian artery. The aneurysm was resected with the adhesive lung tissue through a left posterolateral thoracotomy in the third intercostal space, and an 8 mm EPTFE graft was implanted between the aortic arch and the left subclavian artery. The aneurysm was filled with old thrombus and it was ruptured into the left lung. The pathologic study showed typical atherosclerotic changes. Postoperative course was uneventful, and his bloody sputum disappeared.
A new hereditary abnormal protein C (protein C Yonago) with a dysfunctional Gla-domain.
A familial abnormal protein C most probably with the dysfunctional Gla domain was found in a 60-year-old man with recurrent thrombosis. Namely, the anticoagulant activity as measured by the APTT method and the antigen level by an ELISA utilizing a calcium-dependent antibody were reduced to nearly half of normal, 43.5% and 2.1 micrograms/ml (normal range: 2.8-5.0 micrograms/ml), respectively. On the other hand, the amidolytic activity determined on a synthetic chromogenic substrate, S-2366, and the total antigen measured by an ELISA utilizing a polyclonal antibody were both in the normal range, 74.1% and 83% of normal, respectively. Crossed immunoelectrophoresis showed more anodal migration than the normal control in the presence of calcium ions, and adsorption of protein C to barium citrate was insufficient. These data altogether indicated that a half population of protein C in the patient's plasma was dysfunctional in the Gla domain or its related structures. Four other members of his immediate family were found to have the same abnormality of protein C, although they had been all asymptomatic. We thus conclude that the dysfunctional protein C is hereditary, and that the abnormalities noted in several tests are most likely due to a structural defect residing in the Gla or its related regions. We hereby designate this abnormal protein C as protein C Yonago.
Measurements of tissue factor-like activity in plasma of patients with DIC.
Tissue factor-like activity was measured in the plasma of 30 patients with disseminated intravascular coagulation(DIC) and 22 patients without DIC using a chromogenic substrate. Twenty-three of the 30 patients with DIC (77%) exhibited tissue factor-like activity levels above normal range (greater than 3.0 U/L), and in eleven of these patients, the levels were more than 10 U/L. Of the 22 patients without DIC, seven patients had elevated levels (3-10 U/L), and had a possibility to be developing DIC. So, we considered them to be in a pre-DIC state. No correlation was found between tissue factor-like activity and alpha 2 plasmin inhibitor-plasmin complex or FDP-D dimer. In a patient with acute monocytic leukemia, the elevated tissue factor-like activity (84.4 U/L) rapidly decreased after the initiation of chemotherapy, whereas in a patient with pancreatic cancer, the level remained elevated (67.4-79.2 U/L). These results suggested that the plasma tissue factor-like activity is differ from the other parameters reflecting the process of DIC and is a useful indicator of the presence of an initiating factor of blood coagulation in some selected patients with DIC or pre-DIC.
Quantitative analyses of the induction of chromosome aberrations and sister-chromatid exchanges in human lymphocytes exposed to gamma-rays and mitomycin-C in combination.
Most chemicals are S-dependent and are potent inducers of SCE, but do not produce chromosome-type aberrations in the first metaphases after exposure. Ionizing radiation, which is an S-independent agent, produces chromosome-type aberrations, especially dicentrics and rings, but inefficiently produces chromatid-type aberrations. A series of experiments has been performed to investigate whether cytogenetic damage induced by ionizing radiation (gamma-rays) might be assessed separately from that induced by the alkylating chemical, mitomycin C (MMC), when human lymphocytes were exposed to these 2 agents in combination. Whole-blood cultures of human lymphocytes in G0 phase were exposed to gamma-rays and MMC in combination or separately. Cytogenetic analyses were done for both chromosome aberrations (CA), analyzed in cultures incubated for 56 h without BrdUrd, and sister-chromatid exchanges (SCEs) in cultures incubated for 72 h with BrdUrd. The frequency of chromosome-type aberrations (dicentrics and rings) increased with increasing doses of gamma-rays from 0.5 to 4.0 Gy. The dose-response relationships were the same with or without concomitant treatment with MMC (10(-6) M). Although the SCE frequency increased with increasing doses of MMC, the increase was nearly the same as when cells were treated with both MMC and gamma-rays (2 Gy). There was no interaction between MMC and gamma-rays concerning these 2 endpoints.