Biomedical subjects
Publications and source records attributed to H Kanemitsu.
We experienced the case of left atrial myxoma originating from posterior leaflet mitral valve. Mitral valve repair was performed in that case, because of the presence mitral leaflet defect due to removal of the myxoma. Transesophageal echocardiography was a useful tool for perioperative evaluation of the mitral valve and precise localization of the origin of the myxoma.
Changes in gene expression including that of c-fos occur following cerebral ischemia. Proto-oncogenes c-myc and s-myc and oncosuppressor gene p53 are known to induce apoptosis in some types of cells, whereas proto-oncogene bcl-2 inhibits apoptosis. Possible induction of mRNAs for c-myc, N-myc, s-myc, c-fos, p53 and bcl-2 was examined following focal ischemia in the rat anterior cortex, hippocampus, thalamus and cerebellum by Northern blot analysis. Animals were decapitated 1, 2, 6, 12, and 24 hours following the left middle cerebral artery (MCA) occlusion. In sham-operated control rats, the mRNAs for c-myc, N-myc, c-fos and p53 were present in the anterior cortex, hippocampus, thalamus on both sides, and in the cerebellum, whereas those for s-myc and bcl-2 were not. The c-myc gene expression was rapidly and markedly induced by the MCA occlusion in the ipsilateral anterior cortex, hippocampus and thalamus in a time-dependent manner. In these regions, the c-fos gene expression was also induced as early as 1 hour after the MCA occlusion. The p-53 mRNA was induced in the ipsilateral hippocampus at 24 hours after MCA occlusion. In contrast, mRNAs for N-myc, s-myc and bcl-2 were not induced following MCA occlusion. These results indicate a possibility that high-level expression of the c-myc gene may be involved in the ischemic cellular events including apoptosis.
A 46-year old man, who had a history of right pneumonectomy for pulmonary tuberculosis 28 years ago, was referred to our hospital for surgical treatment of contralateral pneumothorax. The patient underwent multiple excisions of bullae and parietal pleurectomy through the median sternotomy in order to save pulmonary function. The postoperative course was satisfactory as he could maintain preoperative pulmonary function. He returned to his work soon. We consider that the median sternotomy would be the most useful approach to save pulmonary function of patients who plan to undergo surgical treatment of contralateral pneumothorax after pneumonectomy.
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Hippocampal neurons, when pretreated with sublethal ischaemia, acquired tolerance to future treatments of normally lethal ischaemia. The level of transcription of the stress protein hsp70 was studied by in situ hybridization in control, ischaemic and tolerance-induced-ischaemic hippocampal neurons. Mongolian gerbils were subjected to single forebrain ischaemia for 2 min (2-min ischaemia group: sublethal) or 5 min (5-min ischaemia group: lethal). Other animals, were exposed to sublethal ischaemia for 2 min and were subjected subsequently to ischaemia for 5 min, 2 days later. Animals were sacrificed at 6, 12, 24 and 48 h following ischaemia and in situ hybridization was performed with thin cross sections including the hippocampus. Hybridization of the hsp70 probe in the control group (no ischaemia) was barely visible in the brain. In the 2-min ischaemia group, intense hybridization was seen in the CA1 sector from 6 through 24 h of recirculation but hybridization almost disappeared at 48 h of recirculation. In the 5-min and the double ischaemic groups, the intense induction in the CA1 sector occurred during the period from 6 through 48 h of recirculation. Our present study by in situ hybridization reveals high levels of transcription of hsp70 message following 5-min of ischaemia, however no protein was detectable based on our previous experiments employing immunocytochemistry. In tolerance-induced hippocampal neurons, both hsp70 message and protein are present. These results suggest that tolerance-induced neurons are modified such that the hsp70 gene is both transcribed and translated. These changes most likely give rise to the tolerance observed in the double ischaemia group.
Gene transfection experiments demonstrated that over-expression of the s-myc gene under the control of a human metallothionein promoter induced apoptosis in cells such as rat and human glioma cells. In contrast to c-Myc-mediated apoptosis requiring withdrawal of serum growth factors, s-myc expression induced apoptosis in glioma cells in the presence of 10% fetal calf serum. Whereas, s-Myc-mediated apoptosis was suppressed in proportion to the increase of bcl-2 expression as seen in c-Myc mediated apoptosis. The s-myc gene was expressed in rat embryo cells being committed to differentiate to hypertrophic chondrocytes which undergo programmed cell death. CAT assay demonstrated that in the NH2-terminal region, the s-Myc protein contains a domain structure required for expression of transactivation activity that is approximately six times higher than that of c-Myc. Therefore, these findings strongly suggest that s-Myc may play an important role in transcription regulation of a set of genes whose expression induces programmed cell death in vitro and in vivo.
Bucillamine has been reported to have beneficial effects in rheumatoid arthritis. This report concerns a case of RA in which agranulocytosis developed while on a course of bucillamine. A 52-year-old female with RA developed a rapid fall in white blood cell count after 4 weeks of bucillamine treatment at daily dose of 50 mg. Agranulocytosis was diagnosed (WBC 1300/mm3, granulocytes 5%). The administration of bucillamine was halted and she was treated with only prophylactic antibiotic regime. The peripheral granulocyte count result rapidly reversed within 3 days after discontinuation of the bucilamine treatment. Anti-leukocyte antibody was detected by the leukocyte lysis phenomenon method during the period of agranulocytosis. And high intrinsic G-CSF activities were detected in the patient serum before the recovery period of agranulocytosis. Agranulocytosis is a rare side effect of bucillamine but it is potentially more harmful than other side effects. In treatment with bucillamine, therefore, the drug should be carefully administered and regular blood examinations carried out to prevent the occurrence of this side effect.
Following brief cerebral ischemia, tolerance to subsequent ischemia is induced in the hippocampal neurons. In this experiment, recovery of protein synthesis was investigated autoradiographically in gerbils with induced tolerance. The animals were subjected to single forebrain ischemia for 5 min (5-min ischemia group) or 2 min (2-min ischemia group). To observe the effect of tolerance acquisition, double forebrain ischemia (double ischemia group), 2-min ischemia followed by 5-min ischemia was induced 2 days later. At various recirculation periods (90 min, 6 h, 1 day, and 4 days following ischemia), animals received a single dose of L-[2,3-3H]valine. In the 5-min ischemia group, protein synthesis in the CA1 sector was severely suppressed during the period from 90 min to 1 day of recirculation and never returned to the normal level even at 4 day of recirculation. In the 2-min ischemia group, protein synthesis recovered gradually and returned to near normal at 4 days of recirculation. On the other hand, in the double ischemia group, recovery of protein synthesis in the CA1 sector was rapid. At 1 day of recirculation, protein synthesis returned to near normal. Protein synthesis in the CA2 sector was inhibited during the 4 days of recirculation in this group. The present study revealed an early recovery of protein synthesis in the hippocampal CA1 neurons in the gerbil with induced tolerance. We suggest that recovery of protein synthesis is essential for the survival of neurons exposed to transient ischemia.
Free radical reactions are supposed to cause ischaemic brain damage, and active oxygens can initiate these chains reaction. If active oxygens play important roles in ischaemic brain damage, the activity of superoxide dismutase, scavenger of superoxide anion, is supposed to decrease in ischaemic brain. The reduced form of ascorbic acid also scavenges superoxide anion. In rat middle cerebral artery focal ischaemia, we investigated the changes in superoxide dismutase activity and the concentration of reduced ascorbate up to 48 hours. Middle cerebral artery territory of each cerebral hemisphere was homogenized. The supernatant was divided into two aliquots; one was dialysed to remove ascorbate and the other was not. The enzyme activity of the dialysed specimen from the ischaemic hemisphere did not decrease within 4 h after the arterial occlusion. The activity of the dialysed specimen from the nonischaemic side remained unchanged during the examination. Reduced ascorbate levels in nondialysed samples showed similar changes to the superoxide dismutase activities in the dialysed samples. Our data suggest that ascorbic acid may exert the enzyme activity and that the enzyme activity remains at the normal level in the early phase of ischaemia despite the irreversible ischaemic changes that take place within 4 h after the onset of ischaemia.
We studied the activities of xanthine dehydrogenase and xanthine oxidase in rat forebrain after complete ischaemia. Complete ischaemia was induced by decapitation after transcardiac infusion with saline. The activities of xanthine dehydrogenase and xanthine oxidase immediately after ischaemia were 93.3 +/- 38.7 and 18.8 +/- 7.7 microU/mg protein, respectively, and at 24 h after ischaemia were 183.5 +/- 75.1 and 60.8 +/- 15.2 microU/mg protein, respectively. The ratios of xanthine dehydrogenase/xanthine oxidase immediately and 24 h after ischaemia were 5.04 +/- 1.03 and 3.04 +/- 0.99, respectively. These data indicate that xanthine dehydrogenase and xanthine oxidase activities were maintained even 24 h after complete ischaemia. Conversion of xanthine dehydrogenase to xanthine oxidase proceeds slowly during complete ischaemia.
It has been proposed that free radical reactions are involved in ischemic brain damage. Since irreversible pathological changes occurs very early phase of the focal ischemia and the ischemic brain edema reaches its peak at about 2 days of ischemia, the free radical reactions must take place before these changes. Superoxide dismutase is a famous enzyme that dismutase superoxide anion, which is believed to be one of the initiator of the free radical reactions. If superoxide anion plays a pivotal role in the genesis of pathological ischemic brain damage and edema, the activity of the enzyme may decrease in the early phase of ischemia. Ascorbic acid is also known to be a scavenger of superoxide anion, and brain tissue contains it in a high concentration. We investigated the changes in superoxide dismutase activity and concentration of reduced ascorbate in focal ischemia. Focal ischemia was produced in rats by permanent occlusion of the left middle cerebral artery. The animals were decapitated 30 minutes, 4, 24, and 48 hours after the operation. Middle cerebral artery territory of each cerebral hemisphere was homogenized and centrifuged with phosphate buffer. The supernatant was divided into two aliquots; one was dialyzed to remove ascorbate and the other was not. The SOD activity was measured by electron-spin-resonance (ESR) spin trapping method, and the ascorbic acid concentration was measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD). Protein concentration was measured by Lowry's method. The enzyme activity was expressed as unit/mg protein, and the ascorbic acid concentration was expressed as microgram/g tissue. The SOD activity decreased markedly by dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)
To explore the role of interleukins in development of arthritis, we induced collagen-induced arthritis in mice and examined interleukin activities in the inflamed joints. Arthritis developed in 90% of mice 4-5 weeks after primary immunization with type II collagen. Joint extracts from mice with collagen-induced arthritis contained high levels of interleukin 1 (IL-1)-like activity but not interleukin 2 (IL-2) or interleukin 4 (IL-4) activity. IL-1-like activities in the lesions were correlated with development of arthritis assessed by joint swelling and erythema. These results suggest that IL-1-like factor(s) may participate in the etiopathogenesis of collagen-induced arthritis in mice.
Natural bactericidal resistance to Mycobacterium bovis BCG is under the control of a single gene, designated Bcg. Lung granuloma formation in susceptible (Bcgs) and resistant (Bcgr) mice was studied in two sets of Bcg-congenic systems, namely, the BALB/c (Bcgs)-C.D2 (BALB/c.Bcgr) pair and the B10.A (Bcgs)-B10.Ar (Bcgr) pair, by using BCG as well as foreign body granuloma-inducing agents (dextran beads). Large granulomas of the lung induced by the intratracheal instillation of either BCG or dextran beads developed in Bcgs mice. In contrast, minimal inflammation was produced in Bcgr mice given BCG or dextran beads. Aqueous extracts prepared from pulmonary granuloma lesions induced by Bcgs mice by either BCG or dextran beads contained high levels of interleukin-1 (IL-1) activity but not interleukin-2 (IL-2) or interleukin-4 (IL-4) activity. Very low IL-1 activity was detected in extracts from Bcgr mice injected with BCG and dextran beads. The activity of IL-1 was correlated closely with the activity and size of the granulomatous inflammation in mice. These results suggest that pleiotropic effects of the Bcg gene are involved in the development of granulomas induced by either BCG or nonspecific foreign body agents (dextran beads) and that monokines participate in granuloma formation.
A 66-year-old man with kappa-light chain multiple myeloma had adult Fanconi syndrome. Renal tubular transport abnormalities consisted of renal tubular acidosis, renal glycosuria, aminoaciduria, phosphaturia and renal hypouricemia. After therapy for multiple myeloma, urinary Bence Jones protein became undetectable, and all these renal tubular abnormalities except urate wasting were corrected. Histological examination revealed electron-dense tubular and rod-like deposits in proximal tubular epithelium. This clinical observation suggests that the renal tubular transport defects were secondary to the myeloma process, possibly due to Bence Jones proteinuria.
Ureteral obstruction has been known to cause a renal acidification defect. To determine the underlying mechanisms of this defect, vacuolar-type H(+)-pump activity of the membrane vesicles taken from the rabbit renal outermedulla was measured in 24 hr obstructed and contralateral kidneys. H(+)-pump activity measured by acridine orange quenching method was resistant to oligomycin (10 micrograms/ml), vanadate (0.1 mM), and the absence of ambient K+, and it was highly sensitive to N-ethylmaleimide (0.5 mM) and dicyclohexylcarbodiimide (0.2 mM). H(+)-pump activity was 6.69 +/- 1.40 in the obstructed kidney, which was significantly lower than 10.32 +/- 1.88% AFU/mg.min in the contralateral kidney. In sham-operated rabbits, H(+)-pump activities were not different in both kidneys. Passive H+/OH- permeability measured by the rate of dissipation of the imposed pH gradient was not different in obstructed and contralateral kidneys. These results suggest that ureteral obstruction decreases vacuolar-type H(+)-pump activity of the kidney outermedulla, and this decrease may contribute to the distal acidification defect of obstructed uropathy.
Uric acid (UA) in the rat brain was measured by HPLC with an electrochemical detector following focal ischemia. At 24 h after the operation, the UA level in the ischemic center was 105.47 +/- 8.39 nmol/g tissue, whereas it was 8.36 +/- 1.86 in the sham-operated group. Allopurinol, xanthine oxidase inhibitor, almost completely inhibited this UA accumulation. These data demonstrate that the UA increase in the ischemic brain is due to the xanthine oxidase reaction.
The early morphological consequences of recirculation following middle cerebral artery (MCA) occlusion were studied in two rat models. The proximal MCA was occluded for 1 h by either a surgical clip or platelet thrombus; subsequently, 1 h of recirculation was facilitated. Following clip occlusion and recirculation, mild astrocytic swelling, especially around blood vessels, was detected in reperfused cortical and striatal areas. Neuronal changes included slight chromatin clumping and dilation of the rough endoplasmic reticulum. In contrast, severe structural abnormalities were detected following recanalization of the thrombosed MCA segment. Marked astrocytic swelling of cell bodies and perivascular processes with neuropil vacuolation were commonly seen. A heterogeneous pattern of neuronal alterations, including a high frequency of dense shrunken neurons surrounded by swollen astrocytic processes was documented in cortical and striatal regions. Severe neuronal changes were documented in brain regions exhibiting a well-perfused microcirculation. Vascular endothelial cells contained large numbers of pinocytotic vesicles associated with luminal and abluminal surfaces. Pronounced and rapid morphological changes evolve with reperfusion when thrombotic and ischemic events occur simultaneously. The basis for these rapid parenchymal changes following vascular thrombosis may involve acute alterations in cerebral microvascular permeability which exacerbate ischemic consequences.