Retrograde cerebral perfusion against massive air embolism during cardiopulmonary bypass.
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Biomedical subjects
Publications and source records attributed to Y Iijima.
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A 63-year-old man with primary malignant lymphoma of the prostate is presented. The patient underwent total cystoprostatectomy and ileal conduit construction. The specimen revealed malignant lymphoma, diffuse small cleaved cell of the gland. Three months after the operation, local recurrence and enlarged lymph node development were demonstrated by computed tomography. The patient tolerated well a combination chemotherapy of VP-16, doxorubicin, cyclophosphamide and prednisolone for 5 cycles. Tumor recurrence and lymph node spread could never be recognized following this drug treatment. The patient has been asymptomatic after this chemotherapy for over 3 years.
We performed transurethral fulguration of the diverticular mucosa and incision of the diverticular neck in combination with transurethral prostatectomy or bladder neck resection to treat all aspects of diverticula in 9 patients. Eight cases with bladder outlet obstruction, involving 2 cases of large diverticula, have been successfully treated. A case with neurogenic bladder has failed. We found the transurethral procedure to be equally effective as open operation.
Severe type of ventricular arrhythmia was noticed after Cabrol's operation more frequently than usual reperfusion arrhythmia. Nine patients received Cabrol's operation and 2 of Bentall's were divided into 2 groups according to the occurrence of postsurgical ventricular arrhythmia (Lown's classification grade 0-3: 5 cases, grade 4 A-5: 6 cases), and then the factors contributed to the arrhythmia were analyzed. There were no significant differences between the 2 groups on the point of the characteristics of the cases with or without emergent surgery for, such as ruptured or dissecting thoracic aortic aneurysms or other complicated lesions, the degree of surgical damage, or preoperative cardiac function. The only significant difference between the groups was the angle overheading to the central point of left coronary orifice anastomosed with intermediate tube from the extensive line of the prosthetic flange obtained in the left anterior oblique views on the angiography. The mean value of the angle of the severe group (grade 4 A-5) was 41 +/- 6.8 degrees (mean +/- SD) and significantly acute than the angle of the other group (grade 0-3: 57 +/- 6.4 degrees). This fact suggested that the main reason of the ventricular arrhythmia was coronary ischemia caused by compression of the intermediate tube after formation of massive hematoma within the aneurysmal capsule wrapped over the composite graft.
We have studied metallothionein (MT) induction by three primary inducers; a heavy metal, a glucocorticoid and a cytokine, and by the combinations of these inducers in the cultured cells. MT-protein was synergistically induced by either a cytokine or a heavy metal with a glucocorticoid hormone and was additively induced by the combination of a cytokine and a heavy metal, but MT-mRNA levels were not completely correlated with MT-protein levels. These results suggest that posttranscriptional regulation may be involved in the synergistic induction of MT-protein. We propose a possible mechanism in which marked MT induction by stress in vivo is dependent on the combined effect of two or more inducers, because marked MT induction is not seen by an injection of a plausible dose of either a glucocorticoid hormone or a cytokine in vivo.
The heterodimeric glycoprotein hormones, human chorionic gonadotrophin (hCG), LH, TSH and FSH, consist of two non-covalently linked subunits, the alpha and beta subunits. The beta subunit is specific for each hormone and is responsible for the biological specificity, but the beta subunits of different hormones show some degree of structural homology. The CAGY (cysteine-alanine-glycine-tyrosine) region is one of the amino acid sequences that is homologous in different beta subunits and is highly conserved between species. In the present study, site-specific in-vitro mutagenesis was used to change three individual nucleotides in the centre of the CAGY region of the hCG-beta subunit, and the effects of these mutations on hCG production was determined by in-vitro transcription and then translation in Xenopus laevis oocytes. The results indicate that the CAGY region, particularly the glycine residue at position 36 in the beta subunit, is essential for the production of hCG. This finding is consistent with previous studies showing that this region is necessary for the biological activity of human TSH.
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The mechanism of metallothionein (MT) induction of the liver by endotoxin, which is mediated by a factor secreted by endotoxin-stimulated macrophages, was studied in vitro. MT induction of the liver cells by the endotoxin-stimulated macrophage conditioned medium was inhibited by a monoclonal antiepidermal growth factor (EGF) / transforming growth factor-alpha (TGF-alpha) receptor antibody, which acts as an antagonist of EGF and TGF-alpha. MT was induced by the substance, which was adsorbed by polyclonal antibody to TGF-alpha, but not by a monoclonal antibody to EGF, in the conditioned medium of endotoxin-stimulated macrophages. These results suggest that TGF-alpha secreted by macrophages is involved in MT induction by endotoxin.
We studied four eyes with retinal detachment accompanied by a break in the nonpigmented epithelium in the pars plicata of the ciliary body in three patients with atopic dermatitis. Each eye had either ectopia lentis or coloboma of the lens. In the region of the lens malformation, ciliary processes were hypoplastic. These rudimentary ciliary processes were observed only in the anterior half of the pars plicata. At their posterior end, the ciliary nonpigmented epithelium had been ruptured and a break by zonular traction was apparent. In the other region of the pars plicata, ciliary processes were normal and no break was detected. The break in the pars plicata was treated by diathermy application and segmental scleral buckling, without subretinal fluid drainage, and with the resulting reattachment of the retina. Hypoplasia of ciliary processes is basically responsible for the development of a break in the pars plicata.
This study assessed the incorporation of fluoride into remineralized enamel and the stability of the incorporated fluoride under various test conditions. Lesions were produced on bovine enamel slabs by a two-day immersion in 0.01 mol/L lactic acid buffer containing 3.0 mmol/L Ca, 1.8 mmol/L P, and 1% CMC adjusted to pH 4.0 at 37 degrees C. The remineralizaing solution contained the same amount of Ca, P, and CMC, plus 150 mmol/L NaCl and 3 ppm F, and was adjusted to pH 7.0 at 37 degrees C. All slabs were exposed to this unstirred solution, which was changed every two days during the ten-day remineralizing period. The remineralized slabs were divided into four groups. Group A (the control group) received no further treatment. The other three groups were exposed for 24 h to either the intra-oral environment (Group B), a 1.0 mol/L KOH solution (Group C), or a 0.01 mol/L lactic acid buffer (Group D). Fluoride incorporation assessed by abrasion biopsy in 10-microns layers showed about 10,000 ppm F maximum in Group A. Similar levels of fluoride concentration from the surface to approximately 30 microns thick were found in Groups A, B, and C. No appreciable fluoride was released from remineralized slabs from Groups B or C, and only a small fraction from Group D. Statistical analyses of the fluoride values showed no significant differences between the various test conditions in any of the layers sampled. No difference was evident in the Ca/P ratio between the ten-day remineralized enamel (Group A) and the treatment groups. The lack of appreciable fluoride loss from enamel with any of the above three conditions indicated a stable fixation of fluoride in the remineralized enamel lesions.
Epitope mapping of hTSH was carried out using 19 monoclonal antibodies prepared with hTSH or its beta-subunit as antigen. The affinity constants of the monoclonal antibodies ranged from 9.6 X 10(7) to 5.7 X 10(9) mol/l for hTSH. The binding activities of monoclonal antibodies were maintained or in some cases rather enhanced after removal of the sugar moiety of the subunits of hTSH, and completely diminished after reduction of intramolecular S-S bonds in the subunits of hTSH. Ten monoclonal antibodies recognized the epitopes on hTSH (alpha:beta subunit combined form) and on free alpha-subunit form. Eight other antibodies recognized the epitopes on free/or combined form of beta-subunit, all of which did not recognize any other human glycoprotein hormones. The monoclonal antibodies directed against the alpha-subunit could bind also other human glycoprotein hormones to a varying extent. On the basis of results from competitive binding studies, the antibodies directed against alpha-subunit and those against beta-subunit were each classified into five subgroups recognizing different antigenic determinants. The remaining one antibody recognized an epitope expressed only by hTSH and not by the free subunits. In addition, a positive cooperativity on the binding of hTSH was observed between monoclonal antibodies directed towards a particular epitope on the alpha-subunit and those towards a epitope on the beta-subunit. From these data, two-dimensional map of epitopes on hTSH was constructed. The epitopes on each subunit were found to form a cluster with complicated overlapping, suggesting a highly conformational structure.
The P100 peak latency of pattern visually evoked cortical potentials (P-VECP) was found to increase and amplitude decrease in the elderly depending on stimulus conditions. Using either of these as a criterion, changes of visual function with aging were quantitatively assessed both in humans and animals. Contrast threshold was found to increase at higher spatial frequency ranges and the luminance threshold increased more than 0.8 log unit. Also, the contrast threshold increased due to a smaller pupillary area and there was progressive decrease of the temporal frequency curves with age for lower frequency ranges of less than 10 rev/sec. In addition, a sensitivity decrease for the upper visual field was detected plus blue-yellow defects and a decrease in the amplitude of accommodation. In order to exclude the effect of senile changes of the crystalline lens, the luminance threshold, the accommodation power and color sense were investigated in pseudo-phakic eyes with a posterior chamber lens. No significant differences were found between phakic and pseudo-phakic eyes. Accordingly, it was suggested that reduced transparency and yellowish changes of the crystalline lens do not essentially contribute to the loss of function in the elderly found in the present study, but the neuronal pathway was responsible. As a clinical model of senescence, cases of juvenile parkinsonism were investigated, during L-dopa treatment and after ceasing it. The deficiency of the neural-transmitter of the higher visual pathway was indicated in the elderly, also. Animal experiments on neuronal dysfunction in rats and mice suggested no aging effects in ERGs, whereas VECP peak latency for higher temporal frequencies increased with age. The assumption that the elderly changes occur at the neuronal level was supported by a loss of optic nerve fibers in mice with age. The numbers of optic nerve fibers measured were 48,115, 50,875 in the 3-month-old and 6-month-old groups, respectively, and decreased to 43,175 in the 30-month-old group. Though our results indicated the senescence of visual function at the neuronal level, it was not as much as shown by other sensory organs. It was therefore presumed that there might be a certain feed-back system from the brain to the retina.
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Endotoxin induces a decrease in zinc concentration in the serum and an increase in zinc levels in the liver. We have studied whether metallothionein (MT), which is a heavy metal-binding protein, is associated with this phenomenon in vitro. When MT of liver cells is induced by a factor secreted by endotoxin-stimulated macrophages, the cells accumulate zinc from the medium. The temporal accumulation of zinc is correlated with the induction of MT, and the accumulated zinc binds to MT. These results suggest that zinc accumulation by liver cells is mediated by metallothionein produced in response to a macrophage factor, which is elicited by endotoxin.
We studied the effects of chronic treatment with a novel angiotensin converting enzyme inhibitor, alpha-[(2S,6R)-6-[(1S)-1-ethoxycarbonyl-3-phenylpropyl]amino-5-oxo-2- (2-thienyl)perhydro-1,4-thiazepin-4-yl]acetic acid.HCl (CS622), and a vasodilator, hydralazine, on plasma atrial natriuretic factor (ANF) levels and kidney ANF receptors in spontaneously hypertensive rats (SHR). Plasma ANF level was decreased and cardiac hypertrophy reduced in CS622 treated SHR, but not in hydralazine treated SHR, although blood pressure was lowered similarly in both SHR groups. The binding capacity of kidney ANF receptors increased and the affinity decreased in CS622 treated SHR compared to untreated SHR. These results suggest that decrease of plasma ANF results from decreased cardiac load but not from lowered blood pressure, and that changes in ANF receptors result from increased plasma ANF.
15-Hydroxyprostaglandin dehydrogenase was partially purified from hog gastric mucosa by about 1000-fold with a 13.5% yield. Its molecular weight was estimated to be 32,000 daltons by gel filtration. The enzyme was inhibited by some metabolites of plaunotol [(2E, 6Z, 10E)-7-hydroxymethyl-3,11,15-trimethyl-2,6,10,14-hexadecatetrae n-1- ol], a new anti-ulcer drug. The inhibition patterns for substrates, prostaglandin E1 and NAD+ were both uncompetitive with Ki values of 7.8 and 19.7 microM, respectively.
alpha-[(3S)-3-[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-2-oxo-6 or 7-phenylperhydroazepin-1-yl]acetic acids (monoester monoacids) and their dicarboxylic acids were synthesized, and their angiotensin-converting enzyme (ACE) inhibitory activities were evaluated. The dicarboxylic acids having phenyl substituents at the 6R, 6S, and 7S positions on the azepinone ring showed potent inhibition in vitro. The corresponding monoester monoacids, when administered orally, suppressed the pressor response to angiotensin I administered intravenously. The monoester monoacids having the phenyl substituent at the 6-position showed a longer duration of action than one having the substituent at the 7-position. The structure-activity relationship was studied on the basis of the conformational energy calculation.
An orally active renin inhibitor, ES 6864 (N-[(2R)-3-morpholinocarbonyl-2-(1-naphthylmethyl)propionyl]-(4- thiazolyl)-L-alanyl-cyclostatine-(2-morpholinoethyl)amide), was synthesized. ES 6864 was found to be a highly potent inhibitor of human renin with a Ki value of 7.3 x 10(-9) M. The compound competitively inhibited human renin. The inhibitor was also potent against monkey renin but was less effective against renins from pig, goat, dog, rabbit, and rat. ES 6864 did not inhibit cathepsin D, pepsin, trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at a concentration of 10(-5) M. ES 6864 was resistant to proteolytic actions of the enzymes in rat tissue homogenates (liver, kidney, pancreas, and small intestine). Oral administration of ES 6864 at 30 mg/kg to conscious, sodium-depleted marmosets produced a significant blood pressure reduction and almost complete inhibition of plasma renin activity, which persisted for 5 hours. Oral administration of ES 6864 also produced dose-related decreases of blood pressure in hog renin-infused rats, but the duration of action was much shorter than that in conscious marmosets. The parent compound in the blood following oral administration of ES 6864 to marmosets was confirmed directly by measuring the plasma concentration of ES 6864. These results enhance the possibility of developing renin inhibitors that can be used clinically.