[Amyloid angiopathy].
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Biomedical subjects
Publications and source records attributed to M Shoji.
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Seven thousand three hundred seventy-six sudden or violent manner of deaths were inspected or autopsied at Tokyo Metropolitan Medical Examiner's Office in 1989. Out of these victims, 693 (9.4%) victims were regarded as heavy drinkers on the basis of the drinking habits and the autopsy reports and 196 (2.7%) victims without past problem drinking were thought to be drunk at death from the family statements or the blood alcohol analysis. The total 889 (12.1%) alcohol-related cases (autopsy was performed on the 489 cases) were studied from epidemiological and etiological viewpoints. The average age of the alcohol-related victims (male: 811, female: 78) was 52 +/- 11 years. In middle-aged (45-54 years) men, 34% of the all sudden or violent deaths were alcohol-related. About half of the alcohol-related victims were living alone and jobless and they often died at home, particularly in the bed. In the alcohol-related victims, the blood alcohol concentration (BAC) analysis revealed that the average BAC of female was significantly higher than that of male. (2.12 +/- 1.73 mg/ml vs. 1.33 +/- 1.75, P < 0.01). This difference may be associated with sex difference in ethanol metabolism, body composition and drinking habits. Among the major causes of the alcohol-related deaths, alcoholic liver diseases accounted for 226 (25%), gastro-intestinal bleedings for 115 (13%), cardiovascular diseases for 105 (12%) and violent deaths (e.g., acute alcohol intoxication, falls, traffic accidents, suicide) for 329 (37%). By histopathological examination of the liver, about 30% of the alcoholic liver disease cases showed mainly fatty metamorphosis and 48% showed liver cirrhosis. Only 12% of the cirrhotics had either jaundice or ascites, suggesting hepatic failure. Alcoholic cardiomyopathy was suspected in only 11 cases. In conclusion, many people, particularly middle-aged men, lose their lives due to heavy drinking and there are many pathologically unexplainable sudden deaths of alcoholics.
BACKGROUND: After radical ablation of tumors, colon or jejunum is pulled up for reconstruction of the thoracic esophagus when stomach is unusable. However, esophagocolonic or esophagojejunal anastomotic leak is relatively frequent because of the potential for vascular insufficiency of conduit extended upward. METHODS: To overcome this disadvantage, 14 consecutive patients with esophageal or gastric carcinomas whose stomachs were unusable were subjected to thoracoesophageal reconstruction through upward extension of the jejunum with microvascular anastomosis. Jejunal vessels were used as graft vessels, and internal thoracic vessels were used as recipient vessels. If needed, arcade vessels were severed to ease extension. RESULTS: All extended jejunums survived, and there were no operative deaths. Two of four initial series of patients, whose arcade vessels were not severed despite undue tension at the anastomotic site, had esophagojejunal anastomotic leaks that healed spontaneously. CONCLUSIONS: Some clinical functional problems still exist, but we believe this a safe and useful method for reconstruction of the esophagus where stomach cannot be used.
The 4-kilodalton (39 to 43 amino acids) amyloid beta protein (beta AP), which is deposited as amyloid in the brains of patients with Alzheimer's diseases, is derived from a large protein, the amyloid beta protein precursor (beta APP). Human mononuclear leukemic (K562) cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta APP derivative essentially identical to the beta AP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length beta APP and M17 cells expressing only endogenous beta APP also released soluble 4-kilodalton beta AP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton beta AP that is essentially identical to the 4-kilodalton beta AP deposited as insoluble amyloid fibrils in Alzheimer's disease.
The ultrastructural localization of amyloid beta/A4 protein precursor (APP) in the brains of control and Alzheimer's disease patients was examined immunohistochemically using antisera against the N and C termini of APP. In both control and Alzheimer brains, immunoreaction for APP was seen in the cytoplasm of most neurons, on plasma membranes, outer membrane of mitochondria, granular substance and neurofilaments. Cell bodies and foot processes of astrocytes, containing glial filaments, were also labeled. In primitive and classic type senile plaques, APP immunoreaction products were localized in the astroglial processes that surrounded the amyloid mass of the senile plaques. Swollen degenerating neurites in the senile plaques were also labeled. Amyloid fibrils were negative with APP antisera.
Over the past 15 years, reconstruction following excision of malignant oral tumors was performed on 27 patients with segmental resection and five patients with hemiresection of the mandible. Following segmental resection, the mandible was reconstructed using an autogenous bone graft in eight patients in whom the surrounding soft tissues were fairly well preserved. Bony union was achieved in six of them. In the remaining two, the graft was removed because of postoperative infection, and one patient underwent secondary bone grafting. A pedicled myocutaneous flap and bone graft was used in seven patients who underwent extensive resection of the surrounding soft tissue. Bony union was achieved in three patients, and one developed pseudoarthrosis. The graft was removed in the remaining three because of postoperative infection. Reconstruction with only a metallic plate for stabilization of the mandible was carried out in six aged or sarcoma-affected patients. In two of them, the postoperative course was uneventful for 4 to 7 years. In the remaining four patients, plate removal was required because of exposure or tumor recurrence. In 5 of 11 patients in whom reconstruction was carried out with a combination of a pedicled myocutaneous flap and metallic plate, the postoperative course was uneventful for 2 to 8 years. Two of these five patients underwent secondary bone grafting. In four of the remaining six patients, the plate was removed because of exposure or improper adaptation to the stump. Two others died of disseminated intravascular coagulation syndrome within 1 month. A prosthesis was used more frequently by patients when reconstruction was performed using a pedicled osteomyocutaneous flap. The metallic reconstruction plate was helpful for restoring mandibular contour.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of "Kyushin" (KY-2), a drug containing toad venom, on a low-output-type heart failure model produced in rabbits by protease treatment on the left ventricular anterior wall, were examined. Heart rate, aortic blood flow (AoF), left ventricular systolic pressure (LVP) and maximal rate of rise of LVP (max dP/dt) in this model were maintained at lower levels than those in normal rabbits, while left ventricular end-diastolic pressure (LVEDP) and systemic vascular resistance (SVR) were maintained at higher levels, and the mean blood pressure (MBP) was at a normal level. KY-2 was administered intraduodenally to the animal. KY-2 improved heart failure state by increasing the AoF, LVP and max dP/dt, and by decreasing the LVEDP and SVR without a significant change in MBP. These results suggest that the beneficial effects of KY-2 on this heart failure model originate from their cardiotonic activity.
The cardiotonic and arrhythmogenic effects, and the excitatory effect on respiration of "Kyushin," a drug containing toad venom, were studied in comparison with those of digoxin. In anesthetized rabbits, the maximum rate of rise of left ventricular systolic pressure (max dP/dt) was measured as an index of cardiotonic effect, and the respiratory flow was measured as an index of respiratory function. Intraduodenal (i.d.) administration of 80 mg/kg "Kyushin" produced a cardiotonic effect and an excitatory effect on respiration, but i.d. administration of 16 mg/kg digoxin produced only a cardiotonic effect, and conversely inhibited respiration. In anesthetized open-chest guinea pigs, myocardial contractile force was measured as an index of cardiotonic effect and the arrhythmogenic effect was evaluated from the appearance of arrhythmic myocardial contraction. By i.d. administration of a 20% ethanol suspension or solution, "Kyushin" and digoxin showed a cardiotonic activity with doses higher than 40 mg/kg and 0.25 mg/kg, respectively. The arrhythmogenic doses of "Kyushin" and digoxin by i.d. administration were 2560 mg/kg and 2 mg/kg, respectively, suggesting that the safety margin of "Kyushin" is broader than that of digoxin.
To assess the interaction of endothelin (ET) with atrial natriuretic peptide (ANP) on cardiovascular and renal function, arginine vasopressin (AVP) release, and the renin-angiotensin-aldosterone system, either a low or high dose of ET (4 or 12 pmol.kg-1.min-1) was administered with ANP (26 pmol.kg-1.min-1) for 45 min after the initial infusion of ANP alone in anesthetized dogs. In the other groups, either ANP or saline alone was administered for 90 min. ANP alone decreased blood pressure (BP), cardiac output (CO), plasma aldosterone, and plasma renin activity (PRA), increased urinary Na and K excretion (UNaV and UKV, respectively) and urine flow (UF), but did not affect plasma AVP. The low dose of ET had no effect on these ANP-induced changes. However, the high dose of ET curtailed the responses to ANP, increased BP and PRA, and decreased UNaV, UKV, and UF associated with decreased renal plasma flow and glomerular filtration rate. High ET also further potentiated the decrease in CO and the increase in total peripheral resistance induced by ANP and increased plasma AVP. These results indicate that a dose of ET one-half that of ANP (on the molar ratio) may have completely counteracted vascular, hormonal, and renal responses to ANP.
To assess central effects of endothelin-1 (ET-1) on plasma arginine vasopressin (AVP), plasma atrial natriuretic peptide (ANP), blood pressure, heart rate, and renal solute excretion, ET-1 dissolved in the artificial cerebrospinal fluid was infused intracerebroventricularly (icv) at a dose of either 0.35 ng.kg-1.min-1 (0.14 pmol; LET) or 3.5 ng.kg-1.min-1 (1.4 pmol; HET) for 45 min in conscious rats. In the control study, ET-1 was omitted from the vehicle. Moreover, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-O-methyl-tyrosine]AVP (TMeAVP), a V1-blocker, and prazosin, an alpha 1-blocker, were peripherally administered. In the LET group, mean arterial blood pressure (MABP) increased without any changes in heart rate, plasma AVP and ANP, and renal solute excretion. In the HET group, MABP markedly increased with rises in plasma AVP and ANP, but urine flow, urinary osmolality, and urinary Na and K excretion decreased. TMeAVP attenuated the pressor response to ET-1, abolished rises in plasma ANP, and partially restored falls in urine flow. Prazosin after TMeAVP obviated the pressor response to ET-1. In the control, these parameters did not change, except for an increase in urinary solute excretion. These results showed that icv ET-1 stimulates the sympathetic nervous activity and plasma AVP, leading to increased blood pressure and renal vasoconstriction, with a reduction in renal water and electrolyte excretion.
Pharmacological effects of Gosha-jinki-gan-ryo extract (KJE) on experimental diabetes induced by cyproheptadine (CPH), aldose reductase activity, and experimental peripheral neuropathy were studied. The effects of KJE were compared with those of Hachimi-jio-gan-ryo extract (HJE). KJE at 417 mg/kg/day (5 times the daily dose in humans) and HJE at 367 mg/kg/day (5 times the daily dose in humans) significantly inhibited the decrease in glucose tolerance by CPH. KJE and HJE inhibited aldose reductase activity, when DL-glyceraldehyde was used as substrate, with IC50 values of 2.68 x 10(-5) g/ml and 4.45 x 10(-5) g/ml, respectively and when D-glucose was used as substrate, with IC50 values of 1.04 x 10(-4) g/ml and 1.55 x 10(-4) g/ml, respectively. KJE at 209 mg/kg/day (2.5 times the daily dose in humans) and HJE at 367 mg/kg/day significantly reduced peripheral neuropathy induced by crushing the sciatic nerve in rats. The potency of these effects of KJE was stronger than that of HJE, when a comparison was made on the basis of the daily dose.
The atrophic effects of a synthetic steroidal anti-androgen, TZP-4238, on the pituitary, prostate and adrenal gland of rats were investigated. Male Sprague-Dawley rats were divided into three experimental groups. Group 1 consisted of controls. Groups 2 and 3 received chlormadinone acetate (CMA) 50 mg/kg/day and TZP-4238 10 mg/kg/day p.o., respectively, for 3 weeks. CMA (Group 2) produced marked atrophy of the prostate. Furthermore, CMA caused marked atrophy of the adrenal gland. Histopathologically, the remarkable atrophy was observed in the adrenal cortical cells of zonae fasciculata and reticularis. The most striking ultrastructural alterations were noted in the mitochondria. In addition, intramitochondrial localization of glutathione-peroxidase (GSH-PO) which effectively reduces the lipid peroxides, was less than that in the controls. In the anterior pituitary gland, CMA induced a reduction in the size of ACTH cells. TZP-4238 (Group 3) produced marked atrophy of the prostate. However, TZP-4238 exerted no effect on the adrenal gland or anterior pituitary ACTH cells. In addition, the present histopathological study showed that TZP-4238 or CMA exerted no effect on the testes or anterior pituitary LH cells. Therefore, it is suggested that TZP-4238 causes atrophy of the prostate without any significant histopathological changes in the adrenal glands or anterior pituitary ACTH cells under the present experimental conditions. We further speculated that TZP-4238 had a more potent anti-prostatic effect than CMA and TZP-4238 had a less inhibitory influence than CMA on the pituitary-adrenal axis.
A 32-year-old man was diagnosed as having pseudo-Bartter syndrome due to surreptitious habitual vomiting and to maldigestion related to decayed teeth. His chief complaints were muscle pain and weakness. In this case, metabolic alkalosis, hypokalemia, hypochloremia, increased plasma renin activity and aldosterone levels were noticed with marked decreases in urinary chloride excretion. Creatinine clearance (GFR) and renal plasma flow (RPF) were also decreased. Blood pressure was normal, but the pressor response to angiotensin II was attenuated. Before treatment with 0.9% saline infusion, plasma vasopressin (AVP) was not suppressed sufficiently by lowering the plasma osmolality (Posm) with an oral water load (WL), but it normally responded to a rise in Posm due to hypertonic saline infusion. Moreover, plasma AVP was normally suppressed by WL after the replenishment of saline. Plasma atrial natriuretic peptide (ANP) was low before WL, but increased normally in response to WL. However, inconsistent with the normal response in this case, decreases in plasma AVP failed to dilute urinary osmolality and to increase urine flow, irrespective of the levels of plasma ANP. These results indicate that chronic inanition due to surreptitious vomiting causes impaired renal diluting ability through decreases in GFR and RPF, irrespective of the levels of plasma AVP and ANP.
To assess whether arginine vasopressin and atrial natriuretic hormone participate in impaired urinary dilution and excretion in glucocorticoid deficiency secondary to hypopituitarism, an acute oral water load of 20 ml.kg-1 BW was undertaken in the absence and presence of an oral hydrocortisone (60 mg) treatment in patients with ACTH deficiency (N = 7) and panhypopituitarism (N = 2). Plasma arginine vasopressin and atrial natriuretic hormone and renal water handling were simultaneously determined and compared with those in similarly water-loaded normal subjects. Plasma arginine vasopressin did not fall in response to decreased blood osmolality after an acute water load in the absence of hydrocortisone; plasma atrial natriuretic hormone did not change despite blood volume expansion; and impairment in urinary dilution and excretion remained. On the other hand, in the presence of hydrocortisone, plasma arginine vasopressin fell in response to a decrease in plasma osmolality and plasma atrial natriuretic hormone increased, thereby restoring urinary dilution and excretion. These results demonstrate that the impaired arginine vasopressin response to acute water loading play an essential role in deranged renal water and electrolyte handling in the state of glucocorticoid deficiency; the impaired release of atrial natriuretic hormone also may affect these disorders.
The purpose of this study is to develop a scale for measuring coping with job stressors. Stress process and coping function provide the theoretical framework. Coping is conceptualized as situation-specific behavior. We measure episodic coping, that is, the strategies that individuals actually use in coping with a particular situation. First, a preliminary scale, was prepared. It contained 39 coping behaviors with job stressor which were based on an open-ended pilot study. Next, factor analysis was conducted in order to identify the structure of the scale. Subjects of this study were 649 male employees and 91 female employees of a in manufacturing firm and research and development institute. By occupation they were comprised of 383 professionals, 99 technicians, 96 clerks, 104 miscellaneous workers and 58 of unknown occupation. Seven items in the preliminary scale were omitted because of their psychometrical properties. Finally, factor analysis showed three factors in the scale: positive action and cognition (11 items), avoidant action and cognition (10 items), and symptom management (11 items). The coping scale showed high conceptual validity and reliability.
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We immunocytochemically studied the expression of various epitopes of amyloid beta/A4 protein precursor (APP) after brain damage by kainic acid injection. After 3 h, APP695 rapidly accumulated in dystrophic neurites near the damaged site. After 3 days, APP with Kunitz-type protease inhibitor domain was expressed in reactive astrocytes in the lesion and ipsilateral hippocampus. APP rapidly accumulated in dystrophic neurites, and different types of APP were expressed in different cell types in the damaged brain.