[Autopsied case of Parkinson disease with neuroleptic malignant-like syndrome and rhabdomyolysis].
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Biomedical subjects
Publications and source records attributed to F Sasaki.
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Female mice were divided into androgenized (AF) and control (CF) groups. The AF mice were injected subcutaneously with testosterone propionate (Tp) and the CF mice with sesame oil at 5 days of age. Mammotropes (PRL cells) and somatotropes (GH cells) in the adenohypophyses of these mice when they became adults were studied with immunohistochemistry and morphometry by light microscopy correlated with routine electron microscopy. In CF mice, almost all of the PRL-immunoreactive cells (about 43% of all parenchymal cells) were type I (classical) PRL cells, and almost all of the GH-immunoreactive cells (about 30% of all parenchymal cells) were type I (classical) GH cells. Type II PRL cells accounted for about 0.4% of parenchymal cells, and type II GH cells were about 2.5% of all parenchymal cells. In AF mice, the percentages of PRL and GH cells were not significantly different from those of CF mice. Mammosomatotropes (Ms cells) in both groups were less than 1% of all parenchymal cells. Numbers of all parenchymal, PRL and GH cells, however, were increased significantly in AF mice when compared to those in CF, because the adenohypophysis was increased in volume in AF mice. Type I PRL cells were larger in AF than in CF. The ultrastructure suggested that type I PRL cells may show increased PRL synthesis and secretion in AF mice. Furthermore, AF mice, in which the hypothalamus is masculinized by the neonatal treatment with Tp, retained feminine characteristics in the population and size of PRL cells and GH cells in the adenohypophysis.
Adenohypophyses of porcine fetuses from 25 to 110 days of gestation were studied by immunohistochemical staining to ascertain the ontogeny of specific cell types and their spatial distribution in the pars distalis. No hormone-containing cells were found before 30 days of gestation. ACTH cells were observed first at 40 days, while GH and LH cells appeared first at 60 days. PRL cells were initially detected at 105 days. ACTH immunoreactive cells were also observed in the pars intermedia at 40 days. Blood capillaries were interposed between cell cords of the pars distalis after 40 days of gestation. ACTH cells were evenly distribution in all areas of the pars distalis except the rostral area (sex zone). GH cells were densely distributed in lateral wings of the pars distalis and immediately anterior to Rathke's lumen. PRL cells resembled GH cells in their distribution pattern, but PRL cells were fewer in number. LH cells were scattered in the sex zone of the pars distalis from 60 to 80 days of gestation. After 90 days, they became scattered throughout the pars distalis but were more numerous in the sex zone than in other areas. The inductive elements of adenohypophysial cells from Rathke's pouch epithelia are discussed. We hypothesize that cell cords of specific areas facing Rathke's lumen may differentiate into specific cell types of the pars distalis during fetal life.
Xenopus embryonic epidermis changes its cellular composition during development: the appearance of ciliated epidermal cells before hatching is a remarkable characteristic. In this study, the functional change of ciliated cells to mucus-secreting cells was examined with immunocytochemistry using anti-tubulin and anti-chondroitin 6-sulfate (C6S). Before hatching, most epidermal cells were labeled with anti-C6S in a granular fashion. Immunoelectron microscopy revealed that the anti-C6S-positive structure was the mucus granule. Ciliated epidermal cells lacked anti-C6S staining, but were strongly labeled with anti-tubulin. After hatching, most ciliated cells in the surface of the embryo disappeared. During their disappearance, some ciliated cells exhibited anti-C6S-positive granular labeling. This strongly suggests that the disappearance of ciliated cells is a functional conversion to mucus-secreting cells instead of shedding through cell death.
Hepatic regeneration following portacaval shunt was evaluated in the light of the changes of 3',5'-cyclic AMP (cAMP) levels in plasma and liver tissue, and also plasma cAMP levels after glucagon administration, using a 70% hepatectomy and portacaval shunt model in rats. Ratios of liver to body weight recovered to 60% of pre-operative ratios 2 weeks after the operation. Plasma cAMP level decreased slightly, but insignificantly, 1 day and 3 days after the operation, then recovered to the pre-operative level. Hepatic cAMP concentration increased for 2 weeks after the operation. Plasma cAMP levels induced after glucagon administration did not increase until 3 days after the operation and were only 50% of pre-operative levels 4 weeks after the operation. From these results, liver regeneration following the portacaval shunt was remarkably delayed, but continued until at least 2 weeks after the operation.
Two pediatric cases of inflammatory pseudotumor of liver were reported and compared with seven previously reported cases. Clinical presentation was variable but often consisted of fever and vague abdominal symptoms. These two cases were considered to be clinically malignant because angiographically one showed hypervascularity and the other showed the portal vein draining into the lesion to be occluded. There are four previous reports of similar cases complicated with occlusive phlebitis within and around the lesion. All but two of the reported cases underwent major hepatectomy or liver transplantation. However, because of the benign nature of the lesion, the treatment might be more conservative after adequate diagnostic procedures, including needle biopsy, are applied.
The extracellular matrix (ECM) is a complex of macromolecules that includes collagens, proteoglycans, and complex glycoproteins. In fibrotic liver tissue there is an increase in all of these matrix components, and they increase in serum in the patients with alcoholic hepatitis or liver cirrhosis. These ECM components have been used as a serum marker of hepatic fibrosis. Prolonged obstruction of bile flow results in morphologic and biochemical changes and the development of secondary biliary cirrhosis. In congenital biliary atresia (CBA) there is a close correlation between the degree of the hepatic fibrosis and bile flow after the operation. We estimated that, in CBA, ECM increased in serum, and it would reflect the degree of the hepatic fibrosis. To clarify this we examined the serum procollagen-III-peptide (P-III-P) and laminin in CBA patients. P-III-P was elevated in all preoperative patients but in two of the three postoperative patients whose jaundice disappeared P-III-P was in the normal range. In the all 3 patients whose jaundice continued, P-III-P was in normal range. Serum laminin was elevated in 12 preoperative patients with CBA, but there is no correlation between day of diagnosis and level of laminin. Mean concentration in CBA without jaundice after operation was 3.18 U/mL, 3.226 U/mL in CBA with jaundice and 3.3 U/mL in infantile hepatitis. There were no significant differences among three groups. With the elevation of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin, serum laminin level was also increased.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of immunotargeting chemotherapy for hepatoblastoma (HB) and hepatocellular carcinoma (HCC) following the application of adriamycin (ADM) or cis-platinum conjugated with anti-alpha-fetoprotein (AFP) antibody was evaluated experimentally and clinically. The conjugate was made from mouse monoclonal antihuman AFP antibody linked to ADM or CDDP, with a weight ratio of 2.5:1 via a dextran bridge. Experimentally, AFP-producing human HCC transplanted subsequently on nude mice was used. A mixture of the antibody and ADM or CDDP was prepared with the same ratio. Each drug was injected intraperitoneally, three times at the total dose of 14.4 mg/kg as ADM and one time at the dose of 8 mg/kg as CDDP. Tumor growth was inhibited significantly in the conjugate group compared with the other mixture group, the ADM or CDDP group, and the control group. Clinically, the conjugates were administered intraarterially in 4 cases (2 HBs and 2 HCCs) and intravenously in one case (1 HB). ADM and CDDP conjugated with anti-AFP antibody were used in 2 cases and 3 cases, respectively. Antitumor effects from the viewpoint of volume suppression rate showed partial response in 2 cases and no change in 3 cases. The immunotargeting chemotherapy using anti-AFP monoclonal antibodies may be a promising method for treatment of malignant epithelial liver cancer in children.
H-15 (HT-29-15) is an IgG1 mouse monoclonal antibody (mAb) to a cell surface antigen (molecular mass, 200,000 daltons) present on virtually all colorectal cancers and also in normal pancreatic ducts and bile ducts, but not in other normal tissues. The biological distribution and imaging characteristics of iodine-131 (131I)-labeled mAb H-15 were studied in 5 primary colorectal cancer patients and 9 patients with local recurrence of colorectal cancer. H-15 mAb labeled with 0.5-10 mCi of 131I was administered 7 to 8 days before surgery at 4 dose levels, ranging from 0.2 to 6 mg. Selective mAb H-15 localization to tumor tissues was demonstrated in 6 of 12 patients with antigen-positive tumors: in two patients, recurrent tumors were negative to H-15 mAb, although the primary tumors were positive. In six patients with positive radioimaging, tumor:normal tissue ratios ranged from 2.05 to 5.35 and tumor:serum ratios from 1.18 to 2.73. The clarity of images seems to correlate well with the latter ratios. Technetium-99 (99mTc)-albumin blood pool studies in selected cases showed that local recurrence of colorectal cancers was hypovascular, emphasizing the selective localization of mAb H-15 despite poor blood flow distribution in the tumors. The results altogether demonstrated that radioimmunodetection with 131I mAb H-15 is valuable for differentiating recurrent colorectal cancer from granuloma formation after surgery.
Different features in the fibroblasts and the macrophages, which are prominent cell types in the dermis of the dorsal tail fin of the larval axolotl, Ambystoma mexicanum, and the tadpole, Rana japonica, were examined by light and electron microscopy. At the non-metamorphic stages, the cytoplasm of the macrophage, loaded with numerous lysosomes, is generally located in the cell periphery. Outstanding was the presence of many ruffles or microvillous projections of different shapes and sizes in the plasma membrane. In contrast, the fibroblasts are spindle-shaped and possess less numerous microvillous projections compared with the macrophages, and extracellular spaces neighboring the fibroblasts are loaded with collagen fibers. The fibroblasts are located superficially and sometimes contact each other by the desmosomes. The macrophages are situated relatively deep in the dermis. At the metamorphic stages, both fibroblasts and macrophages contain many phagolysosomes in common, but the desmosomes still remain between the fibroblasts, and therefore the fibroblasts are distinguished from the macrophages. The macrophages are characterized by the their phagolysosomes which contain degenerating cells or cell debris of fibroblasts, myelinated nerve fibers and neutrophils. The macrophages also exhibit a higher endocytotic activity than the fibroblasts for the injected foreign particles (FITC-dextran or latex beads). On the other hand, the phagolysosomes (or autophagolysosomes) of the fibroblasts are characterized by intracellular collagen fibers. These different phagolysosomes between the macrophages and the fibroblasts mean that they may play different roles in the degeneration of the cellular or the extracellular components, respectively, of the tail fins during metamorphosis.
A 70-year-old woman was hospitalized for status asthmaticus. The level of CRP was high and chest roentgenogram showed infiltrative shadows in the left middle lung field. Artificial respiration and continuous infusion of methylprednisolone and aminophylline 750 mg/24 hr were performed. Eight hours after admission, seizures suddenly occurred. At this time, brain CT showed no abnormal findings. The seizures were thought to be induced by theophylline toxicity, since serum theophylline concentration was high at 69.9 micrograms/ml. Because theophylline clearance of the patient in a clinically stable condition was normal, it was speculated that theophylline clearance was reduced during status asthmaticus. It is thought that this rare case of theophylline toxicity occurred due to reduction of theophylline clearance during status asthmaticus associated with pneumonia.
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To understand the precise mechanism of bronchial hyperresponsiveness in patients with congestive heart failure, we studied the effect of mild pulmonary congestion on bronchial responsiveness to inhaled acetylcholine (ACh) in guinea pigs. We induced mild pulmonary congestion by inflation of a balloon placed in the left atrium, and maintained the left atrial pressure (Pla) at 10 mmHg for 30 minutes with continuous monitoring of lung resistance (RL) and dynamic compliance (Cdyn). Furthermore, we determined the provocative concentration of ACh producing 100% increase in RL (PC100-ACh), before and during balloon inflation. In animals with propranolol pretreatment, but not in animals without propranolol pretreatment, mild pulmonary congestion caused slight increase in RL (N.S.) and significant decrease in Cdyn (p less than 0.01) and PC 100-ACh (p less than 0.01). Cutting of bilateral vagal nerves partially inhibited the decrease of PC100-ACh, but pretreatment with either phenoxybenzamine, indomethacin, AA-861 or OKY-046 had not effect. These results suggest that blockade of beta-adrenergic receptors and the vagal reflex, but not of alpha-adrenergic receptors or arachidonates, contributes to bronchial hyperresponsiveness during acute pulmonary congestion.
Elastolytic enzymes and active oxygen species derived from leukocytes and alveolar macrophages during exposure to tobacco smoke, together with active oxygen species directly derived from tobacco smoke, are thought to play a crucial role in the pathogenesis of pulmonary emphysema by inactivating alpha 1 protease inhibitor (alpha 1 PI), a novel anti-elastase. We studied the inhibitory effect of probucol, an oral hypocholesterolemic agent, on tobacco smoke-induced decrease in plasma anti-elastase activity (EIA) and ferroxidase activity (FA) in conscious venous catheter instrumented rats. Rats exposed to the smoke of 5 cigarettes (nicotine 11 mg, tar 115 mg) in a plastic chamber showed a prompt increase in plasma COHb to 17.9 +/- 2.7%, and a prompt decrease in plasma EIA by -17.9% (p less than 0.05) and FA by -14.8% (p less than 0.01), which lasted for 6 hours after exposure. Rats administered probucol (1% probucol in food) for 3 days showed normal cholesterol plasma levels, and rats administered probucol for 4 weeks showed hypocholesterolemic plasma levels. EIA and FA were not depressed after smoking, and lipid peroxide product (TBA reactive substance) in lung tissue (p less than 0.05) and serum (p less than 0.1) showed a smaller increase in association with a smaller decrease in the ratio of lung tissue GSH/GSSG (p less than 0.01) compared with control rats. These results indicate that probucol, via its antioxidant action rather than its cholesterol lowering effect, has a protective effect on lung exposed to tobacco smoke in terms of protease-antiprotease balance and oxidant-antioxidant balance.
We studied the effects of inhaled and intravenous furosemide (40 mg) on bronchial responsiveness to acetylcholine (ACh) in patients with chronic congestive heart failure. The measurement of bronchial responsiveness was performed by inhaling doses of ACh and calculating the provocative concentration of ACh needed to cause a 20% fall in FEV1.0 (PC20-ACh). Intravenous furosemide (N = 11) had a marked diuretic effect (urine output 1014 ml (SEM 156) in 2 hours), but had no effect on resting pulmonary function and PC20-ACh. In contrast, inhaled furosemide (N = 10) had no effect on urine output and resting pulmonary function, but caused significant increase in PC20-ACh from 2.74 (GSEM 1.28) to 8.47 (GSEM 1.22) mg/ml (p less than 0.05). We conclude that inhaled furosemide, but not intravenous furosemide reduces bronchial hyperresponsiveness to ACh in patients with chronic congestive heart failure. The mechanism of this effect appears to be related to the ion transport system of airway epithelium.
We had a sixty-five year old male patient who suddenly complained of dyspnea and fever with pulmonary tuberculosis, severe respiratory failure, disseminated intravascular coagulation (DIC) and intractable bilateral pneumothoraces. From the first hospital day severe hypoxemia which did not respond to conventional oxygen therapy developed with a diffuse ill-defined reticulo-nodular shadow in the plain chest x-ray film. On the 2nd hospital day mechanical ventilation with 2cmH2O PEEP was introduced. Antituberculous agents as well as corticosteroids were started suspecting acute interstitial pneumonia with pulmonary tuberculosis and adult respiratory distress syndrome (ARDS). Medication was followed by the treatment of Gabexate mesilate and heparin against DIC on laboratory data. Though clinical findings and pulmonary infiltrate on chest x-ray film transiently improved, right pneumothorax occurred suddenly on the 6th day followed with left pneumothorax on the 36th day. Tube drainage of both pleural spaces and repeated instillation of thrombin-rich oxycel cotton via bronchofiberscope failed to stop air leakage. He ultimately expired on 49th hospital day. At postmortem lung had multiple bilateral bulla several of which ruptured to the pleural site and caseating necrotic area containing bacilli positively stained with Ziehl-Nielsen stain in the bilateral upper lobe. No typical caseating necrotic lesion, however, was found in the other lung tissue. Therefore, it seemed to show a chronic phase of diffuse alveolar damage (DAD).
The development of 31P-nuclear magnetic resonance (NMR) has enabled direct and non-invasive measurements of muscle metabolism. Serial measurements of the phosphocreatine/inorganic phosphate (PCr/Pi) ratio, which is closely related to the adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio and pH during and after forearm exercise were performed in 11 patients with chronic lung disease (CLD), nine patients with chronic heart failure (CHF) and eight control subjects. As compared with control subjects, the PCr/Pi ratio in the patients with CLD or CHF was lower during the recovery period and significantly lower at three and 4 min exercise. The pH values after exercise were lower in patients with CLD or CHF compared to control subjects. The PCr/Pi ratio at 4 min after exercise in the patients with CLD or CHF did not correlate with parameters of cardiac function or arterial and mixed venous oxygen tension. The arterial oxygen content and output in patients with CLD and CHF were significantly lower than that of control subjects. Nutritional parameters were not statistically different among the three groups. These observations suggest that metabolic abnormalities may be present in the skeletal muscles of patients with CLD and CHF that are not due to under-nutrition. These may result from reduced arterial oxygen output and, partially, from physical detraining.
Leukotoxin, a cytochrome P450-dependent metabolite of linoleate synthesized by neutrophils, caused dose dependent vasodilation (10(15)-5 x 10(-4) M) of isolated rat pulmonary arterial rings preconstricted with endothelin 1 (10(-8) M), although similar doses of linoleate had no effect. The relaxing effect of leukotoxin was largely ablated by mechanical denudation of the endothelium and by treatment with L-NMMA (1 mM) and methylene blue (5 x 10(-6) M), but not indomethacin (10(-5) M). Endothelium-independent relaxation of leukotoxin was not inhibited by pretreatment with nicardipine (10(-6) M) in both pulmonary arterial rings and aortic rings. In A7r5 cultured rat aortic smooth muscle cells, leukotoxin markedly inhibited Ca2+ uptake in the basal nonstimulated state, and in the stimulated state with endothelin 1. We conclude that leukotoxin causes vascular tone-dependent vasodilation via augmentation of EDRF production, and causes decrease of intracellular calcium concentration that is not related to the dihydropyridine-sensitive calcium channel, which may be a mechanism of the endothelium-independent relaxation caused by leukotoxin.