[Clinical symptoms and physical findings in patients with COPD].
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Humans↗
Biomedical subjects
H Yagyu
Publications and source records attributed to H Yagyu.
Asialoglycoprotein receptor deficiency in mice lacking the major receptor subunit. Its obligate requirement for the stable expression of oligomeric receptor.
The asialoglycoprotein receptor is an abundant hetero-oligomeric endocytic receptor that is predominantly expressed on the sinusoidal surface of the hepatocytes. A number of physiological and pathophysiological functions have been ascribed to this hepatic lectin (HL), the removal of desialylated serum glycoproteins and apoptotic cells, clearance of lipoproteins, and the sites of entry for hepatotropic viruses. The assembly of two homologous subunits, HL-1 and HL-2, is required to form functional, high affinity receptors on the cell surface. However, the importance of the individual subunits for receptor transport to the cell surface is controversial. We have previously generated HL-2-deficient mice and showed that the expression of HL-1 was significantly reduced, and the functional activity as the asialoglycoprotein receptor was virtually eliminated. However, we failed to detect phenotypic abnormalities. To explore the significance of the major HL-1 subunit for receptor expression and function in vivo, we have disrupted the HL-1 gene in mice. Homozygous HL-1-deficient animals are superficially normal. HL-2 expression in the liver is virtually abrogated, indicating that HL-1 is strictly required for the stable expression of HL-2. Although these mice are almost unable to clear asialo-orosomucoid, a high affinity ligand for asialoglycoprotein receptor, they do not accumulate desialylated glycoproteins or lipoproteins in the plasma.
Animals↗
The LDL receptor is the major pathway for beta-VLDL uptake by mouse peritoneal macrophages.
In order to determine the contribution of the low density lipoprotein receptor (LDL-R) to the removal of apoB-containing native lipoproteins by macrophages, we compared the uptake of beta-VLDL in peritoneal macrophages (MPM) from wild type mice and mice lacking the LDL-R. The d<1.006 g/ml lipoproteins obtained from apoE deficient mice fed a high fat diet were poorly degraded by macrophages and caused only a slight formation of CE in macrophages from both types of mice. On the other hand, d<1.006 g/ml lipoproteins obtained from LDL-R deficient mice fed a high fat diet, beta-VLDL with apoE, were avidly taken up by and markedly stimulated CE formation in wild type macrophages, but not in macrophages lacking the LDL-R. The degradation of 125I-labeled-apoE-containing beta-VLDL by wild type MPM was poorly inhibited by unlabeled human LDL, and beta-VLDL without apoE had no effects. In conclusion, we propose that the in vitro uptake of native apoE-enriched lipoproteins by murine macrophages is primarily mediated by the LDL receptor and not by other apoE-recognizing receptor systems such as: the LDL receptor related protein, the VLDL receptor or the triglyceride-rich lipoprotein receptor.
Animals↗
Thiazolidinedione- and tumor necrosis factor alpha-induced downregulation of peroxisome proliferator-activated receptor gamma mRNA in differentiated 3T3-L1 adipocytes.
Thiazolidinediones (TZDs) are antidiabetic insulin-sensitizing agents that bind to peroxisome proliferator-activated receptor gamma (PPARgamma) and have potent adipogenic effects on 3T3-L1 preadipocytes. In fully differentiated 3T3-L1 adipocytes, TZDs markedly decreased PPARgamma mRNA levels without reducing the expression of genes that are positively regulated by PPARgamma, such as adipocyte lipid-binding protein 2 (aP2) or lipoprotein lipase-(LPL). PPARgamma mRNA levels were also downregulated by tumor necrosis factor alpha (TNFalpha), an antiadipogenic cytokine. We propose that the downregulation of PPARgamma is not the common denominator of the metabolic effects of TZDs and TNFalpha on mature adipocytes.
3T3 Cells↗
Infection of human lung fibroblasts with Epstein-Barr virus causes increased IL-1beta and bFGF production.
An association between Epstein-Barr virus (EBV) infection and fibroblast proliferation in the interstitial spaces of the lung has been suggested in idiopathic interstitial pneumonia. In this study we show that EBV can infect human lung fibroblasts in vitro. A primary-cultured human lung fibroblast cell line, designated CCD-32Lu, expressed EBV nuclear antigen 1 after coculture with lethally irradiated EBV producing cells. The infection further induced CCD-32Lu cells to produce the fibrogenic cytokines basic fibroblast growth factor (bFGF) and interleukin-1beta. These findings indicate that lung fibroblasts may be a target for EBV infection and suggest that EBV may play a role in increased production of these cytokines and induce fibroblast proliferation in idiopathic interstitial pneumonia.
Antibodies, Blocking↗
[Probucol].
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Angioplasty, Balloon, Coronary↗
Absence of ACAT-1 attenuates atherosclerosis but causes dry eye and cutaneous xanthomatosis in mice with congenital hyperlipidemia.
Acyl-CoA:cholesterol acyltransferase (ACAT) catalyzes esterification of cellular cholesterol. To investigate the role of ACAT-1 in atherosclerosis, we have generated ACAT-1 null (ACAT-1-/-) mice. ACAT activities were present in the liver and intestine but were completely absent in adrenal, testes, ovaries, and peritoneal macrophages in our ACAT-1-/- mice. The ACAT-1-/- mice had decreased openings of the eyes because of atrophy of the meibomian glands, a modified form of sebaceous glands normally expressing high ACAT activities. This phenotype is similar to dry eye syndrome in humans. To determine the role of ACAT-1 in atherogenesis, we crossed the ACAT-1-/- mice with mice lacking apolipoprotein (apo) E or the low density lipoprotein receptor (LDLR), hyperlipidemic models susceptible to atherosclerosis. High fat feeding resulted in extensive cutaneous xanthomatosis with loss of hair in both ACAT-1-/-:apo E-/- and ACAT-1-/-:LDLR-/- mice. Free cholesterol content was significantly increased in their skin. Aortic fatty streak lesion size as well as cholesteryl ester content were moderately reduced in both double mutant mice compared with their respective controls. These results indicate that the local inhibition of ACAT activity in tissue macrophages is protective against cholesteryl ester accumulation but causes cutaneous xanthomatosis in mice that lack apo E or LDLR.
Animals↗
[Extra-pulmonary tuberculosis].
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Humans↗
Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity.
Hormone-sensitive lipase (HSL) is known to mediate the hydrolysis not only of triacylglycerol stored in adipose tissue but also of cholesterol esters in the adrenals, ovaries, testes, and macrophages. To elucidate its precise role in the development of obesity and steroidogenesis, we generated HSL knockout mice by homologous recombination in embryonic stem cells. Mice homozygous for the mutant HSL allele (HSL-/-) were superficially normal except that the males were sterile because of oligospermia. HSL-/- mice did not have hypogonadism or adrenal insufficiency. Instead, the testes completely lacked neutral cholesterol ester hydrolase (NCEH) activities and contained increased amounts of cholesterol ester. Many epithelial cells in the seminiferous tubules were vacuolated. NCEH activities were completely absent from both brown adipose tissue (BAT) and white adipose tissue (WAT) in HSL-/- mice. Consistently, adipocytes were significantly enlarged in the BAT (5-fold) and, to a lesser extent in the WAT (2-fold), supporting the concept that the hydrolysis of triacylglycerol was, at least in part, impaired in HSL-/- mice. The BAT mass was increased by 1.65-fold, but the WAT mass remained unchanged. Discrepancy of the size differences between cell and tissue suggests the heterogeneity of adipocytes. Despite these morphological changes, HSL-/- mice were neither obese nor cold sensitive. Furthermore, WAT from HSL-/- mice retained 40% of triacylglycerol lipase activities compared with the wild-type WAT. In conclusion, HSL is required for spermatogenesis but is not the only enzyme that mediates the hydrolysis of triacylglycerol stored in adipocytes.
Adipocytes↗
Changes in squamous cell carcinoma-related antigen levels before and after hemodialysis in relation to the model of dialyzer employed.
OBJECTIVE: Although tumor marker levels in blood become elevated after hemodialysis as a result of the amount of fluid removed, serum squamous cell carcinoma-related antigen (SCC) levels have not been always reported to increase after hemodialysis. The purpose of this report is to determine whether there is a difference between the change of serum SCC levels before and after hemodialysis according to the model of dialyzer employed. PATIENTS AND METHODS: In ninety-four patients on hemodialysis (50 cases of diabetic nephropathy and 44 cases of glomerulonephritis), we examined serum SCC levels before and after hemodialysis. RESULTS: There was no overall difference between SCC levels before and after hemodialysis (3.2+/-1.5 ng/ml vs 3.3+/-1.7 ng/ml, p=0.2381). In patients treated with a cellulosic type membrane dialyzer (n=73), SCC levels after hemodialysis were higher than those before hemodialysis (3.7+/-1.7 ng/ml vs 3.5+/-1.5 ng/ml, p=0.0495). In patients treated with a synthetic type membrane (n=21), SCC levels after hemodialysis decreased when compared to those before hemodialysis (1.9+/-0.7 ng/ml vs 2.2+/-0.8 ng/ml, p=0.0018) and in all patients, the SCC levels after hemodialysis were lower than, or equal to, those before hemodialysis. CONCLUSION: The results suggest that the decline in serum SCC levels during hemodialysis treated with synthetic type membrane of dialyzers, concealed the increased SCC levels in hemoconcentration.
Antigens, Neoplasm↗
[Mixed connective tissue disease-associated interstitial pneumonia complicated by pneumomediastinum during prednisolone therapy].
A 59-year-old woman was admitted to our hospital with exertional dyspnea. Linear and reticular opacities in the middle and lower fields of both lungs were observed on chest roentgenograms and chest computed tomograms (CT). The presence of anti RNP-antibody and Raynaud's phenomenon, sclerosis of the fingers, and leukopenia yielded a diagnosis of mixed connective tissue disease associated with interstitial pneumonia. The symptoms and lung involvement were alleviated after the administration of prednisolone (40 mg/day). However, the patient experienced the sudden onset of dyspnea during pulmonary function tests. A chest X-ray film disclosed mediastinal air around the left pulmonary artery, and a chest CT scan demonstrated some blebs in the left lower lung field. After tapering the dosage of prednisolone in 5 mg increments per week, the pneumomediastinum disappeared without treatment. The clinical features and laboratory data findings suggested the patient's interstitial pneumonia was associated with systemic lupus erythematosus rather than with progressive systemic sclerosis or dermatomyositis. The pneumomediastinum may have been due to the rupture of blebs secondary to interstitial pneumonia during pulmonary function tests or as a result of steroid therapy.
Acute Disease↗
Embryonic lethality and defective neural tube closure in mice lacking squalene synthase.
Squalene synthase (SS) catalyzes the reductive head-to-head condensation of two molecules of farnesyl diphosphate to form squalene, the first specific intermediate in the cholesterol biosynthetic pathway. We used gene targeting to knock out the mouse SS gene. The mice heterozygous for the mutation (SS+/-) were apparently normal. SS+/- mice showed 60% reduction in the hepatic mRNA levels of SS compared with SS+/+ mice. Consistently, the SS enzymatic activities were reduced by 50% in the liver and testis. Nevertheless, the hepatic cholesterol synthesis was not different between SS+/- and SS+/+ mice, and plasma lipoprotein profiles were not different irrespective of the presence of the low density lipoprotein receptor, indicating that SS is not a rate-limiting enzyme in the cholesterol biosynthetic pathway. The mice homozygous for the disrupted SS gene (SS-/-) were embryonic lethal around midgestation. E9.5-10.5 SS-/- embryos exhibited severe growth retardation and defective neural tube closure. The lethal phenotype was not rescued by supplementing the dams either with dietary squalene or cholesterol. We speculate that cholesterol is required for the development, particularly of the nervous system, and that the chorioallantoic circulatory system is not mature enough to supply the rapidly growing embryos with maternal cholesterol at this developmental stage.
Animals↗
Ki-1 (CD30)-positive anaplastic large cell lymphoma, sarcomatoid variant accompanied by spontaneously regressing lymphadenopathy.
Although it has been reported that primary Ki-1 (CD30)-positive anaplastic large cell lymphoma (ALCL) of the skin may undergo spontaneous regression, it is rare for ALCL without cutaneous involvement to have spontaneously regressing lymphadenopathy. We report a case of sarcomatoid variant of ALCL accompanied by spontaneously regressing lymphadenopathy. The patient had gastric and pulmonary involvement of ALCL in addition to systemic lymphadenopathy, but with no cutaneous involvement. The lymphadenopathy spontaneously improved gradually during a period of one month without any treatment. At the same time, multiple small nodules in both lung fields decreased on chest computed tomography and multiple elevated gastric tumors with dimples were endoscopically recognized to have improved. He has since been treated with combination chemotherapy because of recurrence of the lymphadenopathy.
Adult↗
Cancer-associated retinopathy during treatment for small-cell lung carcinoma.
A 70-year-old woman with small-cell lung carcinoma (c-T4N2M0) was treated by six courses of combination chemotherapy (carboplatin and etoposide). After two weeks, she complained of a sense of darkness and night blindness. A Western blot analysis showed that the patient's serum bound with the recombinant 23-kDa retinal cancer-associated retinopathy (CAR) antigen at 1:1,000 dilution. Her visual acuity became so poor that she could only recognise a hand motion at 50 cm despite treatment with corticosteroids and combination chemotherapy. The patient was diagnosed as having a rare type of CAR because CAR is usually found before the diagnosis of primary cancer.
Adrenal Cortex Hormones↗
[Holter electrocardiogram monitoring as an indicator of cardiac involvement of sarcoidosis].
Sarcoidosis was diagnosed in a 55-year-old non-smoking woman because biopsy specimens of a subcutaneous tumor in her right cheek disclosed a noncaseating epithelioid granuloma. The patient had experienced exertional dyspnea and palpitation. Two months later, she was admitted because a Holter electrocardiogram (ECG) revealed bradycardia, 2:1 atrioventricular block (Mobitz II type) and ventricular premature beat (1.091 beats/day). ECG findings on admission changed from 2nd-degree to 3rd-degree atrioventricular block. A permanent pacemaker was implanted and the patient's symptoms subsided. Mediastinal uptake of Gallium-67 was observed and a defect of the cardiac septum was disclosed by Thalium-201 scintigram. Closer examination of the first Holter ECG revealed a Mobitz II type 2:1 atrioventricular block for about 3 minutes a day. Although the findings of the first Holter ECG initially disclosed a 2nd-degree atrioventricular block in our patient, a complete block developed within about 2 months after admission. In the follow-up of sarcoidosis patients, it therefore seems important to not only evaluate Holter ECG findings carefully, but repeat the examination at regular intervals.
Cardiac Pacing, Artificial↗
[Posterior mediastinal diffuse pleomorphic lymphoma].
A 26-year-old man presented with a 38 degrees C fever of undetermined origin in November 1977. His fever subsided in 1 month, but recurred concomitantly with dysphagia on December 10. For this reason, the patient visited our out patient clinic on December 15, and was hospitalized because a mass was found radiographically in the left lower lung field. A contrast-enhanced computed tomographic scan of the chest revealed an irregularly-shaped mass encircling the esophagus. Based on open-lung biopsy findings, the mass was diagnosed as non-Hodgkin's lymphoma, diffuse pleomorphic type. Neither swelling of the superficial lymph nodes nor hepatosplenomegaly was detected, and a bone-marrow aspiration specimen disclosed no atypical cells. Ga scintigraphy found accumulation only in this region, suggesting the posterior mediastinum as the origin of the lymphoma. Reports of non-Hodgkin's primary lymphoma in the posterior mediastinum are rare. Further, to our knowledge, there have been no reports at all on the diffuse pleomorphic type to date. This case was accordingly considered to be of highly informative value.
Adult↗
[A case of Morgagni's foramen hernia difficult to differentiate from lipoma].
A 61-year-old woman was admitted for chest discomfort. She had been admitted before, in March 1995, because of a lesion detected on chest roentgenograms. At that time, she was given a diagnosis of mediastinal lipoma based on the findings of chest computed tomography (CT) and magnetic resonance imaging (MRI), but was discharged without active intervention due to lack of subjective symptoms. During follow-up, the patient again reported chest discomfort beginning in March 1998. Because chest radiography disclosed. The tumor had enlarged, the patient was admitted to the hospital by our department. Chest MRI disclosed a mass with a signal intensity equal to that of subcutaneous fat in the pericardial space on both T1-weighted and T2-weighted images. Although sagittal images demonstrated continuity of the mass into intraperitoneal fat, a conclusive diagnosis of diaphragmatic hernia could not be made at that time. On April 30, 1998, a thoracotomy was performed on the basis of a preoperative diagnosis of mediastinal lipoma. During surgery, a hernial ring was observed slightly to the right and behind the sternum. The hernia consisted only of greater omentum, and was diagnosed as Morgagni's foramen hernia.
Diagnosis, Differential↗
[Motor neuron disease with respiratory insufficiency as primary manifestation].
A 66-year-old man with dyspnea on exertion suffered a cardiac arrest and was referred to our hospital after emergency room intubation. Chest X-ray films detected no abnormalities. Blood gas analysis showed hypoxemia with normal A-aDO 2, and pulmonary function tests revealed combined ventilatory impairment. Chest fluoroscopy revealed weakness of diaphragmatic motion. No other abnormalities were found on initial examination. It was difficult to wean the patient off mechanical ventilation and identify the cause of alveolar hypoventilation. On the 60th hospital day, a neurological examination and electromyography disclosed fasciculation and denervation of the left biceps and pectoralis major muscle. These findings supported the diagnosis of motor neuron disease (MND). Although respiratory insufficiency as an initial symptom of MND is unusual, physicians should be aware of the possibility of MND in cases of alveolar hypoventilation of unknown etiology.
Aged↗