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We measured the concentrations of soluble adhesion molecules in serum obtained from healthy volunteers and from patients with idiopathic pulmonary fibrosis (IPF) and the acute respiratory distress syndrome (ARDS). The concentrations of soluble intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and P-selectin were significantly higher in serum from the patients than in serum from the healthy volunteers. In patients with IPF, the concentration of soluble ICAM-1 in serum was inversely related to the vital capacity (expressed as a percent of the predicted value). The concentrations of L-selectin in serum from patients with ARDS were significantly lower than those in serum from healthy volunteers and from patients with IPF. These data suggest that serum-soluble adhesion molecules may be useful as markers of disease activity, severity, and prognosis in ARDS and IPF.

A 20-year-old woman was admitted to our hospital because of an abnormal shadow on a chest X-ray film. Laboratory tests done on admission showed high levels of tumor markers in serum. A computed-tomographic scan of the chest showed a multilocular cystic mass in the S10 of the right lung. Angiography revealed an abnormal artery that branched from the abdominal aorta, and therefore pulmonary sequestration was diagnosed. A right lower lobectomy was done. Analysis of fluid from the cyst revealed very high levels of CA19-9, CEA, and SLX. In an immunohistochemical study, epithelial cells of the cyst's walls were stained for CA19-9, CEA, and SLX. After the operation the levels of these tumor markers in serum were almost normal.

The purpose of this study is to clarify the relationship between 123I-MIBG lung uptake and silent myocardial ischemia (SMI), cardiac autonomic neuropathy (AN) or clinical characteristics. For the quantitative analysis, lung to upper mediastinum uptake ratio (L/M) and heart to upper mediastinum uptake ratio (H/M) were obtained from chest planar image. In addition, both lung washout ratio (%WR-L) and heart washout ratio (%WR-H) were calculated from early and delayed images. Each indices were compared in both diabetic and control groups. Mean values of H/M in diabetes with complication were significantly lower than those of control group. Particularly, AN(+)SMI(+) group showed lowest value. Similarly, mean values of %WR-H in diabetes with complication were significantly higher than those of control group and AN(+)SMI(+) group showed highest value. Although mean value of L/M in each diabetic group was significantly higher than that of control group, there was no statistical significance among each diabetes except AN(+)SMI(-) group on early image. Mean value of %WR-L in AN(+) or SMI(+) group was also significantly higher than that of control group, but there was no statistical significance among each diabetic group. The current study suggested that high pulmonary 123I-MIBG uptake in diabetes was independent of the complication of SMI or AN. Pulmonary endothelial dysfunction related with severity of diabetes mellitus was considered to be the most important factor.

A 47-year-old man was referred to our hospital because of hemoplysis. He had a history of chronic sinusitis and surgical treatment of a spinal arteriovenous malformation. A chest X-ray film and computed tomographic scan showed dextrocardia, diffuse bronchiectasis, and an aspergilloma in the right upper lung field. The source of the bleeding could not be detected by fiberoptic bronchoscopy. Transbronchial mocosal biopsy was done and examination of a specimen by transmission electron microscopy revealed the lack of inner and outer dynein arms. A chest X-ray film and computed tomographic scan of his nephew, who had a long history of productive cough showed dextrocardia and right lower-lobe bronchiectasis. These findings indicate that hemoptysis in patients with Kartagener's Syndrome can be caused not only by bronchiectasis but also by aspergilloma.

Guanylin, a 15-amino acid peptide, activates intestinal guanylate cyclase C receptor, thereby regulating intestinal fluid and electrolyte transport through the second messenger, cyclic GMP. To examine the role of the kidney in guanylin metabolism, we used a radioimmunoassay (RIA) to measure plasma concentrations of guanylin in 3 groups; normal individuals, patients who had renal disorders with normal or elevated serum creatinine levels (0.4Cre11.9 mg/dl), and patients who received hemodialysis (HD). The plasma concentration of immunoreactive guanylin in the normal individuals was 32.3 +/- 4.8 fmol/ml. The concentrations in 32 non-HD patients were correlated with their serum creatinine concentrations (r = 0.81, p0.0001). In 16 HD patients the plasma concentrations of immunoreactive guanylin before the start of HD were correlated with their dialysis duration (r = 0.63, p0.01). The plasma levels of immunoreactive guanylin in HD patients for whom EVAL membranes were used decreased one hour after the start of HD as compared with the prior levels. The plasma levels in HD patients for whom PC membranes were used showed no change. Ten kilodalton guanylin is the main component of guanylin molecules in the plasma and hemofiltrates of HD patients. These findings suggest that the kidney has a major role in the elimination and/or metabolism of guanylin. Uroguanylin, a member of the guanylin family that was recently isolated from human urine, also acts on the guanylate cyclase C receptor. Further studies of guanylin family peptides should provide a better understanding of the physiological roles of the kidney in the control of water and electrolyte balance.

We measured the levels of defensins, antimicrobial peptides, and cytotoxic peptides in azurophil granules of neutrophils in plasma, and in bronchoalveolar lavage fluid (BALF) from patients with the acute respiratory distress syndrome (ARDS). High levels of plasma defensins were observed in samples from patients with ARDS. Samples of BALF from patients with ARDS also had more neutrophils and higher concentrations of defensins than did samples from healthy volunteers and from patients with idiopathic pulmonary fibrosis or diffuse panbronchiolitis. In addition, the concentration of interleukin (IL)-8 in BALF was higher in patients with ARDS than in other subjects. A significant correlation was found between the concentration of defensins and that of IL-8 in BALF from patients with ARDS. These findings suggest that the lung injury in ARDS is caused by defensins released by neutrophils that accumulate in the lungs.

A high fever, coughing, stridor, and dyspnea developed in a 52-year-old woman on October 19, 1995. She went to a local clinic and was treated with oral penicillin and intravenous cefpirome. The symptoms worsened, and she was admitted to our hospital on October 26. Coarse crackles and wheezing were heard in both lung fields. The white blood cell count was 9000/mm3 and arterial blood gas analysis revealed a PaO2 of 49.8 Torr on room air. A chest roentgenogram obtained on admission showed a few small bibasilar nodular infiltrates, and a chest CT scan showed thickened bronchial walls along with small nodules having a centrilobular distribution. Of the cells in bronchoalveolar lavage fluid, 88% were neutrophils, but tests for bacteria and mycobacteria were negative. The cold-agglutinin titer was 1:512. The Mycoplasma pneumoniae antibody titer (IIIA) was 1:640 and viral serology tests were negative. Acute bronchiolitis due to M. pneumoniae was diagnosed and treatment with intravenous minocycline was started. The symptoms (coughing, fever, and stridor) resolved and the small nodules on chest CT scan disappeared, but hypoxemia remained. At the same time, an obstructive ventilatory defect (FEV1% 62.8%) and abnormal ventilation/perfusion lung scans were noted. Development into bronchiolitis obliterans was suspected, so administration of methyl prednisolone (1 g/day for 3 days) and prednisolone was started. The response to steroids was good. Pulmonary function improved and the arterial PaO2 at the time of discharge was 86 Torr (room air). Use of steroid therapy in the early phase of bronchiolitis obliterans seemed to be effective.

We report two cases of pneumococcal meningitis with paranasal sinusitis followed by cerebrovascular disease. Both cases were occupational divers, and had past histories of head trauma and paranasal sinusitis. Despite the combined therapy with antibiotics and dexamethasone, they developed cerebrovascular complications. Case 1 developed cerebral infarction and hemorrhage on day 13, and in case 2 cerebral infarction occurred on day 15. In both cases, serum levels of TNF-alpha and IL-6 were elevated in the early stage of the illness (12 pg/ml and 21.3 pg/ml in case 1, and 50 pg/ml and 7,570 pg/ml in case 2, respectively). In case 2, TNF-alpha, IL-1 beta and IL-6 levels in the cerebrospinal fluid were also elevated on day 4 (25 pg/ml, 320 pg/ml and 6,870 pg/ml, respectively). Thrombocytosis was observed in both cases before the onset of the cerebrovascular complications. These cytokines may play significant roles in thrombocytosis leading to cerebrovascular complications in pneumococcal meningitis. Although the use of steroids as adjunctive therapy for bacterial meningitis has been found to be beneficial, the dosage of dexamethasone administered in our cases may not be enough to suppress the synthesis and release of the cytokines. Therefore, administration of large doses of glucocorticoid should be recommended before the treatment with antibiotics.

Summary The aim of this study was to investigate the relationship between autonomic nerve dysfunction and myocardial uptake of l23I-meta-iodobenzyl guanidine (MIBG) in patients with diabetes mellitus. Twenty-two non-insulin-dependent diabetic patients, 9 with autonomic neuropathy [ANP( + )] and 13 without autonomic neuropathy [ANP( -)], and 8 controls were included in the study. Both planar and single photon emission tomographic (SPET) images were obtained 30 min (early) and 3 h (delayed) after the 123I-MIBG injection. The heart-to-mediastinal uptake ratio (H/M) and the washout ratio of 123I-MIBG (%WR) were calculated from planar images. The uptake ratio of the inferior wall to the anterior wall (I/A) and the %WR of both the inferior and anterior walls were calculated from the SPET images. On the early planar images, the mean H/M ratio in the ANP( + ) group was significantly lower than that of the control group. The mean %WR on the planar images in the ANP( - ) group was significantly higher than that of the controls. The SPET images demonstrated a reduction in MIBG uptake and significantly increased clearance in the inferior wall of the ANP( - ) patients. These findings extended to other areas of the heart in the ANP( + ) patients. In the quantitative analysis of the SPET images, the ANP( + ) group had significantly lower I/A values and significantly higher %WR values in the anterior wall. The ANP( + ) group showed significantly increased clearance of 123I-MIBG in the inferior wall. We conclude that 123I-MIBG myocardial scintigraphy is a useful diagnostic tool both in the early detection and evaluation of the progression of myocardial sympathetic nerve dysfunction in patients with diabetes mellitus. Both the I/A and %WR calculated from SPET images are useful parameters.

We present the two siblings with X-linked hydrocephalus (XLH) and discuss the clinical features and genetical analysis of them. Case 1. The proband, a male, was delivered by the emergency cesarean section because of enlarged head circumference (44cm). His head circumference at 24 years old was 92cm. Neurological examination revealed adducted thumbs, horizontal nystagmus, hyperreflexia and spasticity of legs. He had tonic convulsions. MRI revealed a very thin layer of cerebral cortex. Molecular analysis revealed a deletion of 5 bases in exon 8 of the cell adhesion molecule L1 (L1CAM) gene located at chromosome Xq28. Case 2. The younger maternal half brother of case 1 was also born by the cesarean section, with 48cm in head circumference. A ventriculoatrial shunt was placed at the first month old. Epileptic seizures were seen. At the age of 21 years he had a head circumference of 59cm. A physical examination showed bilateral adducted thumbs, upward deviation of eyes, hyperreflexia and spasticity of legs. CT showed marked generalized ventricular enlargement including the fourth ventricle. Molecular analysis confirmed the same mutations as that of case 1. A maternal uncle had a previous diagnosis of hydrocephalus, and a sister is identified as a heterozygous carrier from molecular genetical analysis. Our results indicate that HLX is caused by the mutations in the gene for neural L1CAM in our family.

X-linked hydrocephalus (HSAS) is the most common form of inherited hydrocephalus characterized by hydrocephalus due to stenosis of the aqueduct of Sylvius, mental retardation, clasped thumbs, and spastic paraparesis. MASA syndrome (mental retardation, aphasia, shuffling gait and adducted thumbs) and SPG1 (X-linked complicated spastic paraplegia) are also X-linked disorders with overlapping clinical signs. Linkage analysis studies implicated the neural cell adhesion molecule L1 (L1CAM) gene as a candidate gene for these X-linked disorders. This genetic study analyzes the L1CAM gene in a Japanese family with members suffering from HSAS, and describes a deletion of five nucleotides in exon 8. Screening by Bg1I digestion of polymerase chain reaction (PCR) products revealed that two siblings have the same mutation and a sister was identified as a heterozygous carrier. The 5 nucleotide deletion causes a shift of the reading frame and introduces a premature stop codon 72 nucleotides downstream, which might result in a truncated protein. The mutation identified herein is a novel L1CAM mutation, which triggers hydrocephalus. We report a unique L1CAM mutation that causes HSAS: the first report of such a mutation in a Japanese family.

Acrylamide (ACR) monomer produces neuropathy of the dying-back type and 4-methylcatechol (4-MC) is a potent stimulator of endogenous nerve growth factor synthesis. In the present study, we investigated the efficacy of 4-MC in promoting recovery from experimental ACR neuropathy in rats. Twenty-two Sprague-Dawley rats were made neuropathic by ACR injections. They showed hindlimb paralysis, increment of landing foot spread distance and a statistically significant reduction in motor nerve conduction velocity. After the ACR neuropathy had been established, 12 of the rats were administered 4-MC for 2 weeks, and the other 10 were injected with phosphate-buffered saline alone. 4-MC-administered ACR neuropathy rats showed improvement, i.e., a decrease in landing foot spread distance, increase in motor nerve conduction velocity and increase in nerve growth factor content in the sciatic nerves in comparison with the corresponding values for ACR neuropathy rats given phosphate-buffered saline alone. A decreased number of large myelinated fiber with a reciprocal increase in small myelinated fiber number also was seen in the ACR neuropathy rats; however, this change was ameliorated in part by the administration of 4-MC. Therefore, these findings suggest that 4-MC can accelerate the recovery process clinically, electrophysiologically, biochemically and neuropathologically.

A 32-year-old woman with a history of dilation and curettage for missed abortion at 31 years old had sudden hemoptysis during menstruation on May 25, 1993. She had catamenial hemoptysis again, and was admitted to our hospital on July 21, 1993. After admission, catamenial hemoptysis occurred, and a nodular shadow was noted in the right S4 area on chest roentgenogram and computed tomogram. A few days after menstruation, hemoptysis and the abnormal shadow on chest roentgenogram disappeared. Pulmonary endometriosis was diagnosed by clinical course, past history, and chest roentgenographic findings. During the next menstruation, hemoptysis and a nodular shadow in the right S4 area on chest roentgenogram recurred, so transbronchial lung biopsy and laparoscopy were done. TBLB specimens revealed macrophages with phagocytosed hemosiderin, and laparoscopy revealed pelvic endometriosis. She was treated with buserelin acetate. Catamenial hemoptysis and the nodular shadow on the chest roentgenogram disappeared after treatment.

Viral infection induces airway inflammation. It is possible that bronchial epithelium derived chemokine contributes to the migration and accumulation of inflammatory cells in the airway viral infection. We infected bronchial epithelial cells with influenza virus and analysed mRNA expression and production of RANTES. The expression of mRNA and the production of RANTES were detected in infected cells using RT-PCR method and ELISA.

A 35-year-old woman complained of acute progressive speech and gait disturbance after an upper respiratory tract infection. Neurological examination revealed cerebellar dysarthria, horizontal saccadic pursuit and slow saccadic eye movement, marked truncal ataxia, generalized hyperreflexia and mild sensory impairment of the bilateral lower limbs. She was diagnosed as having acute cerebellomyelitis. We considered her status as acute cerebellar ataxia. The neurological signs and symptoms rapidly improved with intravenous administration of high dose of glucocorticoid. Single photon emission computed tomography (SPECT) using 99mTc-HMPAO was performed on the 9th day and 50th day from the neurological onset. It showed an increased accumulation of 99mTc-HMPAO in the bilateral cerebellar hemispheres and vermis on the 9th day in spite of normal findings of Gd-DTPA enhanced MRI. Less accumulation was seen on the 50th day when her neurological signs almost improved. The accumulation may suggest the inflammatory process of the cerebellum. SPECT can be a useful method for evaluating the severity of cerebellitis.

Bronchial asthma is characterized as a chronic inflammation of the airway that causes an infiltration of lymphocytes and eosinophils. Cell to cell interaction or cell to tissue interaction is essential for infiltration of eosinophils to underlying tissues. These phenomena are closely related to the expression of intercellular adhesion molecule-1 (ICAM-1). Inhalation of steroids, such as beclomethasone dipropionate, is commonly used to cure airway inflammation. In this study, we investigated the effect of cytokines on ICAM-1 expression on human bronchial epithelial cell lines, NCI-H292. Moreover, the effect of dexamethasone on ICAM-1 expression stimulated by IL-1 beta, TNF-alpha and IFN-gamma was observed. Treatment with IL-1 beta, TNF-alpha and IFN-gamma dose-dependently increased ICAM-1 expression on NCI-H292 cells. Inhibitory effects were exerted by dexamethasone on ICAM-1 expression in cells stimulated by IL-1 beta and IFN-gamma in a dose-dependent manner, but not in cells stimulated by TNF-alpha. These results suggest that the inhibition of ICAM-1 expression could be related to the pharmacological action of steroid drugs.

Acrylamide monomer (ACR) causes central-peripheral distal axonopathy. We induced neuropathy in rats by means of ACR injection as an experimental model of the dying-back type of peripheral neuropathy to assess the potential efficacy of 4-methylcatechol (4-MC), a potent stimulator of endogenous nerve growth factor (NGF) synthesis, as a therapeutic agent for the axonal nerve lesion. ACR-induced neuropathy in rats resulted in a dying- back type of axonal degeneration, and a statistically significant reduction in motor nerve conduction velocity (MNCV), and density of large myelinated fibers. We administered 4-MC and ACR together to rats intraperitoneally and found improved clinical signs, and significantly more NGF content in sciatic nerves, faster MNCV, and greater myelinated fiber density than in rats given ACR alone. These findings suggest that 4-MC can prevent the progression of ACR-induced neuropathy and decreased NGF levels may be involved in the pathogenesis of ACR neuropathy.

Hypercalcemia and leukocytosis are often associated with primary lung cancer as a paraneoplastic syndrome. Recently, parathyroid hormone-related protein (PTHrP) and granulocyte colony stimulating factor (G-CSF) have been identified as major causative peptides for hypercalcemia and leukocytosis, respectively. We studied four men with advanced primary lung cancer (stages from IIIA to IV) who presented with hypercalcemia (corrected serum calcium levels: 10.5 mg/dl) and leukocytosis (WBC10,000 per mm3). The age of the patients ranged from 59 to 79 years old. The pathological subtypes were squamous cell carcinoma in three and adenocarcinoma in one. The mean serum calcium levels and leukocyte counts were 15.8 +/- 1.4 mg/dl (mean +/- SE) and 24,800 +/- 3,253 cells/mm3 (mean +/- SE), respectively. Abnormally high serum levels of PTHrP and G-CSF were found in three patients (mean +/- SE: 137 +/- 68 pg/ml; normal range in human serum,16 pg/ml), and in all four (mean +/- SE: 72 +/- 7.7 pg/ml; normal range in human serum,20 pg/ml), respectively. Immuno-histochemical examination of cancerous tissue obtained from these patients showed positive staining for both PTHrP and G-CSF within the cytoplasm of all the cancerous tissue. These results suggest that the association of hypercalcemia and leukocytosis in patients with advanced primary lung cancer is caused by production of both PTHrP and G-CSF by cancerous tissue.

A 70-year-old woman was admitted for productive cough and infiltrative shadows in the right lower lung field on chest X-ray film. Eosinophilia (17%) in blood, an abnormally high percentage of eosinophiles (7%) in bronchoalveolar lavage fluid and eosinophilic infiltration with proliferated goblet cells in transbronchial lung biopsy specimens led to the diagnosis of eosinophilic pneumonia. Laboratory data on admission also revealed a high level of CEA (17.1 ng/ml) in serum. After administration of prednisolone (30 mg/day), the symptoms ameliorated and the CEA levels were normalized. The proliferated goblet cells were immunohistochemically positive for CEA, which suggests that the high levels of CEA were caused by excessive CEA secretion from the goblet cells associated with eosinophilic pneumonia. These studies showed that serum CEA also may be a marker for disease activity in eosinophilic pneumonia.

123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed in 20 diabetic patients (NIDDM) and 8 control subjects to investigate the association between clinical autonomic nerve dysfunction and myocardial accumulation of MIBG. We used coefficient variance of R-R interval (CVR-R) as a index of the autonomic neuropathy and categorized diabetes into two groups (CVR-Ror = 2.0: non-autonomic neuropathy. CVR-R2.0: autonomic neuropathy). In planar imaging studies, heart to mediastinum MIBG uptake ratio (H/M) was calculated on both early and delayed images. The washout ratio of 123I-MIBG in the heart (%WR) was also obtained using myocardial tracer activity on the both images. Mean value of these indices in diabetic group did not reveal any significant difference with the value in the control group. On the SPECT images, low uptake was observed in the posterior-inferior wall with normal uptake of 201Tl in diabetic patients with non-autonomic neuropathy. These areas extended in patients with autonomic neuropathy. The mean value of count ratio of posterior-interior to anterior wall (posterior-inferior/anterior ratio: PI/A) in the diabetic autonomic neuropathy group was significantly higher than in the control group on the both early and delayed images. And the mean value of regional %WR in the posterior-inferior wall calculated by the both MIBG SPECT images was significantly higher in the non-autonomic neuropathy group than in the control group. In the diabetic patients, retention mechanism of 123I-MIBG was considered to be involved at an early stage without autonomic nerve dysfunction clinically. As autonomic neuropathy progressed severely, uptake mechanism was also supposed to be involved. Therefore, 123I-MIBG myocardial scintigraphy was useful for early detection of cardiac sympathetic nervous dysfunction in diabetic patients.

Synaptotagmin (p65), an integral membrane protein of synaptic vesicles, is thought to be involved in calcium-dependent exocytosis of synaptic vesicles. Here, we report the cloning and tissue distribution of a novel isoform of synaptotagmin, designated synaptotagmin III. The cDNA clones encoding synaptotagmin III have been isolated from a rat brain cDNA library. Rat synaptotagmin III is a protein of 588 amino acids having 40.5, 38.3, and 64.0% identity with rat synaptotagmin I, rat synaptotagmin II, and o-p65-C, a third synaptotagmin isoform of marine ray Discopyge ommata, respectively. The region of the two internal repeats homologous to the regulatory domain (C2 domain) of protein kinase C is highly conserved among synaptotagmin I, II, and III. RNA blotting studies reveal that synaptotagmin III mRNA is expressed in brain, various endocrine tissues, and hormone-secreting clonal cells. These results suggest that rat synaptotagmin III is a mammalian homolog of o-p65-C and is involved in Ca(2+)-dependent exocytosis of secretory vesicles in endocrine cells, as well as in neurons.

A 73-year-old woman was referred to our hospital because of left pleural effusion. Chyle was obtained by thoracocentesis. Because there was no organic lesion to cause chylothorax, idiopathic chylothorax was diagnosed. Her condition improved by chest-tube drainage and pleurodesis with intrapleural injection of OK-432. We report a rare case of idiopathic chylothorax and conclude that pleurodesis with intrapleural injection of OK432 is very useful for the treatment of idiopathic chylothorax.

Bronchial asthma is an inflammatory disease of the airways, and a simple method of evaluating inflammation, safer than BALF or bronchial mucosal biopsy, has long been sought after. The induction of sputa by the inhalation of an appropriate solution and the examination of the induced sputa may provide such a method. We compared the safety of two sputum induction methods, ultrasonically nebulized hypertonic saline inhalation and distilled water inhalation, and examined the usefulness of differential cell counts of the induced sputa. The safety of these methods was ascertained by determining lung functions (FEV1.0, PEFR) and urinary leukotriene E4 before and after inhalation of these solutions, and the usefulness of differential cell counts of induced sputa by examining the uniformity/reproducibility. Only after the inhalation of distilled water did the lung function reveal a statistically significant decrease when the data were compared with the control values for each of the two methods (p0.01), and when the data obtained with distilled water inhalation and hypertonic saline inhalation were compared (p0.05). The urinary leukotriene E4 levels obtained were not very different between the two methods; however, in two patients, urinary leukotriene E4 levels were increased markedly only after inhalation of distilled water. The uniformity of the sputum differential cell counts in the same specimen (evaluated by intraclass correlation coefficient) and inter-specimens (evaluated by Friedman test) was satisfactory for both methods, except for basophils. Hypertonic saline inhalation at 24-hour intervals gave a better reproducibility in differential cell counts of the induced sputa (evaluated by interclass correlation coefficient), when compared with distilled water inhalation. These results suggest that hypertonic saline inhalation is safer and more useful than distilled water inhalation for induction of sputum in a uniform and reproducible way, and that the induction of sputum by hypertonic saline inhalation will be clinically useful in asthmatic patients who cannot expectorate sputa spontaneously.

Ballism, which is seen relatively infrequently among movement disorders, is characterized by the abrupt onset of vigorous, rapidly executed, poorly patterned in voluntary movement of the limbs. Hemiballism is mostly associated with the lesion in the subthalamic nucleus. However, it occasionally occurs as a result of lesions outside the subthalamic nucleus. The natural history of hemiballism caused by vascular subthalamic lesion usually shows gradual disappearance within days or weeks. Death from exhaustion has however been reported in some patients within four to six weeks after the onset. Hemiballism caused by lesions outside the subthalamic nucleus tends to persist for a longer period. Intensive treatment is therefore required. Successful treatments of hemiballism with haloperidol or chlorpromazine are wellknown, but, in older patients, sulpiride can be the first choice of medications because of its lesser side effect.

A 36-year-old man who complained of bloody sputum showed a mass-like shadow in the right upper lung field on chest X-ray, which was diagnosed as adenocarcinoma by sputum cytology in August, 1990. Since his clinical stage was too advanced for curative operation, chemotherapy was started on October 1, 1990. On October 26, he brought up a polyp-like mass, and was found to have polypoid tumors on the bilateral tonsils and nasopharynx, which were biopsied and diagnosed as poorly-differentiated adenocarcinoma. On November 21, CT of the face showed soft tissue density tumors in the bilateral paranasal sinuses. According to the clinical course, all tumors were thought to be metastatic lesions. Since he had suffered from epistaxis and nasal obstruction due to the enlargement of metastatic tumors, nebulization chemotherapy and palliative resection were performed. In February 1991, he developed severe headache due to brain metastasis. Despite irradiation therapy, he died from cerebral intra-tumorous hemorrhage on February 22. We reported a rare incurable case of lung cancer with metastasis to the nasopharynx and paranasal sinuses.

A 31-year-old woman noticed progressive muscular weakness in the limbs and paresthesia in the fingers in February 1989. Paresthesia worsened and improved 4 times during 2 months. Intravenous edrophonium chloride failed to improve her muscular weakness. She had high antiacetylcholine receptor antibody titer in serum. We made a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) because of slow nerve conduction velocity (NCV), increased CSF protein, and the clinical course. Treatment with prednisolone improved muscular weakness and the slow NCV. Two years later she acutely had dyspnea, dysphagia, and muscular weakness after upper respiratory infection. Intravenous edrophonium chloride dramatically improved her symptoms. The diagnosis was made as myasthenia gravis (MG). After thymectomy her weakness was getting better without any medications. There may exist an autoimmune mechanism common, at least in part, to both CIDP and MG in our patient.

A 65-year-old female suffering from lumbago, headache, and hypertension had been treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive drugs. On June 13, 1990, 2 weeks after the commencement of loxoprofen administration, she developed cough and low grade fever. She was treated with antibiotics and NSAIDs without improvement. Laboratory data showed marked eosinophilia (2200/mm3), elevation of IgE (3090 IU/ml), and liver dysfunction. Her chest X-ray revealed no active lesion, but the percentage of eosinophils in BALF was elevated (38%). Because drug-induced eosinophilic pneumonia was suspected, all drugs were discontinued. Her symptoms improved and the abnormalities of laboratory data normalized. The lymphocyte stimulation test was weakly positive with three NSAIDs (loxoprofen, pranoprofen, and alminoprofen). The challenge test by loxoprofen reproduced eosinophilia and liver dysfunction, suggesting that she had loxoprofen-induced eosinophilic pneumonia. To our knowledge, this is the first reported case of loxoprofen-induced lung injury.

A 71-year-old male was found to have bilateral posteromedial masses on routine roentgenogram during admission for treatment of traffic accident related injuries. These masses were initially considered to be posterior mediastinal tumors, however, CT scan demonstrated a left diaphragmatic defect and the adipose nature of the bilateral masses (CT number: left -29, right -132). MRI also demonstrated a large amount of fat accumulation in the abdomen. CT scan and MRI are therefore very useful for the diagnosis of Bochdalek hernia in adults.

We isolated and identified IAPP[1-37] and IAPP[19-37] in normal rat pancreas by sequence analyses. Regional distribution and molecular forms of rat IAPP were studied by a highly sensitive and specific radioimmunoassay (RIA) for the peptide. IAPP[19-37], accounting for 57% of IAPP- immunoreactivity in rat pancreas, is a major molecular form of rat IAPP moiety. A large amount of IAPP (328.5 ± 25.0 pmol/g wet weight) was found in rat pancreas and the peptide was also detected in pyloric antrum of stomach, duodenum, jejunum, ileum, and colon at 0.1-0.8% of the level of pancreas. IAPP was immunohistochemically observed in B cells in the islets and the lower portion of the mucosa of gastrointestinal tract of the rat. IAPP was secreted from perfused rat pancreas in response to glucose. The distribution and secretion of IAPP suggest a possible endocrine or paracrine function in pancreas and gastrointestinal tract.

Islet amyloid polypeptide (IAPP) was isolated from a soluble peptide fraction of pancreata of non — diabetic patients and from normal human plasma using immunoaffinity chromatography, gel filtration and reverse — phase high performance liquid chromatography (RP- HPLC) coupled with radioimmunoassay (RIA). IAPP[1-37], IAPP[17-37], and other two IAPP—related peptides which were putative pro-IAPPs or different processing products of IAPP, were identified. Complete amino acid sequence of IAPP[1-37] was identical to that of IAPP identified in islet amyloid in the pancreas of patients with non- insulin- dependent diabetes mellitus (NIDDM) and in insulinoma amyloid. IAPP[1-37] is a major molecular form of IAPP in the pancreas, but it accounted for as little as 20-31% of immunoreactive IAPP in the plasma. IAPP was also found in the lower portion of the mucosa of the gastrointestinal tract, suggesting its endocrine or paracrine role in the gut. Plasma concentration of IAPP in normal individuals increased in response to glucose load. IAPP is a novel pancreatic hormone secreted from B cells under glucose stimulation. Amyloid deposition in the islets might be responsible for development of NIDDM.

We determined amino acid sequences of transthyretins of FAP patients from 10 countries. Serum transthyretin was isolated by using immunoaffinity chromatography and reverse — phase high — performance liquid chromatography (RP -HPLC). Six kinds of variant transthyretins with one amino acid substitution, Val30 → Met, Phe33 → Ile, Glu42 → Gly, Ser50 → Arg, Thr60 → Ala, and Ser77 → Tyr, were identified. Serum level of Met30 transthyretin in 29 Swedish, 4 Dutch, and 114 Japanese patients with type I FAP was 9.55 mg/dl, 11.31 mg/dl, and 9.86 mg/dl, respectively. A quantitative method for Met30 transthyretin deposited in tissues was developed by using radioimmunoassay (RIA) and extraction of the protein with formic acid. Met30 transthyretin occupied 0.8-1.8% of wet tissue weight in the heart, thyroid gland, and kidney, whereas, it comprised only 0.03% of wet tissue weight in the liver. A novel immunohistochemical technique using cyanogen bromide cleavage and an antiserum for subsequence[26-30] in Met30 transthyretin was useful for specific staining of amyloid Met30 transthyretin in tissue specimen.

The Mg2(+)-ATPase activity of cytoplasmic dynein isolated from bovine brain was examined in the absence of microtubules. Cytoplasmic dynein in the absence of microtubules showed Mg2(+)-ATPase activity with two distinct Km values, 272 microM and 11.8 microM. The initial burst of Pi liberation, which was due to occurrence of slow decomposition of reaction intermediate, was 0.67 mol per mol of cytoplasmic dynein. These results indicate that Mg2(+)-ATPase reaction of cytoplasmic dynein in the absence of microtubules is similar to that of flagellar and ciliary dyneins which have been shown not to hydrolyze ATP via a single pathway.

Contractile motility of the gallbladder and plasma cholecystokinin (CCK) responses to egg yolk administration were studied in 28 diabetic patients and 12 normal subjects. The patients were divided into three groups: group A (n = 10) had no diabetic neuropathy, group B (n = 8) had diabetic neuropathy with little autonomic neuropathy, and group C (n = 10) had advanced diabetic autonomic neuropathy. In groups A and B, contraction of the gallbladder after egg yolk administration was not significantly different from that of normal subjects. However, in group C, gallbladder contraction was impaired (p less than 0.01-0.05), compared with that in normal subjects. After the administration of egg yolk, plasma CCK levels increased from 12.4 +/- 4.5 to 25.3 +/- 12.0 pg/ml in normal subjects. In group A, plasma CCK levels increased from 17.9 +/- 8.5 to 39.3 +/- 14.2 pg/ml, and in group B, from 15.2 +/- 5.1 to 38.3 +/- 9.9 pg/ml. In group C, however, plasma CCK levels increased from 33.1 +/- 13.9 to 72.4 +/- 31.9 pg/ml, and fasting CCK levels and responses to egg yolk were significantly higher than those in normal subjects and in groups A and B (p less than 0.01-0.05). In conclusion, this study showed that in a group of diabetic patients with autonomic neuropathy, gallbladder contraction was impaired despite the exaggerated CCK response to egg yolk.

A case of hemiballism caused by infarction in the left striatum on MRI was reported. Hemiballism is generally associated with lesions in the subthalamic nucleus. However, hemiballism occasionally occurs as a result of lesions outside the subthalamic nucleus. Hemiballism is a benign condition with spontaneous recovery in most cases, but hemiballism caused by lesions outside the subthalamic nucleus is reported to tend to persist for a long term. In our case without involvement of the subthalamic nucleus, hemiballism so far continued for three months since the onset. Successful pharmacological treatments of ballism with haloperidol or phenothiazines were well known. In our case, the treatments of ballism with these drugs were unsuccessful due to drug-induced hepatic dysfunction. Instead of these drugs, ballism was improved by administration of 150 mg of sulpiride per day with no side effects. Sulpiride may be beneficial for persistent hemiballism caused by the extra subthalamic lesions.

To investigate effects of gangliosides on nerve growth factor (NGF) synthesis/secretion by Schwann cells, we obtained Schwann cells from dorsal sensory ganglia of one-day old Wistar rats and cultured them with various concentrations of a mixed ganglioside comprising GM1, GD1a, GD1b, and GT1b. NGF synthesis was evaluated by the measurement of NGF concentration in the conditioned medium using an enzyme immunoassay. In the continuous presence of 10(-3) M gangliosides, the NGF concentration in the medium showed a four fold increase on the 4th day, and it then decreased by the 8th day. The present results indicate that gangliosides promote the production/synthesis of NGF by Schwann cells.

A sensitive and specific radioimmunoassay for cholecystokinin (CCK) has been developed. Synthetic unsulfated carboxy-terminal fragment, CCK-8, was radioiodinated by the conventional Chloramine-T method. Antibodies were raised against sulfated CCK-8 covalently coupled to bovine thyroglobulin via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. By purification, highly immunoreactive 125I-labeled CCK-8 was obtained. The antiserum was highly avid, and plasma could be assayed directly. The detection limit of the assay was 5 pmol of sulfated CCK-8 per liter. The assay measured fragments CCK-8, CCK-33, and CCK-39 with equimolar potency. CCK-4, gastrin, and vasoactive intestinal polypeptide were not detected, even at higher concentrations. The concentration of CCK, as the sum of these CCK peptides, in plasma during fasting was low (10.5 +/- 2.1 pmol/L, mean +/- SEM) but still detectable in all normal subjects examined (range, 6.4-20.1 pmol/L). After ingestion of a test meal, CCK in plasma increased rapidly, peaking at 41.3 (SEM 5.7) pmol/L at 40 min and remaining high for 3 h after the meal. This supports the concept that CCK has important roles in digestion and absorption.

The effects of vasoactive intestinal polypeptide (VIP), dopamine, and somatostatin (SRIF) on GH secretion were examined in vitro in perifused pituitary adenoma tissues obtained at surgery from seven patients with acromegaly. The perifusion of VIP at 5 x 10(-8) M resulted in a significant increase in effluent GH levels in five of the seven adenomas. A dose-related GH response was observed from 5 x 10(-9) to 5 x 10(-7) M VIP in two adenomas examined. SRIF at 5 x 10(-8) to 10(-7) M suppressed not only baseline secretion of GH but also inhibited GH rises elicited by VIP in six of the seven adenomas. Dopamine at 5 x 10(-7) to 5 x 10(-6) M decreased the baseline secretion of GH in six of the seven adenomas. In four of the six adenomas responsive to dopamine, dopamine suppressed VIP-induced GH release when perifused simultaneously. In the remaining two dopamine-sensitive adenomas in which VIP alone failed to affect GH release, the inhibition by dopamine of GH release was blocked by VIP perifused concomitantly with dopamine. Synthetic TRH or theophylline perifused at the end of the experiment stimulated GH release in all of the adenomas, indicating the viability of tumor cells throughout the study. These results suggest that VIP stimulates GH release by its direct action on pituitary adenoma cells of acromegalic patients and that VIP, SRIF, and dopamine interact at the pituitary level in modulating GH secretion from these adenomas.