IS THERE A SPECIFIC LINKAGE BETWEEN OBSTRUCTIVE SLEEP APNEA SYNDROME AND GASTROESOPHAGEAL REFLUX DISEASE?

Obstructive sleep apnea syndrome (OSAS) is a common condition characterized by repetitive sleep‐induced collapse of the upper airways. It is associated with increased risk for hypertension, ischemic heart disease, cerebral stroke, and traffic accidents. In contrast, gastroesophageal reflux disease (GERD) is a very common disorder defined as various symptoms or esophageal mucosal damage generated by the abnormal reflux of gastric contents into the esophagus. Patients with OSAS have been reported to have a high prevalence of gastroesophageal reflux (GER) symptoms. The increase of transdiaphragmatic pressure in parallel with the large negative intrathoracic pressure produced during apnea events may directly lead to GER. In addition, some studies have demonstrated improvement in GERD with the application of continuous positive airway pressure, most consistently effective treatment for OSAS. However, GER dose not occur with every apnea. Moreover, the common conditions observed in patients with OSAS, including obesity or alcohol ingestion, are also predisposing factors for GER. A more recent investigation in over 1000 subjects failed to show a causal link between both diseases. Thus, the potential relationship between OSAS and GERD remains controversial. Inconsistencies in definitions of both diseases or sampling biases may contribute to the confusing results.     

A case of drug eruption induced by hydroxyzine pamoate]

A 62-year-old woman with rheumatoid arthritis, Basedow's disease and arrhythmia has been treated with antirheumatic, antiarrhythmic drugs and so on. She developed pruritic diffuse erythema with papules on the trunk and extremities 2 days after taking hydroxyzine pamoate for asteatotic eczema. Laboratory data showed increased levels of eosinophils. Histopathological examination revealed a infiltrate of inflammatory cells in the upper dermis. Patch tests with hydroxyzine pamoate and hydroxyzine hydrochloride were positive. From these findings, we diagnosed this case as drug eruption due to hydroxyzine. Her eruption subsided after she discontinued hydroxyzine pamoate and other drugs which were started within 5 days before the onset of the eruption and was treated with systemic steroid, systemic antiallergic drug and topical steroid.     

Independent association of antibodies against human papillomavirus type 16 and E7 proteins with cervical cancer

The E4 open reading frame (ORF) of human papillomaviruses (HPVs) is transcribed in abundant mRNAs encoding an fusion gene during the productive infection, and the HPV 16 E7 ORF encodes an oncoprotein detectable in the cell lines derived from cervical carcinoma. We examined 421 human sera, which included 108 samples from the patients with cervical carcinoma, for the presence of IgG antibodies against the HPV 16 E4 and E7 proteins by enzyme-linked immunosorbent assay. Bacterially expressed fusion protein lac- and nonfusion protein E7 were purified and used as antigens. All of the 22 serum samples positive for anti-E7 antibody and the 11 out of 15 samples positive for anti- antibody were from the patients with cervical carcinoma, but only one sample was found to contain both anti- and anti-E7 antibodies. These findings show specific and independent association of these antibodies with cervical carcinoma.     

Fibrate for treatment of primary biliary cirrhosis

Recent studies of the effectiveness of ursodeoxycholic acid (UDCA) therapy in patients with primary biliary cirrhosis (PBC) reported that UDCA therapy did not necessarily stop the progression of liver fibrosis in all patients, even those with early stage PBC. Thus, there is a need for more effective treatments that could prevent asymptomatic PBC from progressing to the icteric stage. Bezafibrate is effective in approximately two-thirds of non-icteric patients who have not shown a complete response to UDCA. Serum bilirubin, aspartate aminotransferase and γ-guanosine 5'-triphosphate levelswere significantly lower in patients who responded to additional bezafibrate on univariate analysis. The putative mechanism by which bezafibrate acts in cholestasis is by increasing phospholipid output into bile, which forms micelles with the hydrophobic bile acid that reduces its toxicity.     

Characterization of adenosine deaminase (ADA)-negative B-lymphoblastoid cells cocultured with ADA-positive fibroblasts

Abstract: A cell line, BAD05, derived from B lymphocytes of an adenosine deaminase (ADA; EC 3,5,4,4)-deficient patient could not proliferate in a serum-free medium containing 100 μmol/l deoxyadenosine. When BAD05 was cultured with ADA-positive fibroblasts, the proliferation of BAD05 was improved. BAD05 cell density increased when the initially mixed ratio of fibroblasts/BAD05 was 1/10 or higher, but decreased when the ratio was 1/20 or lower. Deoxyadenosine concentrations in the medium and ATP and deoxyATP (dATP) levels in the BAD05 were measured after 4 hours of coculture at initial BAD05 cell densities of 1 × 10⁵and 1 × 10⁶cells/ml. Deoxyadenosine concentrations in the medium decreased as the density of fibroblasts increased. The dATP level decreased as the mixed ratio rose. The ratio of fibroblasts/BAD05 rather than the cell density of fibroblasts had a larger effect on the dATP levels in BAD05. Under our experimental conditions, ADA-negative cells proliferated well when the ratio of ADA-positive cells/ADA-negative cells was over 1/10.     

Gerstmann-Sträussler syndrome — A variant type: amyloid plaques and Alzheimer's neurofibrillary tangles in cerebral cortex

Summary This report presents a variant of Gerstmann-Sträussler syndrome (GSS). A 53-year-old female had developed slowly progressive dementia and atactic gait since the age of 45. No myoclonic jerks and periodic synchronous discharges were observed throughout the illness. The neuropathological study revealed that many amyloid plaques and widespread Alzheimer's neurofibrillary tangles (NFTs) appeared in the cerebral cortex. Characteristically, the plaques reacted with anti-prion protein and none of them reacted with anti- protein, and they were made of many components, including amyloid cores, macrophages laden with lipid granules and/or degenerated neurites. Neuropil threads were seen mainly in amyloid plaques. Moreover, plaques appeared which were confluent and laminar in arrangement in the fifth and sixth cortical layers and had a close relationship to the neuronal loss. There was no spongiform change in the cerebral cortex or cerebellum. The cerebellum was almost intact except for a few amyloid plaques. Ultrastructurally, some of the plaques simulated kuru plaques and others had many degenerated neurites possessing paired helical filaments and other accumulated organelles. GSS has been proposed to include cases with progressive ataxia, dementia and massive multifocal plaques in the brain with or without cerebral spongiform changes. The case presented here is a very peculiar case of GSS. Recently, similar cases have been reported in some large families, diagnosed as familial Alzheimer's disease. These cases may be a telencephalic form with numerous NFTs of GSS.     

The role of climbing fibers in the development of Purkinje cell dendrites

Destruction of the inferior olivary nucleus was performed in newborn kittens in order to study the role of climbing fibers in the postnatal development of the cerebellum. In the three kittens which survived for 40–45 days after the unilateral destruction at 2 days old, histological examination demonstrated the lack of dendritic arborization in many Purkinje cells in the cerebellar cortex contralateral to the lesion. The olivectomized kittens showed cerebellar symptoms which became conspicous when the kittens started to walk. The results reveal an important role of climbing fibers in the development of Purkinje cell dendrites.     

Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839)

Gefitinib (Iressa, ZD1839), an inhibitor of epidermal growth factor receptor-tyrosine kinase, has shown potent anti-tumor effects and improved symptoms and quality-of-life of a subset of patients with advanced non-small cell lung cancer (NSCLC). However, a large portion of the patients showed no effect to this agent. To establish a method to predict the response of NSCLC patients to gefitinib, we used a genome-wide cDNA microarray to analyze 33 biopsy samples of advanced NSCLC from patients who had been treated with an identical protocol of second to seventh line gefitinib monotherapy. We identified 51 genes whose expression differed significantly between seven responders and 10 non-responders to the drug. We selected the 12 genes that showed the most significant differences to establish a numerical scoring system (GRS, gefitinib response score), for predicting response to gefitinib treatment. The GRS system clearly separated the two groups without any overlap, and accurately predicted responses to the drug in 16 additional NSCLC cases. The system was further validated by the semi-quantitative RT-PCR, immunohistochemistry and ELISA for serological test. Moreover, we proved that the anti-apoptotic activity of amphiregulin, a protein that was significantly over-expressed in non-responders but undetectable in responders, leads to resistance of NSCLC cells to gefitinib in vitro. Our results suggested that sensitivity of a given NSCLC to gefitinib can be predicted according to expression levels of a defined set of genes that may biologically affect drug sensitivity and survival of lung cancer cells. Our scoring system might eventually lead to achievement of personalized therapy for NSCLC patients.     

Morphological investigations on axonal swellings and spheroids in various human diseases

Summary Axonal swellings and spheroids in various human diseases were studied by light and electron microscopy. 4 cases of infantile neuroaxonal dystrophy, 2 of degenerative diseases, 2 brain tumors and 3 of cerebrovascular disease were examined.Ultrastructurally most spheroids in infantile neuroaxonal dystrophy consisted of interconnected tubules, stacked membranotubular profiles, alternating layered membranes and accumulations of neurofilaments. Combinations of these four constituents were seen only in infantile neuroaxonal dystrophy. Torpedos (fusiform swelling of the axon of a Purkinje cell) consisted exclusively of neurofilaments. Spheroids in case 6 (mental retardation) and 7 (atypical teratoma) consisted of interwoven skeins of neurofilaments and grouped mitochondria. Spheroids in case 8 (demyelination) and 9 (cerebrovascular disease) consisted of packed complex bodies and mitochondria. Spheroids in cases 10 and 11 (cerebrovascular disease) consisted of degenerating organelles only. The morphological differences between cases 9, 10 and 11 probably depends on the severity and timing of the cerebral injury.Most spheroids show similar histological and histochemical properties, but ultrastructural study may give some clue to the origin of the bodies.     

Uncommon Type of Meningiomas with Conspicuous Plasmo-lymphocytic Infiltration: An Immunohistochemical and Histochemical Study

Two cases of meningioma revealing conspicuous plasmo lymphocytic tissue and hyalinized fibrous tissue components are reported. Histopathological examination of the plasmo lymphocytic infiltration was performed. Both lesions showed polyclonality of plasma cells as revealed by positive reactions for 1gG and paraimmunoglobulin χ- and λ light chains, and amyloid infiltration into the fibrous stroma and blood vessel walls. The histochemical and immunohistochemical characteristics of the lesion in relation to its etiology are briefly discussed. Acta Pathol. Jpn. 32: 190∼194, 1989.