Seropositivity and epidemiology of human parechovirus types 1, 3, and 6 in Japan.

Human parechoviruses (HPeVs) mainly infect young children, causing mild gastrointestinal and respiratory diseases; however, HPeV type 3 (HPeV3) causes severe systemic diseases in young infants. To clarify the characteristics of HPeV infections from the aspects of seropositivity and epidemiology, we measured neutralizing antibody titres against HPeVs in individuals of in different age groups and isolated HPeVs from various clinical specimens in Niigata, Japan. The seropositivity to HPeV1, 3, and 6 was higher in older age group. HPeV1 and HPeV6 seropositivities were maintained in adults, whereas HPeV3 seropositivity was significantly lower in subjects aged >40 years (P < 0·001, P = 0·003). This result suggests that adults have increased susceptibility to HPeV3 as they lack neutralizing antibodies against HPeV3. Of the HPeV isolates, HPeV1 and HPeV6 frequently caused gastrointestinal symptoms. Moreover, gastroenteritis patients with HPeV1 and HPeV6 were mainly aged 6 months-1 year and ⩾2 years, respectively. In contrast, only HPeV3 was isolated from neonates and young infants with sepsis or sepsis-like syndrome, often with respiratory symptoms. These results suggest that clinical symptoms are clinically related to HPeV genotype and patients' age.

Large-scale DNA microarray analysis of atopic skin lesions shows overexpression of an epidermal differentiation gene cluster in the alternative pathway and lack of protective gene expression in the cornified envelope.

BACKGROUND: Atopic dermatitis (AD)-specific genes have not yet been clarified. Objectives To identify gene expression specific to active atopic skin lesions. METHODS: We analysed 23,000 genes in skin biopsy samples from 17 patients with AD and four normal controls using Affymetrix oligonucleotide arrays. RESULTS: Four of the 10 genes with the greatest differences in expression between patients and controls, S100A8 and S100A7 (upregulated), and loricrin and filaggrin (downregulated), were epidermal differentiation genes located on 1q21, a locus previously reported to have a genetic linkage with AD. CONCLUSIONS: Our results, showing downregulation of the cornified envelope genes and upregulation of the alternative keratinization pathway, are the first to suggest abnormal epidermal differentiation and defective defences as key abnormalities in AD.

Activation of alveolar macrophages in acid-injured lung in rats: different effects of pentoxifylline on tumor necrosis factor-alpha and nitric oxide production.

OBJECTIVE: To determine whether acid instillation augments tumor necrosis factor-alpha and nitric oxide production by alveolar macrophages in rats, and to study the effects of treatment with pentoxifylline before acid instillation on the production of these inflammatory mediators. DESIGN: Controlled laboratory investigation on tumor necrosis factor-alpha and nitric oxide production by alveolar macrophages of rats that had acid-induced lung injury. SETTING: University research laboratory. SUBJECT: Alveolar macrophages of rats. INTERVENTIONS: Alveolar macrophages were recovered by bronchoalveolar lavage at 4, 10, 16, 24, and 72 hrs after unilateral hydrochloric acid (pH, 1.0; volume, 0.1 mL) instillation into the lungs of rats. Alveolar macrophages then were cultured with or without lipopolysaccharide. One group of rats was pretreated with pentoxifylline before acid instillation. MEASUREMENTS AND MAIN RESULTS: Alveolar macrophages from both acid-instilled and contralateral lungs, which had recovered 24 hrs after acid instillation, produced significantly greater tumor necrosis factor-alpha and nitric oxide. Subsequent exposure to lipopolysaccharide, as a surrogate for bacterial infection, further promoted tumor necrosis factor-alpha and nitric oxide release. Alveolar macrophages from rats pretreated with pentoxifylline before acid instillation produced significantly less tumor necrosis factor-alpha and did not overproduce tumor necrosis factor-alpha when exposed to lipopolysaccharide. In contrast, pretreatment with pentoxifylline had no effect on nitric oxide production by alveolar macrophages. CONCLUSIONS: Acid instillation stimulates alveolar macrophages to produce tumor necrosis factor-alpha and nitric oxide. Pentoxifylline preserved innate production of tumor necrosis factor-alpha to lipopolysaccharide and did not inhibit the production of bactericidal nitric oxide. This may partly explain why pentoxifylline reduces acid aspiration-induced lung injury while maintaining the host's ability to combat bacterial infection after acid aspiration.

[Pretreatment of acid-induced lung injury with specific neutrophil elastase inhibitor ONO-5046 did not exasperate the subsequent bacterial lung infection by Pseudomonas aeruginosa].

Patients with acid lung injuries are at high risk for bacterial pulmonary infections which commonly occur several days after the acid aspiration. We reported that a specific neutrophil elastase inhibitor ONO-5046 inhibited the multi-organ injury caused by acid-instillation into the lung. In this study, we evaluated the effect of ONO-5046 on lung infection by Pseudomonas aeruginosa (PAO-1:Ps.) following acid-induced lung injury in rat lungs. Animals received 0.2 ml of hydrochloric acid (pH = 1) into the right lungs. Pretreated animals were administered ONO-5046 (30 mg.kg-1) i.v. 15 min. before acid instillation. Other groups received vehicle (saline). Twenty four hours later, they were instilled with 0.1 ml of Ps. 1 x 10(8) cfu into the left lungs. Four hours after bacterial challenge, the animals were deeply anesthetized and killed. Bronchoalveolar lavage was done on each lung separately to evaluate neutrophil elastase activity, neutrophil number and protein permeability of lung endothelium and epithelium. The numbers of Ps. in the lungs were measured. In the Ps.-instilled lung, the number of Ps. or the protein permeability was not increased with ONO-5046 pretreatment compared with those in the untreated group. Pretreatment inhibited the exasperation of the protein permeability indirectly caused by Ps. infection in the acid-instilled lung. It was indicated that ONO-5046 could inhibit the indirect lung injury caused by acid-instillation into the lung without aggravating the subsequent bacterial infection.

Transcranial bypass for spontaneous intracranial carotid artery dissection--a case report.

A case of spontaneous intracranial artery dissection (IAD) of the anterior circulation is reported. A 32-year-old man developed left hemiparesis with headache. Angiographies (AGs) showed progressive occlusion of the distal end of the right internal carotid artery. He underwent a superficial temporal artery-middle cerebral artery anastomosis 20 days after his initial symptoms. He improved gradually after operation. The prognosis and treatment of IAD are discussed. The authors conclude that cases with IADs of the anterior circulation should be followed up by cerebral AG or magnetic resonance angiography and that early bypass surgery should be considered to prevent massive cerebral infarction in some cases.

Migraine with aura-like headache associated with moyamoya disease.

A 49-year-old woman was admitted to our hospital because of severe headache. She had a 10-month history of migraine with aura-like headache that occurred every 7 to 10 days and was preceded by photopsia. Brain CT showed cerebral infarction of the left occipital lobe. Bilateral carotid angiograms showed vascular occlusions in the supraclinoid portion of the bilateral internal carotid arteries with telangiectatic vessels acting as collateral channels to the occluded distal carotid arteries, which were consistent with the diagnosis of moyamoya disease. Headache resolved gradually and has never developed again after the infarct of the left occipital lobe. Pathophysiological mechanisms of migraine-like headache were discussed. We conclude that borderline perfusion of occipital lobe cortex could be a trigger for the development of migraine with aura-like headache in susceptible patients. In the case of atypical attack of migraine detailed investigation should be done to detect underlying vascular diseases such as moyamoya disease.

[Meningioma associated with acute subdural hematoma: a case report].

We present a case of meningioma associated with acute subdural hematoma. This 67-year-old male had a sudden onset of severe headache when he was on the train. He had a CT scan which revealed an acute subdural hematoma at the left parietal convex. Cerebral angiography disclosed a small focus (3 x 4 cm) of vascular stain under the left parietal bone supplied by the left middle meningeal artery. He was diagnosed as having a meningioma with surrounding acute subdural hematoma. The removal of this tumor was carried out without delay. It was fragile and the bleeding point was not detected. Pathological diagnosis was meningothelial meningioma. The literature showed meningioma associated with acute subdural hematoma is rare, but when it is discovered incidentally, surgical resection might be indicated.

A novel 4-methylumbelliferyl-beta-D-xyloside derivative, sulfate-O-3-xylosylbeta1-(4-methylumbelliferone), isolated from culture medium of human skin fibroblasts, and its role in methylumbelliferone-initiated glycosaminoglycan biosynthesis.

Human skin fibroblasts were incubated in the presence of 4-methylumbelliferyl-beta-D-xyloside (Xyl-MU). The culture medium was recovered and Xyl-MU derivatives which were initiated by the Xyl-MU acting as a primer were purified. As a result, a novel Xyl-MU derivative was isolated, in addition to previously reported Xyl-MU derivatives such as glycosaminoglycan-MU, Gal-Gal-Xyl-MU, Gal-Xyl-MU, SA-Gal-Xyl-MU, Xyl-Xyl-MU, GlcA-Xyl-MU, and sulfate-GlcA-Xyl-MU. This Xyl-MU derivative was subjected to carbohydrate composition analysis, enzyme digestion, ion-spray mass spectrometric analysis, and Smith degradation. The results indicated that it was sulfate- O -3-Xyl-MU. When Xyl-MU was incubated with [35S]PAPS using a homogenate prepared from the same cultured skin fibroblasts, [35S]sulfate- O -3-Xyl-MU was produced. Moreover, when Xyl-MU was incubated with UDP-[3H]Gal, [3H]galactose was transferred to Xyl-MU, but when sulfate- O -3-Xyl-MU was incubated with UDP-[3H]Gal, [3H]galactose was not transferred. These results indicate that chain elongation from Xyl-MU is inhibited by sulfation of Xyl-MU, and that Xyl-MU sulfation is involved in the control of Xyl-MU-initiated glycosaminoglycan biosynthesis.

Long-term administration of "sho-saiko-to" increases cytochrome P-450 mRNA level in mouse liver.

Simplified differential display of mRNA was applied to isolate and identify genes transcriptionally regulated in mouse liver by sho-saiko-to administration. A cDNA fragment up-regulated by sho-saiko-to was isolated and characterized. cDNA sequencing and subsequent database analysis revealed that the fragment showed significant sequence similarity with mouse testosterone 16-alpha-hydroxylase (cytochrome P-450[16alpha]) cDNA. The increased level of mRNA expression of cytochrome P-450(16alpha) in association with sho-saiko-to administration suggests the molecular mechanism of the chemopreventive effect of sho-saiko-to. This result indicates the usefulness of the mRNA differential display technique to investigate the molecular mechanism of Kampo medicine.

[Valproate induced parkinsonism].

Among side effects due to sodium valproate (VPA) administration, parkinsonism is very rare. We report here three cases of VPA induced parkinsonism. Case 1 (75 year-old-woman) developed parkinsonism (rigidity, akinesia, postural instability) 41 month after the VPA administration (800 mg/day). Parkinsonism resolved within 6 months of discontinuing VPA. Case 2 (70 year-old-man) developed parkinsonism (rigidity, akinesia, postural instability, frozen gait) 15 months after the VPA administration (800 mg/day). Parkinsonism resolved within 6 months of discontinuing VPA. Case 3 (74 year-old-woman) developed parkinsonian gait 7 months after VPA administration (800 mg/ day). Parkinsonian gait resolved within a month of reducing VPA. Pathophysiologic mechanisms of this rare toxic reaction remain unknown. VPA induced parkinsonism is not so rare and has been under-reported and under-recognized. When we are confronted with the patients who develop parkinsonism after VPA administration, the possibility of VPA induced parkinsonism should be considered in the differential diagnosis. Old age, long duration of treatment, and VPA dose maintaining serum therapeutic levels might be predisposing factors for this syndrome.

Characterization of beta-D-xyloside-initiated glycosaminoglycan synthesized by human skin fibroblasts in the presence of tunicamycin.

Human skin fibroblasts were incubated with a fluorogenic xyloside, 4-methylumbelliferyl-beta-D-xyloside (Xyl-MU), in the presence or absence of tunicamycin. The xyloside-initiated glycosaminoglycans (GAG-MUs) were isolated from the culture medium, and their structures characterized. When the cells were incubated with Xyl-MU in the presence of 0.2 microg ml(-1) tunicamycin, the synthesis of GAG-MU was increased about three fold, compared with the control value in the absence of tunicamycin (cells exposed to Xyl-MU alone). The structures of GAG-MUs synthesized in the presence or absence of tunicamycin were compared by HPLC analysis using gel-filtration and ion-exchange columns, enzymatic digestion, and unsaturated disaccharide composition analysis. The data indicated that cells incubated with tunicamycin produced more undersulfated and shorter GAG-MUs than cells without tynicamycin. These results suggest that tunicamycin inhibits the elongation and sulfation of glycosaminoglycan (GAG) chains and that, as a result, GAG-MUs with shorter chains and undersulfated residues, but possessing a large number of GAG chains, are synthesized in the presence of tunicamycin.

Internal carotid-posterior communicating artery aneurysm manifesting as an unusual ocular motor paresis after minor head trauma--case report.

A 75-year-old female fell down in the road and hit her head. Two days later her right eye abduction was slightly limited on right lateral gaze. Cerebral angiography revealed an ipsilateral internal carotid-posterior communicating artery aneurysm. Craniotomy found the aneurysm had compressed the oculomotor nerve and was successfully clipped. The ocular motor paresis completely resolved after the operation. Therefore, the ocular motor paresis was possibly due to the aneurysmal compression to the oculomotor nerve. The oculomotor nerve stretched over the aneurysm was probably vulnerable to sudden mechanical stress, and aberrant innervation of the oculomotor nerve might be responsible for this unusual ocular motor paresis. Minor head trauma might precipitate ocular motor paresis in patients harboring an otherwise occult mass lesion at the skull base.

Effect of monensin on the synthesis of beta-D-xyloside-initiated glycosaminoglycan and its linkage region oligosaccharides in human skin fibroblasts.

Human skin fibroblasts were cultured with a fluorogenic xyloside, 4-methylumbelliferyl-beta-D-xyloside (Xyl-MU) as an initiator, and the effects of monensin, which destroys the normal structure of the Golgi complex, on the synthesis of Xyl-MU-initiated glycosaminoglycan (GAG-MU) and its linkage region oligosaccharides were investigated. When the cells were incubated with Xyl-MU in the presence of monensin, the synthesis of GAG-MU was inhibited. In addition, the synthesis of Galbeta1-3Galbeta1-4Xylbeta1-MU as an intermediate of GAG-MU was inhibited, whereas the synthesis of Galbeta1-4Xylbeta1-MU, which is formed prior to Galbeta1-3Galbeta1-4Xylbeta1-MU, was not. These results indicate that inhibition of GAG-MU synthesis by monensin occurs at the point where the second galactose is joined to Galbeta1-4Xylbeta1-MU.

Mutism developing after bilateral thalamo-capsular lesions by neuro-Behçet disease.

We described a 44-year old right-handed man showing mutism, left hemiplegia and pseudobulbar palsy after CT and MRI documented bilateral thalamo-capsular lesions by neuro-Behçet disease. Single photon emission tomography (SPECT) and Xenon CT revealed hypoperfusion of the bilateral frontal lobes. The pathophysiological mechanism of mutism was discussed and we postulate that mutism might occur as the result of frontal lobe dysfunction due to the disconnection of thalamocortical fiber from thalamus to frontal cortex and that it could be interpreted as an incomplete form of akinetic mutism.

In vitro keratin expression of hair cells.

Human hair follicles were isolated from the scalp by dispase and collagenase treatment and dispersed into a cell suspension by trypsin. These cells proliferated well and could be subcultured 7 to 8 times. The medium used was MCDB 153 HAA medium further supplemented with some amino acids, hydrocortisone, insulin, EGF, and bovine brain extract. The concentration of Ca++ was adjusted to 0.1 mM. Immunohistochemically, these cells were proved to possess keratins specific to hair forming cells.

Monoclonal antibody analysis of keratin expression in carcinomas of sweat glands.

Characteristics of keratins of five carcinomas of sweat gland origin were immunohistochemically investigated with several antikeratin monoclonal antibodies with differing specificities. Specimens were obtained from two cases of mucinous carcinoma of the skin, two cases of classic type of eccrine adenocarcinoma, and a case of eccrine porocarcinoma. The tumor cells of mucinous carcinoma expressed only simple epithelial keratins. In a case of eccrine adenocarcinoma, simple epithelial keratin 19 was diffusely expressed. The expression of the other simple epithelial keratins was confined to the luminal cells, whereas the remaining tumor cells further expressed stratified epithelial keratins. Eccrine porocarcinoma and a second case of eccrine adenocarcinoma did not express simple epithelial keratins, although stratified epithelial keratins were diffusely expressed. These data suggest that carcinomas of sweat glands express various combinations of simple and stratified epithelial keratins. Development of additional data along these lines may help to further define their classification.

[Changes in magnesium and calcium levels in blood and stomach tissue of patients with stomach cancer].

This study was performed to evaluate changes in Magnesium (Mg) and Calcium (Ca) levels in blood and cancerous stomach tissue of patients with stomach cancer, who were classified into four stages of malignancy and three groups of metastatic category. Mg and Ca were determined with atomic absorption spectrophotometer after blood and stomach tissue were digested with nitric and perchloric acid. Significantly high Mg levels in the early stages were found both in plasma and in whole blood. On the other hand, significantly low Ca levels were found in blood plasma in most stages and in all metastatic groups. By contrast, significantly high Ca levels were observed in whole blood in later malignant stages and in two metastatic groups. Significantly high Mg and low Ca levels were found in cancerous stomach tissue in patients with stomach cancer, as compared to their normal stomach tissue. The same tendencies were observed in each malignant stages and metastatic groups. These changes in Mg and Ca levels in blood and cancerous stomach tissue may reflect inherent peculiarities of stomach cancer.