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Hiroyuki Kato

Publications and source records attributed to Hiroyuki Kato.

At least 19 recordsLinked to original sources
PubMed2007

Immunohistochemical study on distribution of NF-kappaB and p53 in gerbil hippocampus after transient cerebral ischemia: effect of pitavastatin.

We investigated the immunohistochemical alterations of the transcription nuclear factor kappa-B (NF-kappaB) and transcription factor p53 in the hippocampus after transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the alterations of NF-kappaB, p53 and neuronal nuclei in the hippocampus after ischemia. Severe neuronal damage was observed in the hippocampal CA1 neurons 5 and 14 days after ischemia. In the present study, the increase of NF-kappaB immunoreactivity in glial cells and p53 immunoreactivity in neurons preceded neuronal damage in the hippocampal CA1 sector after ischemia. Thereafter, NF-kappaB immunoreactivity was induced highly in reactive astrocytes and microglia of the hippocampal CA1 sector where severe neuronal damage was observed. Our immunohistochemical study showed that pitavastatin prevented the alterations of NF-kappaB and p53 in the hippocampal CA1 sector 5 days after transient ischemia. Furthermore, our results with neuronal nuclei immunostaining indicate that pitavastatin dose-dependently prevented the neuronal cell death in the hippocampal CA1 sector 5 days after transient cerebral ischemia. These results suggest that the up-regulations of NF-kappaB in glia and p53 in neurons can cause neuronal cell death after ischemia. Our findings also support the hypothesis that NF-kappaB- and/or p53-mediated neuronal cell death is prevented through decreasing oxidative stress by pitavastatin. Thus, NF-kappaB and p53 may provide an attractive target for the development of novel therapeutic approaches for brain stroke.

Animals↗
PubMed2007

Prognostic significance of EpCAM expression in human esophageal cancer.

EpCAM is a 40-kDa epithelial transmembrane glycoprotein that has a well-known role in Ca2+ -independent homophilic cell-cell adhesion. Recently, correlations between EpCAM expression and clinicopathological features have been investigated in various cancers. We examined EpCAM expression in surgical specimens from esophageal cancer patients (n = 138), using real-time RT-PCR, immunohistochemistry and ELISA. The mean expression level of EpCAM mRNA in tumor tissues was significantly higher than that in corresponding normal tissues (P < 0.0001). Immunohistochemically, positive staining for EpCAM was found in 135 (97.8%) of the 138 primary tumor specimens. EpCAM expression was correlated with tumor depth (P = 0.0005), stage (P = 0.0037), blood-vessel invasion (P = 0.0397) and infiltrative growth pattern (P = 0.0015). The survival rates of patients with tumors with high EpCAM expression was significantly higher than those for patients with tumors with low EpCAM expression (P = 0.0213). Furthermore, the serum EpCAM levels of patients with esophageal cancer were significantly higher than those of normal volunteers (P = 0.0221). The survival rates of patients with a high EpCAM level in the peripheral vein were also significantly higher than those for patients with a low serum EpCAM level (P = 0.0291). The serum EpCAM level in the peripheral vein was independently associated with prognosis (P = 0.0074; hazard ratio 7.40). Tumor-specific EpCAM expression and release into the circulation may serve as effective immunotherapy in esophageal cancer patients.

Aged↗
PubMed2006

Expression of carbohydrate antigens in human esophageal squamous cell carcinoma: prognostic application and its diagnostic implications.

BACKGROUND: Tumor markers whose antigenic determinants have been demonstrated to consist of carbohydrates are probably one of the most extensive tools that have been used in routine cancer diagnosis. In this study, the relevance of carbohydrate antigen expression profile was examined in esophageal squamous cell carcinoma together with prognosis in 130 patients. METHODS: The expression of carbohydrate antigens was estimated immunohistochemically by anti-sialyl Lewis a (sialyl Le(a)) and anti-sialyl Lewis x (sialyl Le(x)) monoclonal antibodies, and correlation between their staining and clinicopathological status was examined. In addition, the correlation of both carbohydrate antigens expression was evaluated with microvessel density (MVD). RESULTS: Expressions of sialyl Lewis antigens and MVD were associated with several clinicopathological features that reflect the tumor aggressiveness in esophageal cancer. The 5-year survival rate of patients was found to be associated with expression of sialyl Le(a) and sialyl Le(x) antigens and with MVD; thus, all of them were revealed to be independent prognostic factors. CONCLUSIONS: Combination of these factors offered a better prediction of prognosis of esophageal squamous cell carcinoma. Further, carbohydrate antigens represent a promising target for therapeutic approaches against the disease.

Aged↗
PubMed2006

Computer-assisted screw insertion for cervical disorders in rheumatoid arthritis.

To reconstruct highly destructed unstable rheumatoid arthritis (RA) cervical lesions, the authors have been using C1/2 transarticular and cervical pedicle screw fixations. Pedicle screw fixation and C1/2 transarticular screw fixation are biomechanically superior to other fixation techniques for RA patients. However, due to severe spinal deformity and small anatomical size of the vertebra, including the lateral mass and pedicle, in the most RA cervical lesions, these screw fixation procedures are technically demanding and pose the potential risk of neurovascular injuries. The purpose of this study was to evaluate the accuracy and safety of cervical pedicle screw insertion to the deformed, fragile, and small RA spine lesions using computer-assisted image-guidance systems. A frameless, stereotactic image-guidance system that is CT-based, and optoelectronic was used for correct screw placement. A total of 21 patients (16 females, 5 males) with cervical disorders due to RA were surgically treated using the image-guidance system. Postoperative computerized tomography and plane X-ray was used to determine the accuracy of the screw placement. Neural and vascular complications associated with screw insertion and postoperative neural recovery were evaluated. Postoperative radiological evaluations revealed that only 1 (2.1%; C4) of 48 screws inserted into the cervical pedicle had perforated the vertebral artery canal more than 25% (critical breach). However, no neurovascular complications were observed. According to Ranawat's classification, 9 patients remained the same, and 12 patients showed improvement. Instrumentation failure, loss of reduction, or nonunion was not observed at the final follow-up (average 49.5 months; range 24-96 months). In this study, the authors demonstrated that image-guidance systems could be applied safely to the cervical lesions caused by RA. Image-guidance systems are useful tools in preoperative planning and in transarticular or transpedicular screw placement in the cervical spine of RA patients.

Aged↗
PubMed2006

Foaming properties of monoglycerol fatty acid esters in nonpolar oil systems.

Foaming properties of monoglycerol fatty acid esters that have different alkyl chain lengths were studied in different nonpolar oils, namely liquid paraffin (LP 70), squalane, and squalene. The effect of the hydrocarbon chain length of the surfactant, the concentration, the nature of the oil, and the temperature on the nonaqueous foam stability was mainly studied. Five weight percent of glycerol alpha-monododecanoate (monolaurin) formed highly stable foams in squalane at 25 degrees C, and the foams were stable for more than 14 h. Foam stability of the monolaurin/LP 70 and the monolaurin/squalene systems are almost similar, and the foams were stable for more than 12 h. Foam stability was decreased as the hydrocarbon chain length of the monoglyceride decreased. In the glycerol alpha-monodecanoate (monocaprin)-oil systems, the foams were stable only for 3-4 h, depending on the nature of the oil. However, the foams formed in the glycerol alpha-monooctanoate (monocaprylin)-oil systems coarsened very quickly, leading to the progressive destruction of foam films, and all of the foams collapsed within a few minutes. Foam stability decreased when the oil was changed from squalane to squalene, in both monocaprin and monolaurin systems. It was observed that, in the dilute regions, these monoglycerides form fine solid dispersions in the aforementioned oils at 25 degrees C. At higher temperatures, the solid melts to isotropic single-liquid or two-liquid phases and the foams formed collapsed within 5 min. Judging from the wide-angle X-ray scattering (WAXS) and the foaming test, it is concluded that the stable foams are mainly caused by the dispersion of the surfactant solids (beta-crystal) and foam stability is largely influenced by the shape and size of the dispersed solid particles.

Journal Article↗
PubMed2006

Calcium-triggered membrane interaction of the alpha-synuclein acidic tail.

Alpha-synuclein (alpha-syn) is a 140-residue protein that aggregates in intraneuronal inclusions called Lewy bodies in Parkinson's disease (PD). It is composed of an N-terminal domain with a propensity to bind lipids and a C-terminal domain rich in acidic residues (the acidic tail). The objective of this study was to examine the effect of Ca(2+) on the acidic tail conformation in lipid-bound alpha-syn. We exploit the extreme sensitivity of the band III fluorescence emission peak of the pyrene fluorophore to the polarity of its microenvironment to monitor subtle conformational response of the alpha-syn acidic tail to Ca(2+). Using recombinant human alpha-syn bearing a pyrene to probe either the N-terminal domain or the acidic tail, we noted that lipid binding resulted in an increase in band III emission intensity in the pyrene probe tagging the N-terminal domain but not that in the acidic tail. This suggests that the protein is anchored to the lipid surface via the N-terminal domain. However, addition of Ca(2+) caused an increase in band III emission intensity in the pyrene tagging the acidic tail, with a corresponding increased susceptibility to quenching by quenchers located in the lipid milieu, indicative of lipid interaction of this domain. Taken together with the increased beta-sheet content of membrane-associated alpha-syn in the presence of Ca(2+), we propose a model wherein initial lipid interaction occurs via the N-terminal domain, followed by a Ca(2+)-triggered membrane association of the acidic tail as a potential mechanism leading to alpha-syn aggregation. These observations have direct implications in the role of age-related oxidative stress and the attendant cellular Ca(2+) dysregulation as critical factors in alpha-syn aggregation in PD.

Adenosine↗
PubMed2006

Hypertension downregulates the expression of brain-derived neurotrophic factor in the ischemia-vulnerable hippocampal CA1 and cortical areas after carotid artery occlusion.

We studied the effect of hypertension on brain damage and brain-derived neurotrophic factor (BDNF) expression in the hippocampal formation and cerebral cortex after permanent occlusion of bilateral common carotid arteries (CCA). Two groups of rats were used, including normotensive Wistar-Kyoto (WKY) rat and spontaneous hypertensive rat (SHR). Each group contained sham operation, 1 week and 4 weeks after bilateral CCA occlusion (n=5-10 in each time point). The blood pressure showed a significant elevation in WKY rats from 1 h after operation to 4 weeks before sacrifice (P<0.05), but was not changed in SHR (P>0.05). However, rectal temperature showed no significant change after operation in WKY rat and SHR (P>0.05) and showed no significant difference at any time point between WKY rat and SHR (P>0.05). Hematoxylin and eosin staining showed SHR had a significantly larger necrotic volume than WKY rats (n=10 in each group, 6044+/-6895 microm(3) vs. 144+/-174 microm(3), P<0.05) at 4 weeks after ischemia. In SHR, BDNF immunoreactivity and mRNA decreased significantly from 1 week to 4 weeks in both the hippocampal CA1 and cortical areas (P<0.01) but decreased transiently in dentate gyrus. However, in WKY rats, BDNF immunoreactivity and mRNA decreased transiently at 1 week (P<0.05) and recovered at 4 weeks after cerebral ischemia. Our study demonstrates that after bilateral CCA occlusion, preexisting hypertension may aggravate the brain injury and downregulate the expression of BDNF immunoreactivity and mRNA in the ischemia-vulnerable hippocampal CA1 and cortical areas but not in ischemia-resistant dentate gyrus.

Animals↗
PubMed2006

Allelic gene regulation of Pcdh-alpha and Pcdh-gamma clusters involving both monoallelic and biallelic expression in single Purkinje cells.

The molecular basis for providing the identity and diversity of single neurons is a key for realizing the brain system. Diverse protocadherin isoforms encoded by the Pcdh-alpha and Pcdh-gamma gene clusters are expressed in all of the vertebrates studied. For the Pcdh-alpha isoforms, differential expression patterns have been found in single Purkinje cells by unusual monoallelic and combinatorial types of gene regulation. Here we investigated total allelic gene regulation in the Pcdh-alpha and -gamma clusters, including the C-type variable exons (C1 to C5) and the Pcdh-gammaA and -gammaB variable exons in single Purkinje cells. Using split single-cell reverse transcription-PCR analysis, almost all of the Purkinje cells at postnatal day 21 biallelically expressed all the C-type isoforms, whereas the Pcdh-alpha isoforms showed both monoallelic and combinatorial expression. The Pcdh-gammaA and -gammaB isoforms also showed differential regulation in each cell with both monoallelic and combinatorial gene regulation. These data indicated that different types of allelic gene regulation (monoallelic versus biallelic) occurred in the Pcdh-alpha and -gamma clusters, although they were spliced into the same constant exons. It has been reported that each C-type Pcdh-alpha or -gamma transcript has a different expression pattern during brain development, suggesting that the different C-type variable exons may code temporal diversity, although the Pcdh-alpha, -gammaA, and -gammaB isoforms were differential and combinatorial gene regulation within a single cell. Thus, the multiple gene regulations in the Pcdh-alpha and -gamma clusters had a potential mechanism for increasing the diversity of individual neurons in the brain.

Alleles↗
PubMed2006

Lack of activated Smad2 in transforming growth factor-beta signaling is an unfavorable prognostic factor in patients with esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Transforming growth factor-beta (TGF-beta) regulates cell growth in various cells, and inactivation of the TGF-beta-signaling pathway contributes to tumor progression. In this study, we investigated the expression of Smad2 and Smad3, which are specific intracellular mediators of TGF-beta signaling. We also examined the relationship between the expression levels of activated Smad2 by TGF-beta and clinicopathologic characteristics of patients with esophageal squamous cell carcinoma (SCC). METHODS: Immunohistochemical staining with anti-phosphorylated Smad2 (P-Smad2) polyclonal antibody, anti-Smad2 monoclonal antibody, and anti-Smad3 polyclonal antibody was performed on surgical specimens obtained from 80 patients with esophageal SCC. RESULTS: Our data indicated that a low level of P-Smad2, as detected immunohistologically, correlated with lymph node metastasis (P = 0.0002), distant metastasis (P = 0.0338), pathologic stage (P = 0.0093), and poor survival rate (P = 0.0246). All patients without positive Smad2 immunostaining were included among those without positive P-Smad2 immunostaining. There was no significant correlation between expression of Smad2 or Smad3 and clinicopathologic characteristics. CONCLUSIONS: We demonstrated that a lack of Smad2-P appears to be correlated with tumor development and poor prognosis in patients with esophageal SCC.

Adult↗
PubMed2006

Usefulness of white blood cell differential for early diagnosis of surgical wound infection following spinal instrumentation surgery.

STUDY DESIGN: The white blood cell (WBC) count and WBC differential were measured prospectively in patients after spinal instrumentation surgery with or without surgical wound infection. OBJECTIVES.: To investigate the usefulness of WBC differential for early diagnosis of surgical wound infection after spinal instrumentation surgery. SUMMARY OF BACKGROUND DATA: Renewed elevation of C-reactive protein (CRP) or WBC, gallium scan, and CRP/transthyretin mass concentration ratio were reported for early diagnosis of surgical wound infection. METHODS: A total of 39 patients were enrolled in this study: 13 patients who developed wound infection within 2 weeks after spinal instrumentation surgery (infection group) and 26 patients who were comparable with those patients included in the infection group with regard to age, sex, and surgical techniques used (control group). The WBC count and WBC differential were determined before and after surgery. RESULTS: In both groups, WBC and percentage and number of neutrophils showed nearly same change until postoperative 4 days (day 4). However, in the infection group, these parameters had increased after day 4. In both groups, the percentage and number of lymphocytes decreased to 10% or less and 1,000/microL or less on day 1, respectively. These lymphocyte parameters began to gradually normalize on day 4 and returned to the preoperative level 3 weeks after surgery in the control group. On the other hand, these parameters remained 10% or less and 1,000/muL or less until day 11 in the infection group. In patients with infection, the percentage and number of lymphocytes significantly decreased as early as on day 4. CONCLUSION: Lymphopenia represents immunodepression status, thus indicating the increased susceptibility to infection, which may lead to the development of postoperative infection. If lymphopenia is diagnosed as early as possible, surgical wound infection can be treated promptly without removing the instruments.

Adolescent↗
PubMed2006

Autologous osteochondral mosaicplasty for capitellar osteochondritis dissecans in teenaged patients.

BACKGROUND: Autologous osteochondral mosaicplasty is a new technique to provide hyaline repair for articular defects. Although recent studies have reported the successful treatment of articular defects in the knee and ankle joints with this surgical procedure, little attention has been given to the surgical efficacy of mosaicplasty in the treatment of osteochondritis dissecans of the humeral capitellum. PURPOSE: To clarify the clinical outcomes of mosaicplasty for teenaged patients with advanced lesions of capitellar osteochondritis dissecans. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Eight teenaged patients with advanced lesions of capitellar osteochondritis dissecans underwent mosaicplasties. All patients were baseball players who were affected on the right side, which was also their throwing side. The surgical technique involves obtaining small-sized cylindrical osteochondral grafts from the lateral periphery of the femoral condyles and transplanting them to prepared osteochondral defects. At a mean follow-up of 24 months, all patients were evaluated clinically and radiographically. RESULTS: Seven of the 8 patients were free from elbow pain, and the remaining patient had mild pain occasionally. The mean clinical score described by Timmerman and Andrews (a maximum of 200 points) significantly improved from 140 points to 183 points postoperatively. All patients except one had excellent or good clinical results. Radiographically, the graft incorporation and a normal contour of the subchondral cortex were found in all patients. Magnetic resonance imaging showed that the preoperative heterogeneity of the lesion had disappeared and the signal intensity returned to normal. Six of the 8 patients, including all 3 pitchers, returned to competitive-level baseball. CONCLUSION: Mosaicplasty for advanced lesions of capitellar osteochondritis dissecans in teenaged baseball players can provide satisfactory clinical and radiographic results.

Adolescent↗
PubMed2006

A novel technique to facilitate laparoscopic repair of large paraesophageal hernias.

BACKGROUND: Laparoscopic repair of large paraesophageal hernias (LPEH) is technically challenging, and requires advanced laparoscopic skills. We have developed a novel technique for facilitating laparoscopic repair of LPEHs safely and easily, using a Nelaton catheter. PATIENTS AND METHODS: Seven patients with LPEHs were operated on through a laparoscopic approach. During surgery, the left lobe of the liver and right diaphragmatic crus were elevated using a suspended thread covered by a Nelaton catheter. RESULTS: All patients were operated on laparoscopically using this technique. No patient required conversion to open method. The median operating time was 205 minutes and the range was from 155 to 295 minutes. No intraoperative or early complications occurred in any patient. Late complications occurred in 2 patients due to a small sliding hernia: a slipped fundoplication in 1 patient, and a gastric ulcer in the other. CONCLUSIONS: In conclusion, laparoscopic repair of LPEH is a challenging procedure that requires wide experience in laparoscopic gastroesophageal surgery. Further refinement for this operation may be necessary.

Aged↗
PubMed2006

Stabilization of the proximal ulnar stump in the Sauvé-Kapandji procedure by using the extensor carpi ulnaris tendon: long-term follow-up studies.

PURPOSE: The Sauvé-Kapandji procedure is considered a useful treatment option for distal radioulnar disorders. Postoperative instability of the proximal ulnar stump and radioulnar convergence, however, may be symptomatic. We modified the Sauvé-Kapandji procedure by stabilizing the proximal ulnar stump with a half-slip of the extensor carpi ulnaris tendon. We previously reported on 13 patients with this procedure at an average follow-up period of 35 months; the patients had satisfactory clinical results and improved stability of the proximal ulnar stump as shown by x-ray examination. In this article we address the question of whether those clinical and radiographic results noted at an average follow-up period of 35 months after surgery were maintained at later follow-up examinations. METHODS: We re-examined 12 of the 13 original patients and compared their initial follow-up results with their current results after an average follow-up period of 95 months. RESULTS: The results of this series after 95 months of follow-up evaluation were similar to the results at 35 months. CONCLUSIONS: The results presented in this article suggest that the clinical radiographic results at the 35-month follow-up examination were maintained in the long-term 95-month follow-up evaluation despite the finding that the hole in the proximal ulnar stump had broken in 3 wrists at follow-up examination. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

Adult↗
PubMed2006

Modulations of muscle protein metabolism by branched-chain amino acids in normal and muscle-atrophying rats.

It has been shown that BCAAs, especially leucine, regulate skeletal muscle protein metabolism. However, it remains unclear how BCAAs regulate muscle protein metabolism and lead to anabolism in vivo. We examined muscle protein synthesis rate and breakdown rate simultaneously during BCAA infusion in muscle atrophy models as well as in normal healthy rats. Corticosterone-treated rats and hindlimb-immobilized rats were used as muscle atrophy models. Muscle protein synthesis rate and breakdown rate were measured as phenylalanine kinetics across the hindlimb. In anesthetized normal rats, BCAAs stimulated muscle protein synthesis despite low insulin concentration and did not suppress muscle protein breakdown. In corticosterone-treated rats, BCAAs failed to restore inhibited muscle protein synthesis, but reduced muscle protein breakdown. Immobilization of hindlimb increased muscle protein breakdown within a day. BCAAs did not change muscle protein metabolism, although essential amino acids (EAAs) suppressed muscle protein breakdown in hindlimb-immobilized rats. We also evaluated changes of fractional synthesis rate (FSR) of skeletal muscle protein during infusion of leucine alone or EAAs for 4 h in anesthetized normal rats. FSR showed a transient increase at 15-30 min of leucine infusion and then declined, whereas FSR stayed elevated throughout EAA infusion. We concluded that 1) BCAAs primarily stimulate muscle protein synthesis in normal rats independently of insulin; 2) EAAs are required to maintain the BCAA stimulation of muscle protein synthesis; and 3) The effects of BCAAs on muscle protein metabolism differ between atrophy models.

Amino Acids, Branched-Chain↗
PubMed2006

Prolyl isomerase Pin1 expression predicts prognosis in patients with esophageal squamous cell carcinoma and correlates with cyclinD1 expression.

Esophageal carcinoma is one of the most lethal tumors, and identification of prognostic factors for patients with this disease is important. Propyl isomerase Pin1 is overexpressed in some human cancers and thought to be an important regulator of cyclinD1. However, the relationships between Pin1 expression and clinicopathologic features in patients with esophageal squamous cell carcinoma (SCC) have not been explored. Here, we investigated the role of Pin1 in association with cyclinD1 in esophageal SCC progression and its clinicopathological significance. The expressions of Pin1 and cyclinD1 were examined immunohistochemically in surgical specimens from 119 esophageal SCC patients. The expression levels of Pin1 and cyclinD1 in 6 esophageal SCC-derived cell lines were compared with those in an immortalized human esophageal cell line by western blotting. Pin1 overexpression was correlated with lymph node metastasis (P=0.0384), and its expression was related to cyclinD1 expression. Pin1 expression was correlated with poor prognosis in esophageal SCC patients (P=0.0044), and found to be an independent prognostic factor (P=0.0277). Pin1 was overexpressed in 5 of 6 esophageal SCC-derived cell lines compared with immortalized esophageal keratinocytes. Moreover, the Pin1 level was correlated with the cyclinD1 level in 4 of the 6 cell lines. In conclusion, Pin1 expression is correlated with cyclinD1 expression and may be a useful prognostic factor for esophageal SCC.

Adult↗
PubMed2005

Neuroprotective effect of arundic acid, an astrocyte-modulating agent, in mouse brain against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes the damage of dopaminergic neurons as seen in Parkinson's disease. Oxidative stress has been as one of several pathogenic hypotheses for Parkinson's disease. Here we investigated whether arundic acid, an astrocyte-modulating agent, can protect against alterations of nitric oxide synthase (NOS) and superoxide dismutase (SOD) expression on MPTP neurotoxicity in mice, utilizing an immunohistochemistry. For this purpose, anti-tyrosine hydroxylase (TH) antibody, anti-dopamine transporter (DAT) antibody, anti-Cu/Zn-SOD antibody, anti-Mn-SOD antibody, anti-nNOS antibody, anti-eNOS antibody and anti-iNOS antibody were used. The present study showed that the arundic acid had a protective effect against MPTP-induced neuronal damage in the striatum and substantia nigra of mice. The protective effect may be, at least in part, caused by the reductions of the levels of reactive nitrogen (RNS) and oxygen species (ROS) against MPTP neurotoxicity. These results suggest that the pharmacological modulation of astrocyte may offer a novel therapeutic strategy for the treatment of Parkinson's disease. Furthermore, our results provide further evidence that a combination of nNOS inhibitors, iNOS inhibitors and free radical scavengers may be effective in the treatment of neurodegenerative diseases. Thus our present results provide valuable information for the pathogenesis of degeneration of the nigrostriatal dopaminergic neuronal pathway.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2005

Ehlers-Danlos syndrome type VIB with characteristic facies, decreased curvatures of the spinal column, and joint contractures in two unrelated girls.

Two unrelated girls, aged 11 and 14 years, with clinical manifestations of Ehlers-Danlos syndrome (EDS) type VIB, characteristic facies, skeletal abnormalities, and other features are described. They had Marfanoid habitus with pectus excavatum; fragile, hyperextensible, and readily bruisable skin with widened, atrophic scars; recurrent hematomas; generalized joint laxity; hypotonia; scoliosis; and mild delay of gross motor development. Lysyl hydroxylase deficiency was ruled out in Patient 1. Parental consanguinity was present in Patient 2. They both had, in early childhood, down-slanting palpebral fissures, drooping lower eyelids, short nose, small mouth, and long philtrum. Facial features that persisted included thick eyebrows, hypertelorism, strabismus, blue sclerae, low-set, and slanted ears, hypoplastic columella, high-arched palate, and thin upper lip. They had tubular stenosis of the phalanges, metacarpals, and metatarsals; decreased physiological curvatures of the spinal column with tall vertebrae; and joint contractures including talipes equinovarus and progressive talipes valgus. Their hearing of high-pitched sounds was impaired. They had constipation and recurrent cystitis with an enlarged bladder. In view of these findings, we propose that these two girls represent a clinically recognizable subgroup of EDS type VIB.

Adolescent↗