Primary orbital melanoma in a child.
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Child↗
Biomedical subjects
D Ito
Publications and source records attributed to D Ito.
Persistent CREB phosphorylation with protection of hippocampal CA1 pyramidal neurons following temporary occlusion of the middle cerebral artery in the rat.
Phosphorylation of the DNA-binding transcription factor, cyclic AMP response element binding protein (CREB), was immunohistochemically examined in rat brain hippocampal CA1 in order to examine the ischemic vulnerability of this region from the viewpoint of CREB activation. The rat brain had been subjected to 90-min focal ischemia followed by various periods of recirculation. Focal ischemia was induced by occlusion of the middle cerebral artery using the intraluminal suture method. CA1 pyramidal neurons in the sham animals showed definite immunoreactivity with anti-CREB antibody, which binds to both unphosphorylated and phosphorylated CREB, while reactivity with anti-phosphorylated CREB antibody was barely detectable in these neurons. In contrast, at 3.5 h of recirculation, a significant increase in the number of phosphorylated CREB-positive neurons was noted in the CA1 on both sides, and the increase continued until 48 h of recirculation with a tendency for gradual decline. At each period, the ischemic side showed a more marked increase in the number of immunoreactive cells as compared to the nonischemic side. Cresyl violet staining revealed CA1 pyramidal neurons to be maintained intact until 14 day of recirculation, at which time CREB phosphorylation has returned to the control level. Transient global ischemia is known to induce only mild CREB phosphorylation in the CA1 followed by a frank neuronal loss in this region. These data suggest that CREB phosphorylation can be persistently activated in CA1 neurons after focal ischemia and that this phenomenon may be closely associated with protection of these neurons.
Animals↗
Hyalinosis cutis et mucosae: a case report.
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Adolescent↗
Effective priming of cytotoxic T lymphocyte precursors by subcutaneous administration of peptide antigens in liposomes accompanied by anti-CD40 and anti-CTLA-4 antibodies.
Recently it has been shown that modulation of CD40 molecules on antigen (Ag) carrying dendritic cells (DC) can bypass T cell help, resulting in priming cytotoxic T lymphocytes (CTL) specific for the Ag. In the present study we attempted to prime peptide Ag-specific CTL by a new method in which a peptide Ag in liposome (liposomal peptide), consisting of phosphatidylserine and phosphatidylcholine (3:7), was administrated subcutaneously with anti-CD40 and/or CTLA-4 monoclonal antibodies (mAb) to mice. We found that the subcutaneous administration of the liposomal peptide with both anti-CD40 and anti-CTLA-4 mAb enhanced CTL responses comparing with those induced by the liposomal peptide alone or the liposomal peptide plus each mAb. It was shown that liposomes were critical for induction of the CTL activity. Flow cytometry analysis of a peptide-bearing DC in lymph nodes (LN) and measurement of serum IL-12 indicated that anti-CD40 mAb promoted migration of DC to the LN, where DC might differentiate and acquire ability of priming CTL. These findings provide a possibility that our procedure is applicable to cancer patients.
Abatacept↗
Activated phosphorylation of cyclic AMP response element binding protein is associated with preservation of striatal neurons after focal cerebral ischemia in the rat.
Phosphorylation of the DNA-binding transcription factor, cyclic AMP response element binding protein, has recently been suggested to provide neuroprotective signals in times of cellular stress. Medium-sized striatal neurons are among the cells that are most vulnerable to ischemic stress in the brain. In the present study, phosphorylation of cyclic AMP response element binding protein was immunohistochemically evaluated in rat striatum in order to examine the ischemic vulnerability of each striatal region from the standpoint of cyclic AMP response element binding protein. Rats were subjected to 90-min focal cerebral ischemia followed by various periods of recirculation. Focal ischemia was induced by occlusion of the middle cerebral artery by the intraluminal suture method. Local cerebral blood flow measured by the 14C-iodoantipyrine method in the lateral and the medial striatal regions during occlusion was 5.0+/-7. 1 and 42.5+/-8.1ml/100g/min, respectively. Cerebral blood flow in each region was restored to the control level during the recirculation period. The lateral and the medial regions of the striatum in the sham animals showed hardly any immunoreactivity with the specific antibody against phosphorylated cyclic AMP response element binding protein. By contrast, at 3.5h of recirculation, a number of phosphorylated cyclic AMP response element binding protein-positive neurons were detected in the medial striatal region on the occluded side, and the increase in the number of immunopositive cells continued until two weeks of recirculation with gradual decline. The lateral striatal region on the ischemic side showed only a mild increase in phosphorylated cyclic AMP response element binding protein-positive cells at 3.5h of recirculation, and the immunoreactivity rapidly disappeared during the subsequent recirculation period. Appreciable increase in immunoreactive cells was also noted in the contralateral striatum during the early phase of recirculation, and this increase seemed to be associated with spontaneous circling movements of the animals. Cresyl Violet staining revealed that striatal neurons in the medial region remained intact until two weeks of recirculation, whereas neurons in the lateral striatal region soon showed ischemic damage, followed by complete neuronal loss, and evolution of a frank infarct. Immunoreactivity for bcl-2, apoptosis-suppressive protein, was clearly detected in many neurons in the medial striatal region, but no such immunoreactivity was detected in the lateral striatal region. These findings suggest that persistently activated phosphorylation of cyclic AMP response element binding protein in the striatum during post-ischemic recirculation may be closely associated with protection of striatal neurons on the ischemic side, while it may be associated with spontaneous circling movements on the contralateral side.
Animals↗
Protean manifestations of lipoid proteinosis in a 16-year-old boy.
We report a 16-year-old Japanese male with lipoid proteinosis showing various skin manifestations. The patient was born to nonconsanguineous parents and none of his relatives was similarly affected. The patient suffered from a hoarse voice and refractory temporal epilepsy from early childhood. Computed tomography scanning of the brain showed bilateral calcification in the temporal lobes, a characteristic feature of lipoid proteinosis. On physical examination, various skin manifestations, including papules and haemorrhagic blisters, acne-like scars at sites of minor trauma or friction, and beads of small papules along the free margins of the eyelids were noted. A skin biopsy showed deposits of homogeneous hyaline-like material, positive on periodic acid-Schiff staining, throughout the dermis, particularly around small blood vessels. It is noteworthy that a range of characteristic skin lesions can be present in a patient with lipoid proteinosis even with mild systemic involvement.
Adolescent↗
Long-term effects nasal continuous positive airway pressure on daytime sleepiness, mood and traffic accidents in patients with obstructive sleep apnoea.
To describe the long-term effects of nasal continuous positive airway pressure (CPAP) on the rate of traffic car accidents, excessive daytime sleepiness (EDS) and mood in patients with obstructive sleep apnoea syndrome (OSAS), we investigated the changes of these parameters before and after nasal CPAP treatment using a questionnaire. Seventy-five male patients who were diagnosed with severe OSAS by polysomnography were evaluated for driving competence, by looking at their driving history for 2 yr, for EDS by the Epwarth Sleepiness Scale (ESS) and for mood by the Self-related Depression Scale (SDS), and then underwent nasal CPAP treatment. After 2 yr of treatment, questionnaires inquiring about the patients' use of CPAP, their ESS, SDS and driving history during treatment were sent to the patients. A total of 47 patients (63%) responded to these questionnaires. Forty-six of the 47 responders had continued to use the nasal CPAP and completed the questionnaire. No traffic car accidents were observed among the 39 routine car users during treatment, while 13 of 39 patients (33%) had had car accidents before treatment. Although near-miss accidents had been reported by 32 of 39 patients (82%) before treatment, only four patients reported near-miss accidents during nasal CPAP treatment. The mean score of ESS was significantly (P<0.01) reduced in 46 patients after nasal CPAP. The mean score of SDS was also decreased (P<0.01) after nasal CPAP in 46 patients. Although 26 of 41 patients had been depressive on SDS before treatment, the mood was improved in 13 patients after nasal CPAP. These results suggest that long-term nasal CPAP treatment reduces the rate of traffic car accidents and improves the EDS and the mood in patients with OSAS.
Accidents, Traffic↗
Immunohistochemical detection of leukemia inhibitory factor after focal cerebral ischemia in rats.
The cytokine leukemia inhibitory factor (LIF) modulates neuronal function during development and promotes neuronal survival after peripheral nerve injury, but little is known about LIF expression after cerebral ischemia. In the present study, the localization of LIF protein was immunohistochemically examined in rats after 3.5, 12, 24, 48, and 96 hours of reperfusion following 1.5 hours of middle cerebral artery occlusion (MCAO) induced by the intraluminal suture method. Double-staining immunohistochemistry with microtubule-associated protein-2 (MAP2), glial fibrillary acidic protein (GFAP), lectin histochemistry, and interleukin (IL) 6 was also performed. The sham group and immunosorption test did not show any clear LIF immunoreactivity. Definite LIF immunoreactivity was first detected after 12 hours of reperfusion in each of the brain regions examined: ischemic core, periinfarct region, and contralateral cortex. However, expression of LIF was most prominent in the periinfarct region at each time point, peaked at 24 hours, and then gradually declined until 96 hours of reperfusion. Some LIF-positive neurons in the periinfarct region expressed IL-6. At 96 hours of reperfusion, GFAP-labeled astrocytes around the infarct core also expressed LIF protein. Induction of LIF mRNA and protein was also confirmed by reverse transcription polymerase chain reaction and western blot analysis, respectively. These findings suggest that LIF expression in ischemically threatened neurons may reflect a repair or defense mechanism against the ischemic insult.
Animals↗
Polymorphism in the promoter of lipopolysaccharide receptor CD14 and ischemic cerebrovascular disease.
BACKGROUND AND PURPOSE: A growing amount of evidence suggests that infectious and inflammatory processes may be involved in the initiation of arteriosclerosis, but the mechanisms are conceivably multifactorial and complex. Two European groups have recently demonstrated that a C(-260)-->T polymorphism in the promoter of the CD14 lipopolysaccharide receptor may be a risk factor for coronary artery disease (CAD). The T allele of this polymorphism reportedly increases the expression of CD14 and may be involved in atherogenesis. In the present study we investigated a possible association between the C(-260)-->T polymorphism in the CD14 promoter and the occurrence of symptomatic ischemic cerebrovascular disease (CVD). METHODS: Genotype frequencies of the C(-260)-->T polymorphism in the CD14 promoter were determined in 235 patients with CVD, as confirmed by brain CT and/or MRI, and 309 age- and sex-matched control subjects. RESULTS: The distribution of genotypes was as follows: CVD patients, T:/T: 24.3%, C:/T: 53.2%, and C:/C: 22. 6%; controls, T:/T: 26.9%, C:/T: 50.2%, and C:/C: 23.0%. There was no significant difference between the CD14 promoter genotypes of the CVD patients and the controls (chi(2)=0.601, P:=0.741). We also measured the concentration of serum soluble CD14 and the density of membranous CD14 on monocytes in the CVD patients, but the polymorphism was not associated with either the concentration of soluble CD14 or the density of membranous CD14 (P:=0.358, P:=0.238, respectively). CONCLUSIONS: Our results indicate that the C(-260)-->T polymorphism in the CD14 promoter is not associated with an increased risk for CVD.
Cerebrovascular Disorders↗
Association between platelet glycoprotein Ibalpha genotype and ischemic cerebrovascular disease.
BACKGROUND AND PURPOSE: Platelets play pivotal roles in the development of ischemic cerebrovascular disease (CVD). The platelet glycoprotein (GP) Ib/IX/V complex is a receptor for von Willebrand factor, which plays a major role in the initial phase of platelet activation under high shear stress conditions. This study was designed to investigate the association between a genetic variation of this receptor and the prevalence of CVD. METHODS: Two hundred patients with ischemic CVD, as confirmed by brain CT and/or MRI, and 317 age- and sex-matched control subjects without clinical evidence of CVD or cardiovascular disease were analyzed for their genotype frequencies of the (145)Thr/Met dimorphism of the alpha-chain of GPIb (GPIbalpha). RESULTS: Genotypes with (145)Met (T/M and M/M) were more frequently found in the CVD patients (26.5%) than in control subjects (14.2%, P=0.0005). The genotype effect was more obvious in those <60 years of age or without acquired cardiovascular risk factors. The odds ratio for nonsmoking women <60 years of age was 10. 6 (95% confidence intervals, 2.2 to 51.7). Although the number of patients studied was small (n=24), transient ischemic attack showed the highest odds ratio (4.3, P=0.0004), followed by lacunar infarction (OR=2.2, P=0.0024) and atherothrombotic infarction (OR=1. 5, P=0.3143). Logistic regression analysis revealed that the presence of Met-allele was independently associated with CVD. CONCLUSIONS: Our study suggests that the platelet GPIbalpha genotype is a genetic risk factor for ischemic CVD.
Alleles↗
C242T polymorphism of NADPH oxidase p22 PHOX gene and ischemic cerebrovascular disease in the Japanese population.
BACKGROUND AND PURPOSE: Superoxide has been implicated in the pathogenesis of ischemic stroke and atherosclerosis. NADPH oxidase, a major source of superoxide generation in neutrophils and the vascular system, plays a critical role in ischemic injury and atherogenesis. Recently, an association between the C242T polymorphism of p22 PHOX, an essential component of NADPH oxidase, and coronary artery disease (CAD) has been reported in several studies. To investigate the relationship between the C242T polymorphism of p22 PHOX and ischemic cerebrovascular disease (CVD), we conducted a case-control study. METHODS: We recruited 226 CVD patients (atherothrombotic infarction, lacunar infarction, and transient ischemic attack) and 301 control subjects and analyzed C242T polymorphism of p22 PHOX by detection of restriction fragment length polymorphism. RESULTS: The TC+TT genotype frequencies in the CVD group and control group were 21.7% and 13.3%, respectively, and the prevalence of the TC+TT genotype was significantly higher in the CVD patients (chi(2)=6.477, P=0.01, OR 1.81, 95% CI 1.15 to 2.86). Analysis by CVD subtypes showed that the OR for the TC+TT genotype was higher in the CVD patients with atherothrombotic infarction than in those with lacunar infarction and transient ischemic attack. CONCLUSIONS: The C242T polymorphism of the NADPH oxidase p22 PHOX gene is a novel pathogenetic risk factor for CVD.
Asian People↗
Refolding of denatured/reduced lysozyme at high concentration with diafiltration.
Refolding of reduced and denatured protein in vitro has been an important issue for both basic research and applied biotechnology. Refolding at low protein concentration requires large volumes of refolding buffer. Among various refolding methods, diafiltration is very useful to control the denaturant and red/ox reagents in a refolding solution. We constructed a refolding procedure of high lysozyme concentration (0.5-10 mg/ml) based on the linear reduction of the urea concentration during diafiltration under oxygen pressure. When the urea concentration in the refolding vessel was decreased from 4 M with a rate of 0.167 M/h, the refolding yields were 85% and 63% at protein concentrations, 5 mg/ml and 10 mg/ml, respectively, after 11 h. This method gave a high productivity of 40.1,microM/h of the refolding lysozyme. The change in refolding yields during the diafiltration could be simulated using the model of Hevehan and Clark.
Animals↗
Genotype distribution of the 46C/T polymorphism of coagulation factor XII in the Japanese population: absence of its association with ischemic cerebrovascular disease.
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Aged↗
Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects.
Coagulation factor XII (FXII) is activated on contact with various biologic surfaces, including subendothelial tissues and lipoprotein particles. Thus, the plasma level of activated FXII (XIIa) might represent vascular lesions or be a marker of abnormal lipid metabolism. A 46C/T polymorphism was recently described in the FXII gene close to the ATG translation initiation codon, which was associated with inter-individual variation of plasma FXII zymogen levels. The present paper reports the association of the 46C/T polymorphism with plasma XIIa levels in apparently healthy subjects, and in patients with ischemic cerebrovascular disease (CVD) and arteriosclerosis obliterans (ASO). XIIa levels were not significantly different between patients and controls, but were strongly dependent on XII 46C/T genotypes (2.07 +/- 0.81, 1.65 +/- 0.63, and 0.93 +/- 0.41 ng/ml for C/C, C/T, and T/T genotypes, respectively; P < 0.0001). This association was evident for each group studied (P < 0.0001 for CVD and controls; P= 0.0007 for ASO). There were positive correlations between plasma FXII clotting activity and XIIa levels. In a univariate analysis, XIIa correlated with total cholesterol, triglycerides, plasminogen activator inhibitor-1, and C-reactive protein (CRP), although the presence of conventional cardiovascular risk factors (male sex, smoking, hypertension, hypercholesterolemia, diabetes) did not significantly increase XIIa. Stepwise regression analyses revealed that the XII clotting activity had the strongest association with XIIa. In conclusion, XIIa levels depended on XII 46C/T genotype and correlated with some cardiovascular risk factors. Thus, the FXII genotype should be taken into consideration for interpretation of plasma XIIa levels.
Aged↗
A case of poorly differentiated hilar lung adenocarcinoma of an unidentified histological type.
The patient was a 74-year-old man, a physician, whose chief complaint was an unproductive cough. The shadow of a mass was seen at the hilum of the left lung, and the mediastinal lymph nodes on both sides were swollen. No histological diagnosis was obtained even after bronchoscopy, including transbronchial needle aspiration biopsy, but large-cell carcinoma of the lung was diagnosed on the basis of ultrasound-guided biopsy of a shadow in the liver suspected of being a metastatic tumor (T2N3M1, Stage IV). Two courses of chemotherapy (CBCDA + VDS) failed to gain any improvement, and the pain resulting from recurrent bone metastases was managed mainly by the administration of the best supportive care. The patient was readmitted to the hospital after development of numbness in the right upper extremity followed by complication of pneumonia and heart failure, and he passed away. Autopsy revealed a primary hilar lung tumor with a histological diagnosis of poorly differentiated adenocarcinoma.
Adenocarcinoma↗
Uncoupling of cerebral blood flow and glucose utilization in the regenerating facial nucleus after axotomy.
Axotomy is known to activate various metabolic processes including protein synthesis and glucose utilization in the motor nucleus. Although it is generally assumed that the local cerebral blood flow (CBF) fluctuates in response to the axonal reaction, there has been no direct evidence for changes in CBF in the motor nucleus following axotomy. In this study, the CBF in the facial nuclei was measured after axotomy of the facial nerve employing the [14C]iodoantipyrine method to evaluate the relation between the CBF and axonal reaction. Following unilateral facial nerve axotomy in neonates, which induced neuronal degeneration in the facial nucleus, the CBF and glucose uptake was significantly decreased on the operated nucleus, suggesting that CBF and glucose metabolism are coupled in the degenerating nucleus. In contrast, after axotomy in adults, which induced regeneration of neurons and glial reactions, glucose uptake was increased on the operated nucleus, while the CBF did not differ significantly between the operated and unoperated nucleus. These findings imply that glucose metabolism and CBF are uncoupled in the regenerating nucleus, suggesting that the relation between CBF and metabolism in the regenerating nucleus following axotomy may clearly contradict the classical concept of a tight coupling between CBF and metabolism.
Animals↗
Mice with a targeted mutation in lymphotoxin-alpha exhibit enhanced tumor growth and metastasis: impaired NK cell development and recruitment.
Mice deficient in lymphotoxin (LT)-alpha lack peripheral lymph nodes and Peyer's patches and have profound defects in development of follicular dendritic cell networks, germinal center formation, and T/B cell segregation in the spleen. Although LTalpha is known to be expressed by NK cells as well as T and B lymphocytes, the requirement of LTalpha for NK cell functions is largely unknown. To address this issue, we have assessed NK cell functions in LTalpha-deficient mice by evaluating tumor models with known requirements for NK cells to control their growth and metastasis. Syngeneic B16F10 melanoma cells inoculated s.c. grew more rapidly in LTalpha-/- mice than in the wild-type littermates, and the formation of experimental pulmonary metastases was significantly enhanced in LTalpha-/- mice. Although LTalpha-/- mice exhibited almost a normal total number of NK cells in spleen, they showed an impaired recruitment of NK cells to lung and liver. Additionally, lytic NK cells were not efficiently produced from LTalpha-/- bone marrow cells in vitro in the presence of IL-2 and IL-15. These data suggest that LTalpha signaling may be involved in the maturation and recruitment of NK cells and may play an important role in antitumor surveillance.
Animals↗
Cerebral neurons express interleukin-6 after transient forebrain ischemia in gerbils.
Markedly increased interleukin-6 (IL-6) mRNA levels occur in experimental cerebral ischemia, although the protein production and cellular sources of IL-6 remain unclear. We examined the cellular localization of IL-6 protein in gerbil brain following transient forebrain ischemia employing immunohistochemistry and Western blot analysis. The ischemia/recirculation groups revealed distinct IL-6 immunoreactivity predominantly in cortical and hippocampal neurons after 3 hours to 3 days recirculation. At 12 h recirculation, the IL-6 expression declined specifically in the hippocampus CA1. Microglia, but not activated astrocytes, also expressed IL-6 immunoreactivity. The sham group showed no apparent immunoreactivity. IL-6 protein may thus be expressed mainly in neurons following transient forebrain ischemia. Its transient decline in the CA1 at 12 h recirculation could reflect the specific vulnerability of this region.
Animals↗