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Biomedical subjects

H Nakajima

Publications and source records attributed to H Nakajima.

At least 109 records · Page 6Linked to original sources

Urinary prostaglandin D synthase (beta-trace) excretion increases in the early stage of diabetes mellitus.

OBJECTIVE: Circulating levels of lipocalin-type prostaglandin D synthase (L-PGDS)/beta-trace reportedly increase in renal failure as well as in cardiovascular injuries. We investigated the alterations of L-PGDS in urine and plasma in the early stage of type-2 diabetic patients. METHOD: Thirty-six type-2 diabetic patients and 29 normal subjects were studied. Overnight spot urine and plasma samples were obtained in the morning. L-PGDS was measured by ELISA method using anti-L-PGDS antibody. Variables indicating renal function were determined. RESULTS: Plasma L-PGDS concentration was slightly higher in the patients with diabetes mellitus than in the control subjects, whereas the urinary L-PGDS excretion almost doubled in the diabetic patients as compared with that in the control subjects. Plasma L-PGDS was determined by plasma creatinine (Cr) concentration while urinary L-PGDS excretion was correlated solely with urinary protein excretion. There was no relationship between plasma L-PGDS concentration and urinary L-PGDS excretion. The averaged plasma concentration of L-PGDS in the diabetics with a normal Cr level in plasma, corresponding to that in the controls, was determined by the plasma Cr concentration. On the other hand, the urinary L-PGDS excretion was determined by the amount of proteinuria and greater in the diabetics with a normal Cr level in plasma than in the controls even when the patients exhibited urinary protein excretion equal to that in the control subjects. CONCLUSIONS: Urinary L-PGDS excretion increased in the early stage of kidney injury in patients with type-2 diabetes mellitus. The urinary excretion was correlated independently with urinary protein excretion even when there was no difference in urinary protein or albumin excretions, thereby suggesting that urinary L-PGDS excretion is possibly a more sensitive indicator of renal injuries than proteinuria. Urinary L-PGDS may thus predict the progression of renal injuries in diabetic patients.

Analysis of Variance↗

T cell vaccination eliminates antigen-specific T cells and prevents antigen-induced eosinophil recruitment into the tissue.

Asthma is characterized by airway inflammation with prominent eosinophil infiltrates. In a murine model of asthma, antigen-induced eosinophil recruitment into the airways of sensitized mice is mediated by CD4+ T cells and their cytokines, especially IL-5. In the present study, using ovalbumin-specific T cell receptor transgenic mice, we found that T cell vaccination, which was the administration of preactivated and attenuated antigen-specific T cells by the intraperitoneal route, prevented antigen-induced eosinophil recruitment into the airways. This effect was antigen-specific because ovalbumin-specific T cell vaccination did not affect BSA-induced eosinophil recruitment into the airways. We also found that antigen-specific IgE production as well as antigen-induced proliferation and cytokine production of splenocytes were diminished by T cell vaccination. Moreover, flow-cytometric analyses revealed that T cell vaccination eliminated antigen-specific T cells in the periphery. Together, these results indicate that T cell vaccination prevents antigen-induced eosinophil recruitment into the airways presumably by eliminating antigen-specific T cells.

Adoptive Transfer↗

Fas/FasL-dependent apoptosis of alveolar cells after lipopolysaccharide-induced lung injury in mice.

To determine the possible contribution of apoptosis in the pathogenesis of acute lung injury (ALI), we investigated Fas antigen (Fas), Fas ligand (FasL), perforin, granzyme A, and granzyme B expressions in a murine model of ALI after intratracheal instillation of Escherichia coli lipopolysaccharide (LPS: 0.3-30 microg) into the left lung. Lung injury, examined by water-to-dry weight ratio and albumin leakage, demonstrated maximal epithelial injury 1 d after 30 microg LPS instillation. Expressions of the proapoptosis molecules' mRNA were dose-dependently up-regulated, with maximal expression in the early phase in the instilled lung and most apparent 1 d after LPS instillation. Negligible mRNA expression of proapoptosis molecules was observed in noninstilled lungs. The terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) demonstrated positive signals in neutrophils and macrophages as well as in alveolar wall cells of the instilled lung 1 d after LPS instillation. Immunohistochemistry demonstrated that Fas was up-regulated in alveolar and inflammatory cells and FasL-positive inflammatory cells migrated into the air spaces in the LPS-instilled lung. Intratracheal administration of P2 antibody, which is an anti-Fas blocking antibody, attenuated the lung injury after 30 microg LPS instillation without attenuating mRNA expressions of proapoptosis molecules and neutrophil accumulation in the lung. In contrast, concanamycin A, which inhibits the function of perforin, did not alter the outcome after LPS instillation. These results indicate that the Fas/FasL system could be important in the pathogenesis of LPS-induced ALI, and proper regulation of the FasL/Fas system might be important for potential treatment of ARDS.

Animals↗

Short-term outcome of stent implantation in saphenous vein grafts: predictors of distal embolization and restenosis.

The present study, which aimed to determine the predictors of distal embolization and restenosis after stenting for vein graft disease, retrospectively analyzed 51 consecutive patients who underwent stent implantation for diseased saphenous vein grafts. Follow-up angiography was performed 6 months after the procedure and the clinical and angiographic variables were analyzed by multivariate logistic regression to determine the predictors of distal embolization and restenosis. Initial clinical success was achieved in 49 patients, 44 of whom underwent follow-up angiography and were enrolled in the retrospective analysis. Distal embolization occurred in 6 grafts (13.6%). Multivariate analysis showed that the lesion length and the total cholesterol level were independent predictors of distal embolization. Angiographic restenosis occurred in 13 (26.5%) of 49 lesions. The minimum luminal diameter and the percent diameter stenosis after stenting were associated with the occurrence of restenosis. Multivariate analysis of lesions located in the graft body identified graft age as an independent predictor of restenosis. Distal embolization can occur after vein graft stenting, especially in patients with hypercholesterolemia and diffuse stenosis. The post-stenting minimum luminal diameter and the percent diameter stenosis are predictors of restenosis. In particular, graft age is associated with the restenosis of graft body lesions.

Aged↗

[A pharmacological profile of clobazam (Mystan), a new antiepileptic drug].

Clobazam (CLB) is a new antiepileptic drug that is the first 1,5-benzodiazepine (BZP) having nitrogen atoms in the 1 and 5 positions of the heterocyclic ring, whose chemical structure was designed to give it a different pharmacological profile from that of 1,4-BZPs. Although CLB has a Ki value of 2,130 nM and thus has a lower affinity for the BZP receptor than 1,4-BZPs, it had the selectivity to omega 2 receptor contributing to anticonvulsive actions compared with omega 1 receptor in relation to other CNS activities such as sedation. CLB had a wide spectrum of anticonvulsive actions against seizures in several animal models induced by chemical convulsants and maximal electroshock. CLB reduced both seizure stage and afterdischarge duration in a dose-dependent manner in amygdala or hippocampal kindled rats. Usefulness of an anticonvulsant is generally assessed by quoting the protective index (PI) in the ratio of TD50 to ED50. As the PI for CLB was greater than that for 1,4-BZPs, it suggested that CLB was superior to 1,4-BZPs in tolerability while showing anticonvulsive actions. In clinical studies, CLB was used as an adjunctive treatment in patients with refractory epilepsies. From both experimental and clinical observations, CLB was proven to possess a wide spectrum of activity, high effectiveness and good tolerability in several types of epilepsies.

Animals↗

Suppressive effect of tranilast on interleukin-5 prolonged eosinophils survival via apoptosis.

Tranilast has long been used clinically to treat allergic diseases such as bronchial asthma. To further clarify the antiinflammatory machanism, we examined the ability of tranilast to counteract the prolongation of eosinophil survival induced by interleukin (IL)-5. Tranilast reduced the IL-5 prolonged survival of eosinophils at the concentration range of 30 microg/ml to 100 microg/ml. The DNA extracted from eosinophils cultured with tranilast showed signs of fragmentation that was comparable with apoptosis. Electron-microscopic analysis of activated eosinophils cultured with 100 microg/ml of tranilast also revealed morphologic features of apoptosis. These data suggest that tranilast may act in vivo on activated eosinophils to reduce inflammation in allergic diseases.

Anti-Allergic Agents↗

Cloning and characterization of the cpyA gene encoding intracellular carboxypeptidase from Aspergillus nidulans.

Carboxypeptidase Y (CPY) has been used as a maker enzyme for investigations on intracellular transport of vacuolar proteins and on vacuolar biogenesis in Saccharomyces cerevisiae. We describe the cloning and characterization of the CPY homologue encoding gene (cpyA) from the filamentous fungus Aspergillus nidulans. The cpyA gene has one intron and encodes a protein with 552 amino acids containing a putative signal sequence and pro-sequence. The predicted CpyA protein is highly similar in sequence with carboxypeptidases from several yeast species and contains a catalytic triad (Asp-His-Ser) like that of serine carboxypeptidase. The cpyA disruptant cells showed reduced levels of intracellular carboxypeptidase. These results suggest that the cpyA gene encodes a vacuolar carboxypeptidase in A. nidulans.

Amino Acid Sequence↗

Visualization of nuclei in Aspergillus oryzae with EGFP and analysis of the number of nuclei in each conidium by FACS.

Aspergillus oryzae has been reported to form conidia with multinuclei. In order to analyze nuclei in living cells, we developed an expression system of the A. nidutans histone H2B protein tagged by EGFP (H2B::EGFP). In both A. oryzae niaD300 and A. nidulans FGSC89 transformants expressing H2B::EGFP, fluorescence was detected in nuclear regions of hyphae and conidia. While a conidium contained only one fluorescent spot in the A. nidulans transformant, approximately 66% of conidia had two, 24% had one, and 10% had three or more in the A. oryzae transformant. The conidia expressing H2B::EGFP were put through FACS (fluorescence-activated cell sorting) analysis and two sharp peaks, corresponding to one and two nuclei in each conidium, were noted in the A. oryzae transformant. In addition, the A. oryzae uninucleate conidia that were successfully isolated by FACS reproduced conidia with almost the same number distribution of nuclei as that of the original. Conidia of five A. oryzae strains used in sake brewing were scored for the number of nuclei, showing that a varied number of nuclei existed in each conidium and some strains had a small number of uninucleate conidia.

Alcoholic Beverages↗

"Early" apoplexy due to traumatic intracranial aneurysm--case report.

A 76-year-old man presented with a traumatic aneurysm of the left internal carotid artery which caused repeated subarachnoid hemorrhages within 20 hours of a fall from a height. Early computed tomography (CT) detected no brain abnormalities, but repeat CT found subarachnoid hemorrhage. Internal carotid angiography detected a pseudoaneurysm, which was not treated because of his poor clinical condition. He died of multiple organ failure. Early detection of a traumatic intracranial aneurysm is important for the prevention of aneurysmal rupture, or "delayed" apoplexy. Review of 171 cases with traumatic aneurysms from the literature found that false negative angiography occurred only in three cases on post-trauma day 7 and thereafter. Early diagnostic angiography within a week of the initial trauma is indicated if traumatic aneurysm is suspected to detect early signs of irregularity, spasm, and narrowing of the arterial wall. Repeat angiography is indicated if aneurysmal formation is still highly suspected in spite of negative initial angiography.

Acute Disease↗

High incidence of arterial dissection associated with left vertebral artery of aortic origin.

The incidences of arterial dissection of the vertebral artery (VA) of aortic origin and VA of subclavian artery origin were determined. The origins of the left and right VAs were confirmed by angiography in 860 and 717 patients, respectively. Left VA of aortic origin was found in 21 patients (6 females and 15 males) but no right VA of aortic origin was found. Left VA of left subclavian artery origin was found in 837 patients and right VA of right subclavian artery origin in 717 patients. Arterial dissection of the VA occurred in 17 patients (6 females and 11 males), four patients with left VA of aortic origin, seven with left VA of left subclavian artery origin, four with right VA of right subclavian artery origin, and two with bilateral VAs of subclavian artery origin. Left VA of aortic origin (4 of 21 patients) was associated with a significantly higher incidence of VA dissection than left VA of left subclavian artery origin and right VA of right subclavian artery origin (p < 0.001). Left VA of aortic origin is associated with a predilection for VA dissection in comparison to VA of subclavian artery origin.

Aortic Dissection↗

Hemifacial spasm due to cerebellopontine angle meningiomas--two case reports.

A 54-year-old female and a 49-year-old female presented with complaints of hemifacial spasm. Both patients underwent surgery to remove cerebellopontine angle meningiomas. In one case, no vascular compression was observed at the root exit zone. The tumor was removed subtotally leaving residual tumor adhered to the lower cranial nerves. The hemifacial spasm disappeared immediately after the operation. The residual tumor was treated using gamma knife radiosurgery. In the other case, the root exit zone of the facial nerve was compressed by both the tumor and anterior inferior cerebellar artery and the tumor was removed totally. Postoperatively, the hemifacial spasm disappeared, but the patient suffered facial nerve paresis and deafness that was probably due to intraoperative manipulation. However, the facial nerve paresis gradually improved. Cerebellopontine angle meningioma with hemifacial spasm must be treated by surgical resection limited to preserve cranial nerve function. Subtotal removal with subsequent radiosurgery to treat the remaining tumor tissue is one option for the treatment of cerebellopontine angle meningioma.

Cerebellar Neoplasms↗

Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena in type 1 diabetes: close correlation between serological markers and histological evidence of cellular autoimmunity.

To better understand the pathogenesis of type 1 diabetes, we have developed pancreatic biopsy under laparoscope for recent-onset type 1 diabetic patients. The patients included 29 acute-onset type 1 diabetic patients, 5 latent-onset type 1 diabetic patients, and 1 type 2 diabetic patient. Their median age was 28 years, and the duration of diabetes at the time of biopsy was approximately 3 months. In 31 of 35 patients, we could obtain the pancreas tissue by punching. No serious complications, such as heavy bleeding, peritonitis, or pancreatitis, have been experienced. Pneumoderma was observed in two patients, and abdominal dull pain had continued for 2 days in two patients. However, special treatment was not necessary for these complications. T-cell-predominant infiltration to islets (insulitis) and hyperexpression of major histocompatibility complex class I antigens on islet cells were the two major findings and were observed in 17 of 29 recent-onset type 1 diabetic patients. These findings could be regarded as evidence of immune attack against beta-cells, and their presence was closely correlated with the presence of either anti-GAD or anti-IA-2 antibodies (P = 0.02). In conclusion, pancreatic biopsy under laparoscope is a safe procedure without serious complications, according to our findings, for detecting in situ autoimmune phenomenon in recent-onset type 1 diabetic patients.

Adolescent↗

Nitrobenzylthioinosine (NBT), a nucleoside transport inhibitor, protects against Shiga toxin cytotoxicity in human microvascular endothelial cells.

Infections with Shiga toxin (Stx)-producing Escherichia coli (STEC) cause microvascular endothelial cell damage, resulting in hemorrhagic colitis and hemolytic uremic syndrome. The prevention of endothelial cell damage is therefore a crucial step in overcoming this disorder. Here, we report that nitrobenzylthioinosine (NBT), a nucleoside transport inhibitor, has a protective effect against the cytotoxicity of Stxs in human microvascular endothelial cells (HMVECs). The relative viability of cells treated with 1.5-15 pM of Stx1 was reduced to 10-20% of that without Stx1. However, the viability of cells treated with NBT (10-100 microM) remained higher than 80%, even in the presence of Stx1. NBT also protected against Stx1 cytotoxicity in sodium butyrate-treated hypersensitive HMVECs. The protective effect of NBT against Stx cytotoxicity may be due to the depletion of ATP in the cells, thereby inhibiting the entry of Stx1.

Adenosine Triphosphate↗

Microstructure and corrosion behavior of binary titanium alloys with beta-stabilizing elements.

Binary titanium alloys with the beta-stabilizing elements of Co, Cr, Cu, Fe, Mn and Pd (up to 30%) and Ag (up to 45%) were examined through metallographic observation and X-ray diffractometry to determine whether beta phases that are advantageous for dental use could be retained. Corrosion behavior was also investigated electrochemically and discussed thermodynamically. Some cast alloys with Co, Cr, Fe, Mn, and Pd retained the beta phase, whereas those with Ag and Cu had no beta phase. In some alloys, an intermetallic compound formed, based on information from the phase diagram. The corrosion resistance deteriorated in the TiAg alloys because Ti2Ag and/or TiAg intermetallic compounds preferentially dissolved in 0.9% NaCl solution. On the other hand, the remaining titanium alloys became easily passive and revealed good corrosion resistance similar to pure titanium since their matrices seemed to thermodynamically form titanium oxides as did pure titanium.

Analysis of Variance↗

Serum prostaglandin D synthase level after coronary angioplasty may predict occurrence of restenosis.

Lipocalin-type prostaglandin D synthase (L-PGDS), which is responsible for the biosynthesis of PGD2, has recently been found to be present in the atherosclerotic plaque of the human coronary artery and also to be secreted in human serum. We measured the serum L-PGDS level and compared it with the expressions of the platelet membrane surface glycoprotein and neutrophil adhesion molecule in patients undergoing PTCA. The L-PGDS level significantly decreased (P < 0.01) and the platelet surface expression of CD62P (P-selectin) significantly increased (P < 0.01) immediately after PTCA in the coronary sinus blood. Both changes were inversely correlated (R = -0.72, P < 0.001). Although the L-PGDS level in the coronary sinus blood remained equivalent to the baseline level in patients who experienced restenosis, the level increased over the baseline level (P < 0.01) at 48 h after PTCA in patients without restenosis. Neutrophil surface expression of CD11b (alpha subunit of Mac-1) significantly increased at 24 h (P < 0.01) to 48 h (P < 0.001) after PTCA in the coronary sinus blood in patients with restenosis but the change showed less significant in patients without restenosis. The changes in the L-PGDS level and the CD11b expression at 48 h after PTCA were inversely correlated (R = -0.55, P < 0.05). An increased serum L-PGDS level at 48 h after PTCA possibly predicts the avoidance of late restenosis. It is suggested that reduction in PGD2 synthesis triggers platelet activation and that a subsequent increase in the PGD2 synthesis suppresses inflammatory reaction at the intervention site indicated by neutrophil activation and inhibits development of restenosis. Pharmacological or biological intervention that increases endogenous PGD2 synthesis should be tested as a new strategy to prevent restenosis.

Analysis of Variance↗

[Anesthesia for emergency surgery in a patient with Shy-Drager syndrome].

A 53-year-old man with Shy-Drager syndrome underwent emergency surgery for the resection of the larynx under general anesthesia. Anesthesia was induced with fentanyl 0.1 mg and thiopental 100 mg, and endotracheal intubation was facilitated with vecuronium 8 mg. The onset of action of vecuronium was very slow. Anesthesia was maintained with about 1% of sevoflurane, with nitrous oxide 3 l.min-1 in oxygen 3 l.min-1. Norepinephrine was effective for hypotension while dopamine was not. He was extubated on the first postoperative day without any complications. The effects of vecuronium, norepinephrine, and dopamine might be changed in the patient with Shy-Drager syndrome.

Anesthesia, General↗