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Biomedical subjects

H Hattori

Publications and source records attributed to H Hattori.

At least 19 recordsLinked to original sources

Tissue engineering of the intervertebral disc with cultured annulus fibrosus cells using atelocollagen honeycomb-shaped scaffold with a membrane seal (ACHMS scaffold).

The objective of the study was to investigate the regeneration of intervertebral discs after laser discectomy using tissue engineering procedures. Annulus fibrosus (AF) cells from the intervertebral discs of Japanese white rabbits were cultured in an atelocollagen honeycomb-shaped scaffold with a membrane seal (ACHMS scaffold), to produce a high-density, three-dimensional culture for up to 3 weeks. Although the DNA content in the scaffold increased at a lower rate than that in the monolayer culture, expression of type II collagen and glycosaminoglycan accumulation in the scaffold were at higher levels than in the monolayer. The AF cells that had been cultured in the scaffold for 7 days were allografted into the lacunae of intervertebral discs of recipients (40 rabbits, 14-16 weeks old; average weight, 3.2 kg), whose nucleus pulposus (NP) had been vaporised with an ICG dye-enhanced laser. The allografted cultured AF cells survived and produced hyaline-like cartilage. Furthermore, the narrowing of the intervertebral disc space of the cell-containing scaffold insertion groups was significantly inhibited after 12 post-operative weeks.

Animals↗

Activation of caspase-12 by endoplasmic reticulum stress induced by transient middle cerebral artery occlusion in mice.

We sought to clarify the involvement of caspase-12, a representative molecule related to endoplasmic reticulum (ER) stress-induced cell-death signaling pathways, in neuronal death resulting from ischemia/reperfusion in mice. Transient focal cerebral ischemia (1 h) was produced by intraluminal occlusion of the middle cerebral artery (MCA). We assessed the expression patterns of caspase-12, Bip/GRP78, an ER-resident molecular chaperone whose expression serves as a good marker of ER stress, and caspase-7 by Western blotting and/or immunohistochemistry. Double-fluorescent staining of caspase-12 immunohistochemistry and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) method was performed to clarify the involvement of caspase-12 in cell death. We confirmed that ER stress was induced during reperfusion in our model, as witnessed by up-regulated Bip/GRP78 expression in the MCA territory. Western blot analysis revealed that caspase-12 activation occurred at 5-23 h of reperfusion, and immunoreactivity for caspase-12 was enhanced mainly in striatal neurons on the ischemic side at the same time points. We found the co-localization of caspase-12 immunoreactivity and DNA fragmentation detectable by the TUNEL method. We did not detect the presence of caspase-7 in the ER fraction at the period of caspase-12 cleavage. Our results imply that cerebral ischemia/reperfusion induces ER stress and that caspase-12 activation concurred with ER stress. Caspase-12 seems to be involved in neuronal death induced by ischemia/reperfusion. Caspase-7 is not likely to contribute to the cleavage of caspase-12 in our experimental model.

Animals↗

Effect of milrinone on vecuronium-induced neuromuscular block.

We examined the effect of milrinone, a phosphodiesterase III inhibitor, on neuromuscular block induced by vecuronium. Thirty adult patients were randomly assigned to one of two equal groups: the milrinone group and the control group. Subjects in the milrinone group received an intravenous loading dose of milrinone 5 microg x kg-1x min-1 for 10 min, followed by an infusion at a rate of 0.5 microg x kg-1x min-1. Subjects in the control group received normal saline at a rate of 0.1 ml x kg-1 x h-1. Thirty minutes after the beginning of the infusion of milrinone, anaesthesia was induced with intravenous thiopental 4 mg x kg-1 and fentanyl 2 microg x kg-1, and was maintained with isoflurane in oxygen and nitrous oxide. Neuromuscular blockade was monitored electromyographically at the adductor pollicis muscle. The times from the administration of vecuronium 0.1 mg.kg-1 to the onset of neuromuscular block and the return of the first, second, third, and fourth response of the train-of-four were compared between the two groups. Times to the recovery of the ratio of the first twitch to the control twitch to 25%, 50% and 75%, and times to the recovery of train-of-four ratio to 25%, 50% and 75% were also compared between the two groups. The onset of neuromuscular block in the milrinone group was significantly slower than in the control group. The times to the returns of the four twitches of the train-of-four, times to recovery of the ratio of the first twitch to the control twitch to 25% and 50%, and the times to the recovery of the train-of-four ratio to 25% and 50% were significantly shorter in the milrinone group than in the control group. We conclude that milrinone delays the onset of neuromuscular blockade but hastens its recovery in anaesthetised patients receiving vecuronium.

Adult↗

Nodular sclerotic change in dermatofibrosarcoma protuberans: a potential diagnostic problem.

Nodular sclerotic change in dermatofibrosarcoma protuberans (DFSP) is not a well-recognized event. Sclerotic change is reported in three patients with DFSP: a 33-year-old woman with a left subclavian mass, a 29-year-old woman with a mass on the left crus and a 31-year-old man with a mass on the left cheek. Histologically, lesions consisted of two types of feature, one type being typical of DFSP and the other being rich in collagen. In the first patient, each type formed a distinct compartment, each of which contained scattered cells containing melanin pigment. In the second patient, foci with typical DFSP histology were distributed within the collagen-rich area and also formed a substantial compartment in the periphery of the lesion, with pigmented cells being distributed mainly in and around the cellular area. In the third patient, the collagenous area occupied about half of the lesion. There was no pigmentation. In all three cases the collagen-rich area contained sparsely distributed fibroblast-like cells that stained positive with CD34. Sclerotic change in DFSP could cause substantial difficulty in diagnosis if the biopsy material were partial and small. The clinical history and knowledge about the existence of this kind of histological variation in DFSP are important.

Adult↗

Th1 and Th1-inducing cytokines in Salmonella infection.

Thl and Thl-inducing cytokines and T cell responses were investigated in human salmonellosis. Serum IFN-gamma, IL-12 and IL-18 levels were increased significantly in patients with salmonellosis. The increase in serum IL-15 and IL-18 levels was more significant and prolonged in patients with the systemic form of salmonellosis than in those with the gastroenteric form. The serum IFN-gamma level was correlated significantly with IL-12 and IL18 levels, and the IL-15 level was correlated significantly with IL-18. Upon stimulation with Salmonella in vitro, mononuclear cells from salmonellosis patients produced significantly higher amounts of IFN-gamma and IL-12 compared with those from healthy controls. Anti-IL-12 moAb or anti-IL18 MoAb significantly inhibited Salmonella-induced IFN-gamma production in vitro. gamma delta T cells expressed significantly higher levels of IFN-gamma mRNA in salmonellosis patients than in healthy controls. The results suggest that Th1-inducing cytokines appear to be involved in the in vivo response against Salmonella infection, promoting IFN-gamma production by alpha beta and gamma delta T cells which plays a protective role against Salmonella.

Adolescent↗

Monitoring of neuromuscular block after administration of vecuronium in patients with diabetes mellitus.

BACKGROUND: We studied the supramaximal current for ulnar nerve stimulation during electromyographic monitoring of onset and recovery of neuromuscular block using a neuromuscular transmission module (M-NMT Module, Datex-Ohmeda) in patients with Type 2 diabetes undergoing anaesthesia with nitrous oxide, oxygen, isoflurane and fentanyl. METHODS: Thirty-six diabetic patients were randomly assigned to a post-tetanic count (PTC) group (n=17) or train-of-four (TOF) group (n=19). In addition, 30 non-diabetic patients were divided into control PTC (n=15) and TOF groups (n=15). RESULTS: In the diabetic patients (diabetes PTC and diabetes TOF groups), the mean supramaximal stimulating current was significantly higher than in the non-diabetic patients (control PTC and TOF groups) (50.5 (SD 14.1) vs 33.4 (6.1) mA, P<0.01). Onset of neuromuscular block (time to disappearance of T1) after vecuronium 0.1 mg kg(-1) in the diabetic patients did not differ significantly from that in the non-diabetic patients (276 (77) vs 244 (44) s, P=0.055). Time to return of PTC1 did not differ significantly between the diabetes and control PTC groups (21.0 (12.1) vs 15.7 (5.0) min, P=0.126). Times to return of T1 and T4 in the diabetes TOF group were significantly longer than in the control TOF group (T1: 37.5 (15.2) vs 25.7 (7.6) min, P=0.01; T4: 61.4 (23.7) vs 43.5 (11.4) min, P=0.01). During recovery, PTC and T4/T1 in the diabetes PTC and TOF groups were similar to those in the control PTC and TOF groups, respectively. T1/T0 in the diabetes TOF group was significantly less than in the control TOF group, 80-120 min after vecuronium (P<0.05). CONCLUSIONS: In diabetic patients, supramaximal current is higher than in non-diabetic patients. After vecuronium, onset of neuromuscular block and recovery of PTC or T4/T1 are not altered, but time to return of T1 or T4, and recovery of T1/T0 are delayed in diabetic patients.

Adult↗

Low-dose ACTH therapy for West syndrome: initial effects and long-term outcome.

BACKGROUND: Most Japanese pediatric neurologists attempt other treatments before using adrenocorticotropic hormone (ACTH) therapy for West syndrome (WS), and even then, they use only a low-dose synthetic ACTH to avoid serious adverse effects. In this multi-institutional study, the authors analyzed the initial effects, adverse effects, and long-term outcome in patients treated with low-dose synthetic ACTH in Japan. METHODS: The medical records of 138 patients with WS, who were treated with low-dose synthetic ACTH therapy for the first time at the authors' institutions between 1989 and 1998, were analyzed. RESULTS: At the end of ACTH therapy, excellent effect on seizures was noted in 106 of 138 (76%) patients, good effect in 23 (17%), and poor effect in 9 (7%). Initial effects on EEG were excellent in 53 of 138 (38%) patients, good in 76 (55%), and poor in 9 (7%). As for seizure prognosis at the time of follow-up, 51 of 99 (52%) patients were seizure-free, whereas 48 (48%) patients had seizures. Mental outcome was normal in 6 of 98 (6%) patients, mild mental retardation in 16 (16%), moderate mental retardation in 26 (27%), and severe mental retardation in 50 (51%). The initial effects of ACTH on seizures and long-term outcome were not dose dependent (daily dosage 0.005 to 0.032 mg/kg, 0.2 to 1.28 IU/kg; total dosage 0.1 to 0.87 mg/kg, 4 to 34.8 IU/kg). The severity of adverse effects correlated with total dosage of ACTH, and the severity of brain volume loss due to ACTH correlated well with the daily dosage and total dosage of ACTH. CONCLUSION: Low-dose synthetic ACTH therapy is as effective for the treatment of WS as the higher doses used in previous studies. The dosage of synthetic ACTH used in the treatment of WS can be decreased as much as possible to avoid serious adverse effects.

Brain↗

Polymorphisms of transforming growth factor-beta1 and transforming growth factor-beta1 type II receptor genes are associated with acute graft-versus-host disease in children with HLA-matched sibling bone marrow transplantation.

The aim of this study was to determine whether the gene polymorphisms of Th1/Th2 and immunoregulatory cytokines were associated with aGVHD in Japanese children receiving allogeneic bone marrow transplantation (allo BMT). We investigated polymorphisms of genes encoding interleukin (IL)-4, IL-4 receptor (IL-4 R), IL-10, transforming growth factor (TGF)-beta1, TGF-beta1 type II receptor (TGF-beta1 RII), interferon (IFN)-gamma, IFN-gamma type 2 receptor (IFN-gamma R2), and IFN regulatory factor (IRF)-1. Sixty-seven patients were treated with allo BMT from HLA-identical siblings, and aGVHD was observed in 38. TGF-beta1 codon 10 leucine (Leu) /proline (Pro) polymorphism in donors was associated with the development of aGVHD. Patients having donors with the Pro allele had aGVHD more frequently than those without Pro allele (30/45 vs 8/20, odds ratio = 3.00; P = 0.04). TGF-beta1 RII 1167 C/T polymorphism in recipients was also associated with the development of aGVHD. The incidence was significantly higher in recipients with T allele than in those without T allele (21/27 vs 16/35, odds ratio = 4.16; P = 0.01). In conclusion, genetic backgrounds of TGF-beta1 and TGF-beta1 RII may be involved in the development of aGVHD in HLA-matched sibling BMT in Japanese children.

Acute Disease↗

Carbohydrates expressed on Aspergillus fumigatus induce in vivo allergic Th2-type response.

BACKGROUND: The mould Aspergillus fumigatus (Af) causes several forms of Th2-biased diseases such as Type I respiratory allergies. This mould contains abundant carbohydrates including glucan, chitin and galactomannan. However, little is known on whether these carbohydrates directly drive Th2 responses in vivo. OBJECTIVE: We sought to determine the relative role of carbohydrates expressed on crude extracts of Af in the induction of Th2-type antibody production and local eosinophila in mice. METHODS: Carbohydrates on native Af were destroyed by sodium metaperiodate under mild conditions. CBA/J mice were sensitized intranasally with native, periodate-treated or mock-treated Af. Histologic changes and production of Af-specific IgE, IgG1 and IgG2a, as well as serum total IgE were determined. Inhibition ELISA for Af-specific IgE was performed using periodate-treated Af as an inhibitor. RESULTS: Mice sensitized with periodate-treated Af displayed significant decreases in both total and specific IgE levels in comparison to mice sensitized with native or mock-treated Af. Furthermore, sensitization and subsequent challenge with periodate-treated Af significantly reduced the degree of eosinophil recruitment into the nasal mucosa, compared to the controls. On the other hand, competitive inhibition showed that periodate-treated Af could inhibit binding between native Af and specific IgE in a similar manner to that of native and mock-treated Af. CONCLUSION: These results suggest that carbohydrates on Af play a key role as internal adjuvants in inducing the allergic Th2-type response and are not the targets of the induced IgE response.

Animals↗

Intranasal application of purified protein derivative suppresses the initiation but not the exacerbation of allergic rhinitis in mice.

BACKGROUND: Several epidemiological and experimental studies have demonstrated that exposure to pathogens such as those from the genus Mycobacterium leads to the suppression of allergic sensitization and inflammation. However, little is known as to whether pathogen-derived soluble antigens have the potential to modulate the pathogenesis of allergic rhinitis. OBJECTIVE: We sought to determine whether application of purified protein derivative (PPD) from Mycobacterium tuberculosis can suppress the initiation and/or exacerbation of allergic rhinitis using a recently developed murine model. METHODS: First, we investigated whether a single intranasal application of PPD could elicit cytokine production in the nose by RT-PCR. BALB/c mice were repeatedly sensitized with Schistosoma mansoni egg antigen (SEA) intranasally without an adjuvant. PPD was applied through different routes either before or after sensitization. The production of SEA-specific antibodies, nasal eosinophilia and cytokines by nasal lymphocytes was compared among mice that had or had not received PPD treatment. RESULTS: IFN-gamma, but not IL-4, was detected in the nasal tissue 12 to 48 h after a single intranasal application of 10 microg PPD. Repeated intranasal application of PPD prior to and during sensitization with SEA significantly inhibited the production of both SEA-specific IgE/IgG1 and nasal eosinophilia. Moreover, it partially inhibited the production of IL-4 by nasal lymphocytes in response to SEA. Conversely, this treatment led to a significant increase in IFN-gamma production. On the other hand, PPD applied through the footpad had no effect over the same period. Repeated intranasal application of PPD after sensitization with SEA had no exacerbative effect on allergic inflammation. CONCLUSION: These results indicate that the local application of PPD, and the subsequent induction of IFN-gamma, inhibits the initiation, but not the exacerbation, of allergic rhinitis in mice. This suggests that pathogen-derived antigens have potential for use in the prevention and prophylaxis of allergic rhinitis.

Administration, Intranasal↗

Sclerosing haemangioma of the lung is positive for MIB-1 in cell membrane and cytoplasmic staining pattern.

AIMS: MIB-1 is a monoclonal antibody raised against the recombinant part of the Ki67 antigen, which is expressed in the nuclei of all the active part of the cell cycle. Recently, cell membrane and cytoplasmic pattern of staining with MIB-1 in hyalinizing trabecular adenoma of the thyroid was reported. Sclerosing haemangioma of the lung is a tumour of uncertain histogenesis with a usually benign course. The tumour is mainly composed of cuboidal cells that line the papillary or tubular structure and pale cells that are found in the stroma. METHODS AND RESULTS: We examined a cell membrane and cytoplasmic immunoreactive pattern for MIB-1 antibody in sclerosing haemangioma. In all of the five cases examined, distinct cell membrane and cytoplasmic MIB-1 positivity mainly in the pale cells was noted. None of the carcinomas of the lung showed this type of staining with MIB-1. CONCLUSION: This result shows that, although the staining may be a result of cross reaction, cell membrane and cytoplasmic MIB-1 positivity is unique in that it could distinguish sclerosing haemangioma from other malignant epithelial tumours of the lung.

Cell Membrane↗