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Biomedical subjects

H Hashimoto

Publications and source records attributed to H Hashimoto.

At least 361 records · Page 20Linked to original sources

Protection against concanavalin A-induced murine liver injury by the organic germanium compound, propagermanium.

Propagermanium (3-oxygermylpropionic acid polymer) is an organic germanium compound that activates the immune system. In this study, we investigated the action of propagermanium on T-cell-mediated murine hepatic injury induced by concanavalin A (Con A). Oral administration of propagermanium inhibited the development of liver injury about 10 h after ConA injection. Histological analysis demonstrated that propagermanium attenuated the extent of liver damage compared with controls, reducing infiltration by leucocytes, especially CD11b-positive cells. Infiltration by CD4-positive cells was not affected. Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma are crucial for the development of hepatitis in this model. Propagermanium treatment induced significant inhibition of subsequent TNF-alpha production about 10 h after Con A injection, without affecting IFN-gamma, interleukin (IL)-10, IL-4 and IL-12 production. This effect on TNF-production coincided with the inhibition of aminotransferase activity late in the progression of Con A-induced liver injury. These facts suggest that this compound affects the macrophages (Mphi) function in the liver sinusoid. Therefore, Mphi were cultured with liver sinusoidal endothelial cells (SEC) and the effect of propagermanium on TNF-alpha production in the presence of IFN-gamma was determined. TNF-alpha production was reduced significantly in the coculture of Mphi and SEC when Mphi was treated with propagermanium. These results might explain the mechanisms by which propagermanium inhibits Con-A-induced liver injury. That is, propagermanium improves hepatitis through mechanisms including the reduced production of TNF-alpha, without modification of Th1- and Th2-cell function.

Animals↗

Left heart bypass using the oscillated blood flow with totally implantable vibrating flow pump.

Aiming at a totally implantable ventricular assist device (VAD), a vibrating flow pump (VFP) was developed in Tohoku University. A transcutaneous energy transmission system (TETS) using an amorphous fiber was developed for the totally implantable VAD system. The VFP works with a higher frequency than the natural heart of a biological system, a frequency of 10-50 Hz. In this research, animal experiments on left heart bypass were performed with healthy goats. Blood from the apex of the left ventricle was received and was sent to the aorta so that an adequate supporting effect of the left heart was provided. In particular, the depression effect of the left ventricle was obvious. As a result, sufficient artificial heart flow was provided. For a totally implantable type VAD, left heart bypass of almost 100% may become necessary in some situations. Therefore, apex approaches of left heart bypass may be desirable. From an anatomical consideration, an apex of the heart is suitable for the VFP of this totally implantable type. In the left heart bypass for which the apex of the heart was used, an almost 100% bypass was possible. This is a requirement that is important when waiting for recovery of sufficient cardiac function. It is also important that left heart circulation is maintained fully by an artificial heart of the complete implantation type. The VFP was considered to be useful as a totally implantable type artificial heart from the results.

Animals↗

Control of the pulmonary arterial resistance by the use of the oscillated assist flow.

In the clinical application of supporting circulation, the treatment of a patient with pulmonary hypertension is very important. We developed the electromagnetically driven vibrating flow pump (VFP) as a totally implantable type ventricular assist system. The artificial heart driven by electromagnetic forces creates high speed oscillation flow around 10-50 Hz. Assistance by high-speed oscillation flow has an interesting influence on the cardiovascular system. In this study, we carried out research on the influence such oscillation flow had on the pulmonary arterial vessels, and the supporting flow wave-form that controlled pulmonary vascular resistance was considered. Six healthy adult goats of both sexes were used in the experiments. We carried out inhalation anesthesia and performed intubation. The thorax was opened through left fourth rib resection. Right heart bypass was performed from the right atrium to the pulmonary artery. The flow of right heart assistance was maintained within 20-25% of total flow. Our purpose was to add flow of a specific high frequency to the right heart circulation. The hemodynamic parameters were recorded on a magnetic tape data recorder and input into a computer through an A-D converter. A result identified was that the pulmonary vascular resistance changed according to the alteration of the driving frequency of the VFP even during the same flow assistance. The resistance of the pulmonary arterial vessels became smaller when the driving of the VFP of 30 Hz was added to the right heart circulation. This was significant even when compared with continuous flow right heart assist. The characteristics of impedance appeared to have interesting alterations as well. Control of pulmonary vascular resistance by right heart assistance becomes possible if these results are applied. Accordingly, it may become one of the choices for treatment of a patient with pulmonary hypertension.

Animals↗

The effect of lesionectomy and the perilesional GABAergic neuronal changes in alumina cream-induced focal motor epilepsy in cats.

The effect of lesionectomy depends on the reversibility of the epileptogenic changes in the perilesional cortex. We studied how the perilesional GABAergic neuronal changes are related to the effect of lesionectomy in the alumina cream-induced focal epilepsy model in cats. Sequential changes of GABAergic neurons and spike activities were measured after the micro-injections of alumina cream (AC). Alumina granulomas were excised 15 days and 40 days after the injections. At day 20 following the AC injection, GABAergic neurons were decreased 25 to 40% compared with those in the contralateral intact cortex. At day 40, a significant increase of spike activities occurred. GABA positive cells were decreased more than 50% compared with those in the contralateral cortex. At day 80, significant cell loss in perilesional cortex was demonstrated. The effect of lesionectomy was greater in the early excised group than in the late excised group. Decrease of GABAergic neuron was more severe in the late excised group compared to the early excised group. Our results indicate that more than 50% reduction of perilesional GABA neurons may be a critical point in epileptogenesis in this model. Lesionectomy alone prior to a 50% reduction in perilesional GABAergic neurons may be sufficient for seizure control. With these data it is still unclear whether these findings contribute to the choice between lesionectomy alone and lesionectomy with resection of the perilesional cortex. Further study is needed to understand the difference between the AC epilepsy model and human chronic epilepsy.

Aluminum Oxide↗

Existence of two isoforms of extracellular signal-regulated kinase in fish.

Full-length cDNAs for extracellular signal-regulated kinases (ERK1 and ERK2) were isolated from a carp ovary cDNA library. The deduced amino acid sequences of carp ERK1 (cERK1) and ERK2 (cERK2) exhibited high degrees of homology to the known sequences of the ERK group. Northern blot analysis showed that cERK1 mRNA was not expressed in a tissue-specific manner, though the level of expression of cERK2 mRNA varied among tissues. Western blot analysis of the brain, kidney, and ovary confirmed the expression of cERK1 and cERK2 in carp. Our findings indicate that two isoforms of ERK, ERK1 and ERK2, exist in fish.

Amino Acid Sequence↗

Circulating interleukin-16 in systemic lupus erythematosus.

OBJECTIVE: To investigate the relationship between interleukin (IL)-16 and systemic lupus erythematosus (SLE). METHODS: Serum levels of IL-16 were examined in SLE patients using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum level of IL-16 in the patients was much higher than that in healthy volunteers (P < 0.001). An increase in IL-16 was observed in proportion to the activity of SLE assessed by the SLE Disease Activity Index (SLEDAI) score (P < 0.0001). CONCLUSIONS: Our observations suggest an interaction between disease activity and the production of IL-16 in SLE, and reveal that IL-16 is a useful indicator of disease activity. This is the first report describing the relationship between IL-16 and SLE.

Adolescent↗

Intraoperative modulation of alveolar macrophage function during isoflurane and propofol anesthesia.

BACKGROUND: Alveolar macrophages are a critical part of the defense against pulmonary infection. Thus the authors determined time-dependent changes in alveolar macrophage functions in patients having surgery who were anesthetized with isoflurane or propofol. METHODS: Patients anesthetized with propofol (n = 30) or isoflurane (n = 30) during orthopedic surgery were studied. Alveolar macrophages were harvested by bronchoalveolar lavage immediately, and 2, 4, and 6 h after induction anesthesia and at the end of surgery. The fraction of aggregated and nonviable macrophages was determined. Then phagocytosis was measured by ingestion of opsonized and unopsonized particles. Finally, microbicidal activity was determined as the ability of the macrophages to kill Listeria monocytogenes directly. RESULTS: Demographic and morphometric characteristics of the patients given propofol and isoflurane were similar, as were their levels of pulmonary function and hemodynamic responses. The fraction of alveolar macrophages ingesting opsonized and unopsonized particles, and the number of particles ingested, decreased significantly over time, with the decrease slightly but significantly greater during isoflurane anesthesia. Microbicidal function decreased progressively during anesthesia and surgery, with the decrease almost twice as great during isoflurane compared with propofol anesthesia. The fraction of aggregated macrophages and recovered neutrophils increased over time in the patients given each anesthetic. CONCLUSIONS: Pulmonary immunologic function changed progressively during anesthesia and surgery. The data from this study suggest that pulmonary defenses are modulated by the type of anesthesia and by the duration of anesthesia and surgery.

Adult↗

Reversible ischemia in hippocampal areas by retrograde cerebral circulation surgery for thoracic aortic aneurysm with Tc-99m ECD brain SPECT.

Because hippocampal neurons are quite vulnerable to the anoxic brain injury that sometimes occurs in aortic arch surgery in humans, hippocampal ischemia should be a sensitive indicator of global cerebral ischemia. It was concluded that the hypothermic retrograde cerebral circulation technique for aortic arch surgery could not only be performed safely with respect to the brain, but could also increase blood flow to the hippocampal areas, probably as a result of restoration of blood flow in the thoracic aorta.

Adult↗

Relationship between recurrence of gastric ulcer and the microcirculation.

We investigated the relationship between microcirculatory disturbance and the host response to Helicobacter pylori infections in gastric ulcer scars to determine the role of endothelin-1 (ET) in ulcer recurrence. The subjects were divided into three groups. The GuS group consisted of patients who had red scarring (S1 stage) at the gastric angle with H. pylori, the gast+ group who had gastritis with H. pylori, and the gast- group who had gastritis without H. pylori. During endoscopic examination, biopsies were taken from the gastric angle. Mucosal ET, nitric oxide (NO), interleukin-8 (IL-8), and RANTES were measured. ET, inducible NO synthase (iNOS), and endothelial constitutive NOS (ecNOS) were immunostained. Mucosal ET and oxides of nitrogen (NOx) were significantly higher in the GuS group than in the other groups. IL-8 was elevated in the GuS and gast+ groups, and RANTES was elevated in the gast+ group (p < 0.01). There was prominent inflammatory cell infiltration in the GuS group. ET-positive cells were found in vascular smooth muscle, gastric epithelium, and gastric smooth muscle. iNOS-positive cells were found in vascular smooth muscle, gastric epithelium, gastric smooth muscle, and inflammatory cells. In conclusion, local inflammation and microcirculatory disturbance persist at the center of the ulcer scar (S1). Decreased cytokine levels and increased ET and NO (mainly synthesized by iNOS) levels suggested that microcirculatory disturbance is a more important factor than immune response in ulcer recurrence.

Cytokines↗

Effects of astemizole on ventricular activation, effective refractory periods, RT intervals, and programmed stimulation-induced ventricular arrhythmias in dog hearts with myocardial infarction.

To clarify the mechanisms of enhanced cardiotoxic effects of astemizole in ischemic hearts, we examined the effects of astemizole on ventricular activation, effective refractory periods (ERPs), RT intervals, and incidence of programmed electrical stimulation (PES)-induced ventricular arrhythmias in the dog heart after myocardial infarction. Myocardial infarction was produced by the two-stage ligation of left anterior descending coronary artery in dogs. At 7 days after ligation, bipolar electrodes were sutured on the ventricular surface of the infarcted and the normal zones for applying an electrical stimulation or recording the ventricular activation. Ventricular-activation delay was measured in a premature excitation, which was produced by a stimulation at a coupling interval between 300 and 140 ms on the ventricular surface of the normal zone. The ERP and the RT interval were determined during atrial pacing. The ventricular-activation delay increased after astemizole at doses of 0.3-3 mg/kg in the infarcted zone and at 3 mg/kg in the normal zone. Astemizole at doses of 0.3-3 mg/kg significantly prolonged the ERP to a greater extent in the infarcted zone than in the normal zone, and thus a dispersion of ERP between normal and infarcted zones increased. The RT interval in the normal zone significantly increased after astemizole to a greater extent at a long coupling interval. The RT interval in the infarcted zone also increased after astemizole at doses of 0.1-3 mg/kg to a greater extent than that in the normal zone. Astemizole at doses of 0.3-3 mg/kg increased the incidence of PES-induced ventricular arrhythmias. In conclusion, enhanced cardiotoxic effects of astemizole in ischemic hearts may be caused by increased activation delay in the ischemic regions and increased ERP dispersion in the ventricle.

Animals↗

Detection of TLS/FUS-CHOP fusion transcripts in myxoid and round cell liposarcomas by nested reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues.

The reciprocal translocation t(12;16)(q13;p11) has been shown to be highly characteristic of myxoid and round cell subtypes of liposarcoma, and the TLS/FUS-CHOP fusion gene that resulted from the translocation is expected to be a diagnostic molecular marker of these sarcomas. In this study, we conducted a nested reverse transcription-polymerase chain reaction (RT-PCR)-based assay to detect the TLS/FUS-CHOP fusion gene transcripts using archival formalin-fixed, paraffin-embedded tumor specimens. Of 18 paraffin-embedded specimens from 16 myxoid and round cell liposarcoma cases, the fusion transcripts could be identified in 16 (89%) specimens from 15 (94%) cases. A sequence analysis using the PCR products confirmed that the detected messages were derived from either type I or type II TLS/FUS-CHOP fusion gene, the latter of which was predominant (80%). The results were consistent in primary and recurrent lesions of the same patients and in paraffin-embedded and snap-frozen samples from the same tumors. In two negative specimens, transcripts of the beta-actin gene could not be detected by RT-PCR, and intact mRNA including the fusion messages might have been degraded. No fusion transcripts were detected in snap-frozen or paraffin-embedded material of other types of tumors with myxoid morphology (seven myxoid malignant fibrous histiocytomas and four lipomas with myxoid change). These results indicate that this molecular assay can be applied to formalin-fixed, paraffin-embedded tumor tissues as a diagnostic aid for these subtypes of liposarcoma.

Adolescent↗

Outcome of collagen vascular diseases by treatment with plasmapheresis.

The outcome of collagen vascular diseases after treatment with plasmapheresis was studied in 9 patients with polyarteritis nodosa (PN), in 2 patients with Wegener's granulomatosis (WG), in 1 patient with allergic granulomatous angitis (AGA), and in 20 patients with systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome (APS). Improvement after treatment with plasmapheresis was observed in 41.7% of the patients with PN, WG, and AGA. On the other hand, with the exception of 1 patient with thrombocytopenia and 1 patient with renal failure, all of the clinical manifestations, including thrombocytopenia, central nervous system (CNS) lupus, thrombophlebitis, lung infarction, and recurrent abortions in the SLE patients with APS, improved after plasmapheresis. Plasmapheresis is thought to be an influential strategy of treatment for patients with collagen vascular diseases.

Adult↗

Presymptomatic brain lesions on MRI in a patient with intravascular malignant lymphomatosis.

A 58-year-old man with a intravascular malignant lymphomatosis initially developed myeloradiculopathy without cerebral symptoms. His MRI, however, demonstrated solid, wedge-shaped, and well-demarcated lesions in the deep white matter and a string-shaped lesion along with nerve fibers in the splenium of corpus callosum. A variety of cerebral symptoms manifested a month afterward. The possibility of this disease should be considered in cases of undiagnosed myeloradiculopathy with such silent brain lesions.

Brain↗

Involvement of simultaneous multiple transcription factor expression, including cAMP responsive element binding protein and OCT-1, for synovial cell outgrowth in patients with rheumatoid arthritis.

OBJECTIVE: To elucidate possible roles of several transcription factors in the pathogenesis of rheumatoid arthritis (RA), the transcription factor expression in RA synovial tissue and their contribution to RA synovial cell functions were studied. METHODS: Single cell suspension of dissociated synovial tissue was cultured to induce in vitro tissue outgrowth of RA synovial cells. Transcription factors were immunohistochemically identified in RA synovial tissue obtained by joint surgery and in the in vitro tissue outgrowth, and confirmed by western blotting and gel shift assays. RESULTS: Immunohistochemical examination of RA synovial tissue revealed simultaneous expression of various transcription factors (NF-kappa B, c-Jun (a component of AP-1), cAMP responsive element binding protein (CREB), and OCT-1). The same set of transcription factors was expressed in the in vitro tissue outgrowth of RA patients. The early passage RA synovial cells were treated with interleukin 1 beta (IL1 beta) and confirmed translocation of transcription factors into the nucleus by western blotting, and their DNA binding activity by gel shift assays. CONCLUSION: This study emphasises the importance of the simultaneous expression of several transcription factors for the hyperactivity of RA synovial cells that leads to tissue outgrowth.

Adult↗

Basal cell carcinoma within vulvar Paget's disease.

An 85-year-old Japanese woman had noticed erythema on her vulvar region 3 years before. The erythema gradually increased in size and followed erosion and ulceration with pigmentation on the edge of the erythema. A skin biopsy from the pigmented area showed large round cells with ample cytoplasm, which formed nests or glandular structures. In the dermis there was mass formation of basophilic cells and peripheral cells in a palisade arrangement. The tumor cells in the epidermis showed positive immunoreactivity for carcinoembryonic antigen; on the other hand, the dermal tumor was negative. We diagnosed that the tumor in the epidermis was vulvar Paget's disease, and the dermal tumor was a solid type of basal cell carcinoma. We speculate that the vulvar Paget's disease preceded and then the basal cell carcinoma developed in the area of Paget's disease. This is the first report in which basal cell carcinoma in the area of Paget's disease was documented.

Aged↗

Effect of extremely low dose cyclosporine treatment on the thrombocytopenia in systemic lupus erythematosus.

Cyclosporine is widely known to be effective in cases involving both transplantation as well as a spectrum of immune-mediated diseases, although careful monitoring is required for the preemptive detection of its adverse effects. Here we report the successful treatment by extremely low dose cyclosporine (1 mg/kg per day) of two patients with thrombocytopenia in systemic lupus erythematosus.

Adult↗