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Biomedical subjects

A Ogata

Publications and source records attributed to A Ogata.

At least 37 records · Page 2Linked to original sources

Endoscopic evaluation of centrally located early squamous cell carcinoma of the lung.

BACKGROUND: Lung-sparing treatment recently has become a choice in the treatment of patients with early hilar lung carcinoma. To select the method of treatment, it is important to evaluate the histologic extent of the tumor using endoscopy. METHODS: A total of 46 patients who underwent surgery for an endoscopically evaluated early lung carcinoma of the tracheobronchial tree were analyzed. Initial surgery was performed in 16 patients and in 30 patients surgery was performed after preoperative laser therapy. The endoscopic findings were classified into three types: superficial, nodular, and polypoid. In the resected lung, the greatest tumor dimension, the depth of mural invasion, the presence of microscopic blood and lymph vessel invasion, and metastases to the dissected lymph nodes were examined. RESULTS: The mean greatest tumor dimensions were 14.6 +/- 7.3 mm (mean +/- standard deviation) in the nodular group, 23.3 +/- 12.8 mm in the superficial group, and 19.0 +/- 9.2 mm in the polypoid group. The greatest tumor dimension in the superficial group was significantly larger than that in the nodular group (P < 0.01). Preoperative endoscopic diagnosis of early hilar lung carcinoma was correct histologically in 34 of 46 cases (74.0%). Hilar lymph node metastases (N1), extrabronchial invasion, and extension to the peripheral bronchus were recognized in 12 cases. Complete disappearance of the tumor due to preoperative laser therapy was confirmed in eight patients. Lymph node metastasis was not found when the greatest tumor dimension measured < 8 mm. The overall absolute 5-year survival rate was 76.0% for all patients, 87.1% for the surgery alone group, and 70.0% for the surgery after preoperative laser therapy group. CONCLUSIONS: Curative treatment of early hilar lung carcinoma is possible using photodynamic therapy alone when the tumor size is < or = 8 mm and the lesion does not extend to the peripheral bronchus.

Aged↗

Goitrogenic effects of green tea extract catechins by dietary administration in rats.

The effects of green tea extract catechins on the rat thyroid were examined in a 13-week feeding study and subsequent 2-,4- and 8-week studies. Commercially available polyphenon-60 (P-60) which contains green tea extract catechins at 66.2% was used as a source of catechins. A basic diet containing different concentrations of P-60 was used for experiments. In the 13-week study, 10 rats of each sex were administered diets containing P-60 at 0 (control), 0.625, 1.25, 2.5 and 5.0%. Goiters were observed in the 13-week test. The mean thyroid weight of rats fed a diet containing 5.0% of P-60 (5.0% group) significantly increased to 444% of the control in males and to 304% of the control in females. Histological examinations of the thyroid of the 5.0% group revealed marked hypertrophy and/or hyperplasia of the follicles, some with depletion of colloid and some with rich colloid, and formation of a fibrous capsule. Slight hypertrophy of follicular cells was observed in male rats fed a diet containing 1.25% of P-60 (1.25% group) and female rats fed a diet containing 2.5% of P-60 (2.5% group). Degree and incidence of thyroid lesions were higher in males than in females in the 1.25, 2.5 and 5.0% groups. In the 2-8-week studies, five rats of each sex were given diets containing 0 (control) and 5.0% of P-60. In the 5.0% group, the mean thyroid weight in males significantly increased to 161% of the control as early as 2 weeks and increased to 357% of the control at 8 weeks. Histologically, these goiters were also associated with follicular cell hypertrophy/hyperplasia as in the 13-week study. The degree and incidence of thyroid lesions were higher in males than in females. These results indicate that dietary administration of the green tea extract catechins at high doses induced goiters in rats, and this may be due to antithyroid effects of catechins. In the 13-week study, the no-observed effect level (NOEL) of green tea extract catechins for F344 rats based on histological changes of the thyroid was considered to be 0.625% in males and 1.25% in females in the diet, respectively.

Administration, Oral↗

Early hilar lung cancer--risk for multiple lung cancers and clinical outcome.

In early hilar lung cancer patients, multiple lung cancers frequently develop. The clinical outcome of such patients were studied. A total of 91 patients, 88 men and three women, who were endoscopically diagnosed with early hilar lung cancer were studied retrospectively. Surgery was performed in 46 patients, while organ-sparing treatment, including photodynamic therapy (PDT), Nd-YAG (neodymium-yttrium, argon, garnet) laser vaporization, and radiotherapy, were done for 45 patients. During follow-up, newly developed lung cancers and/or malignancies in other organs were recorded. The average smoking index (cigarettes per day x years) was 1040. Synchronous and/or metachronous multiple lung cancers developed in 26/91 patients (28.6%). Malignancies in other organs were found in 12/91 (13.2%). The smoking index of patients with multiple lung cancers was significantly higher than for other patients. The overall 5 year survival rate was 70.7% in all patients, 76.0% in the surgery group, and 64.4% in the nonsurgery group. The lung cancer-specific 5 year survival rate was 89.8% in all patients, 89.3% in the surgery group, and 90.5% in the nonsurgery group. Early hilar lung cancer frequently accompanies other lung cancers or malignancies in other organs. A favorable prognosis can be obtained with organ-sparing treatment.

Adult↗

The role of donor T cells for target organ injuries in acute and chronic graft-versus-host disease.

Donor T cells are crucial for target organ injury in graft-versus-host disease (GVHD). We examined the effects of donor T cells on the target organs using a parent-into-F1 model of acute and chronic GVHD. Donor T cells showed engraftment in the spleen, small intestine and liver of mice with acute GVHD, causing typical GVHD pathology in these organs. Interferon-gamma and Fas ligand expression were up-regulated, and host lymphocytes were depleted in the target organs of these mice. In contrast, donor T cells did not show engraftment in the small intestine of mice with chronic GVHD, and no GVHD pathology was observed in this organ. However, both donor T-cell engraftment and GVHD pathology were observed in the spleen and liver of chronic GVHD mice, along with the up-regulation of interleukin-4 (IL-4) and IL-10 expression plus the expansion of host lymphocytes such as splenic B cells and hepatic natural killer (NK) 1.1+ T cells. Donor anti-host cytotoxic T-lymphocyte activity was observed in spleen cells from mice with acute GVHD, but not in spleen cells from mice with chronic GVHD. Transplantation of Fas ligand-deficient (gld) spleen cells did not induce host lymphocyte depletion in target organs. These results indicate that donor T cells augment type 1 T helper immune responses and deplete the host lymphocytes from target organs mainly by Fas-mediated pathways in acute GVHD, while donor T cells augment type 2 T helper immune responses and expand host splenic B cells and hepatic NK1.1+ T cells in chronic GVHD.

Acute Disease↗

Reversible brain dysfunction in MELAS: MEG, and (1)H MRS analysis.

This case report describes a follow up investigation of a patient with impaired word discrimination due to mitochondrial encephalopathy with lactic acidosis and stroke-like syndrome (MELAS) using proton magnetic resonance spectroscopy ((1)H MRS) and auditory evoked magnetic fields (AEFs). The initial (1)H MRS showed no N-acetyl aspartate (NAA) and marked accumulation of lactate (Lac) in the stroke-like lesion of MELAS, which was silent in neural activity according to AEFs. The follow up investigations, however, demonstrated that NAA reappeared, that the formerly increased Lac signal was significantly reduced, and that the magnitude of AEFs of the lesion was markedly increased. Metabolic and functional changes in (1)H MRS and AEFs reflected the neurological recovery very well. The stroke-like lesion was shown, using AEFs and (1)H MRS, to be able to function properly, although brain tissue of the lesion initially had severe damage due to mitochondrial dysfunction.

Adult↗

[Analysis of 5-HT3 receptor antagonist, ramosetron hydrochloride, based on receptor occupancy considering its active metabolite].

Severe nausea and vomiting induced by antineoplastics diminish the patient's quality of life and the ability to tolerate further chemotherapy. Ramosetron hydrochloride is a 5-HT3 receptor antagonist, which has an active metabolite (M-1), expected to be useful in the inhibition of chemotherapy-induced nausea and vomiting. In the present study, in order to analyze the pharmacological effect of ramosetron hydrochloride in a comprehensive manner, we estimated the 5-HT3 receptor occupancy after intravenous administration of ramosetron hydrochloride using pharmacokinetic parameters and the dissociation constants for the 5-HT3 receptor. The average total receptor occupancy after intravenous administration of 0.3 mg of ramosetron hydrochloride to human was calculated to be 82.9% (ramosetron, 77.8%; M-1, 5.1%), thus exhibiting a significant antiemetic activity. Furthermore, the estimated time course of 5-HT3 receptor occupancies after intravenous administration of 0.3 mg of ramosetron hydrochloride suggested a substantial impact of the active metabolite (M-1). It suggested that M-1 contributed to the long duration of binding on the 5-HT3 receptor. The present analysis method should be useful for designing the rational dosage regimen of ramosetron hydrochloride and predicting the duration of its antiemetic activity in a quantitative manner.

Benzimidazoles↗

Changes of immunological response after experimentally ozonated autohemoadministration in calves.

Changes in subsets of peripheral blood mononuclear cells and lymphocyte blastogenesis reaction were observed after ozonated autohemoadministration (OAHA) in calves. Ten healthy calves were used in this study. After OAHA, CD8+ cells, CD14+ cells and WCl+cells increased (p<0.05). The level of lymphocyte blastogenesis stimulated by PHA decreased after OAHA. A significant increase in serum IL-6 activity was observed in OAHA calves. These results suggested that OAHA induced immunological changes in calves.

Animals↗

MR imaging of the brain in lymphomatoid granulomatosis.

BACKGROUND AND PURPOSE: Clinical diagnosis of lymphomatoid granulomatosis (LG) of the brain, in patients without skin or chest lesions, usually is difficult because of the nonspecific neurologic manifestations, laboratory data, and CT appearance. Our aim was to characterize the MR appearance of LG of the brain. METHODS: We retrospectively reviewed the MR images in four patients (35 to 72 years old) with histologically confirmed LG of the brain. RESULTS: On T2-weighted images, we noted diffuse hyperintense lesions in the cerebral white matter bilaterally (n = 3), in the brain stem and cerebellar hemisphere (n = 1), and patchy hyperintense lesions the brain stem (n = 2). On contrast-enhanced T1-weighted images, we observed multiple punctate or linear enhancements residing along the perivascular space (n = 4), nodular enhancements (n = 2), ringlike enhancements (n = 1), and a large, enhanced mass (n = 1). All patients had multifocal lesions. CONCLUSION: Although the MR appearance of LG of the brain varies, multiple punctate or linear enhancements that reside along the perivascular space suggest LG.

Adult↗

Macrophage migration inhibitory factor as a target molecule in multiple sclerosis.

Various therapeutic approaches to multiple sclerosis (MS) have been presented, but no specific and effective method has so far been established. In recent years, macrophage migration inhibitory factor (MIF) has been re-evaluated as a pluripotent cytokine involved in a broad spectrum of inflammation and immune responses. During the course of MIF study, increased levels of MIF were observed in the cerebrospinal fluids of patients with MS in parallel with exacerbation of clinical symptoms, and a number of lymphocytes strongly expressing MIF infiltrate into the pathogenic lesions. It is expected that regulation of the action of MIF by an anti-MIF antibody or small molecule inhibitors would be an effective therapeutic method for this demyelinating disease.

Animals↗

Japanese encephalitis virus up-regulates expression of macrophage migration inhibitory factor (MIF) mRNA in the mouse brain.

Macrophage migration inhibitory factor (MIF) is known as a proinflammatory cytokine, glucocorticoid-induced immunomodulator, and pituitary hormone, and contributes to broad-spectrum immune and inflammatory response. To investigate the expression of MIF in the central nervous system in an event of viral infection, we evaluated MIF mRNA expression in the mouse brain infected with Japanese encephalitis virus (JEV). In situ hybridization revealed that MIF mRNA expression was significantly up-regulated in the whole brain by intracranial JEV inoculation at 2 days post-inoculation (d.p.i.). Neurons as well as glial cells expressed MIF transcripts in which some of these cells were co-labeled by double staining for JEV antigens and MIF mRNA. At 4 d.p.i., when typical symptoms of encephalitis were observed, JEV antigen-positive cells were much increased in parallel with enhanced MIF mRNA, consistent with the results of Northern blot analysis. Reverse transcription-polymerase chain reaction showed that MIF mRNA was minimally changed at 1 d.p.i. in comparison with that at 0 d.p.i., but markedly up-regulated after 2 d.p.i. and sustained up to 4 d.p.i. On the other hand, a significant increase of tumor necrosis factor (TNF)-alpha mRNA was observed after only 3 d.p.i. These data suggest the possibility that MIF is involved in virus-induced encephalitis with regard to not only immune responses in the early stage, but also the exacerbation of inflammation in concert with TNF-alpha in the late stages. This is the first evidence demonstrating that MIF is up-regulated in the case of virus-induced encephalitis, which should contribute to the further understanding of the pathological mechanism of JEV-induced encephalitis.

Animals↗

Macrophage migration inhibitory factor in the cerebrospinal fluid of patients with conventional and optic-spinal forms of multiple sclerosis and neuro-Behçet's disease.

Macrophage migration inhibitory factor (MIF) is becoming increasingly recognized as an important regulator of immune and inflammatory responses. It is released by activated T lymphocytes and macrophages and up-regulates the proinflammatory activity of these cells. MIF is required for antigen- and mitogen-driven T cell activation, and stimulates macrophages to release cytokines and nitric oxide. On the basis of the recent suggestion that pharmacological modulation of MIF production and neutralization of its activity may have important implications for treatment of a variety of autoimmune or inflammatory conditions, we determined the level of MIF in the cerebrospinal fluid (CSF) of patients with conventional-form multiple sclerosis (C-MS) and optic-spinal form multiple sclerosis (OpS-MS), and neuro-Behçet's disease (NBD). As control, the CSF of patients with non-inflammatory neurological diseases (NIND) was used. The concentration of MIF in CSF samples was significantly elevated in relapsed cases of C-MS (4.13+/-1.07 ng/ml) (mean+/-S.D.) compared with control samples (2.38+/-0.60 ng/ml) (P<0.0001), whereas MIF in the CSF of C-MS patients in remission was not elevated (2.65+/-0.67 ng/ml). The concentration of MIF in the CSF of OpS-MS patients in relapse (5.53+/-1.74 ng/ml) was higher than that of patients with C-MS in relapse (P<0.05). In NBD patients, the concentration of MIF in CSF was significantly elevated (7.47+/-5.61 ng/ml) compared with control samples (P<0.01) and correlated well with cell count in these samples (r=0.910, P<0.005). These results suggest that MIF may play a pivotal role in immune-mediated diseases of the central nervous system, and that MIF may be useful in the study of differences between C-MS and OpS-MS.

Adolescent↗

Intracellular distribution of macrophage migration inhibitory factor predicts the prognosis of patients with adenocarcinoma of the lung.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is known to be a proinflammatory cytokine and glucocorticoid-induced immunomodulator as well as a regulator of tumor growth. Although positive and negative effects of MIF on tumor cell growth have been reported, to the authors' knowledge the precise role of MIF in tumorigenesis remains unclear. In the current study the authors assessed expression of MIF protein and mRNA in lung adenocarcinomas with regard to patient prognosis. METHODS: Immunohistochemical analysis was performed on tissue specimens surgically obtained from 74 patients with primary lung adenocarcinoma (American Joint Committee on Cancer pathologic Stages I, II, and IIIa). In addition, expression of MIF mRNA in the cancerous tissue was investigated using in situ hybridization. Patient prognosis was evaluated with regard to MIF expression levels and its distribution was analyzed with the Kaplan-Meier method. RESULTS: MIF mRNA and MIF protein were observed in the bronchial epithelium, alveolar epithelium, vascular smooth muscle, and alveolar macrophages in the normal lung tissue. In tumor tissue from lung adenocarcinoma specimens, both MIF mRNA and protein were observed at much higher levels than in the normal alveolar epithelium. MIF protein was observed diffusely in the cytoplasm of tumor cells in all tumor specimens examined. MIF protein also was observed in the nuclei of tumor cells from 59 patients (79.7%), whereas it was not observed in the nuclei of tumor cells from 15 patients (20.3%). The patients without nuclear MIF expression had a worse prognosis compared with those patients with MIF expression in the nuclei (P = 0.04). CONCLUSIONS: The results of the current study suggest that intracellular MIF distribution predicts patient prognosis in individuals with adenocarcinoma of the lung.

Adenocarcinoma↗

Selective vulnerability of spinal motor neurons to reactive dicarbonyl compounds, intermediate products of glycation, in vitro: implication of inefficient glutathione system in spinal motor neurons.

We investigated the effects of two reactive dicarbonyl compounds, methylglyoxal (MG) and 3-deoxyglucosone (3-DG), on cultured spinal cord neurons. Incubation of cortical and spinal neurons with MG and 3-DG for 24 h induced neuronal death in a dose-dependent manner. Spinal motor neurons were more vulnerable than spinal non-motor neurons and cortical neurons. Treatments with glutathione (GSH)-augmenting agents showed protective effects against MG and 3-DG neurotoxicity. Motor neurons were better protected than non-motor neurons. Cotreatment, but not pretreatment, of aminoguanidine (AG), a known inhibitor of advanced glycation end-products (AGEs) from crosslinking, showed a protective effect on spinal neurons with no difference in protective rates between motor and non-motor spinal neurons. Treatments with GSH depleting agents enhanced the neurotoxicity of MG and 3-DG on spinal neurons. Motor neurons were more vulnerable than non-motor neurons with GSH-depleting treatments prior to MG and 3-DG exposures. These data demonstrate that spinal motor neurons are more vulnerable to dicarbonyl compounds, and this selectivity might be related to the relatively inefficient GSH system in spinal motor neurons.

Amyotrophic Lateral Sclerosis↗

Detection of an Amadori product, 1-hexitol-lysine, in the anterior horn of the amyotrophic lateral sclerosis and spinobulbar muscular atrophy spinal cord: evidence for early involvement of glycation in motoneuron diseases.

Glycation is a series of non-enzymatic reactions initiated by addition of reducing sugars to epsilon-amino group of lysine residues and alpha-amino group of the N terminus of proteins, leading to the formation of advanced glycation end products (AGE). It is thought to be involved in aging and various neurodegenerative conditions. In the present study using anti-1-hexitol-lysine (1-HL) antibody, Amadori product, an early glycation product, was detected in axonal spheroids in the anterior horn of amyotrophic lateral sclerosis and in atrophic neurons of spinobulbar muscular atrophy (SBMA, Kennedy disease with abnormally expanded triplet repeats in androgen receptor gene) but not in other regions of the central nervous system. Furthermore, Amadori product was undetectable in the tissues from age-matched controls. Thus, 1-HL formation could not reflect physiological aging.

Amyotrophic Lateral Sclerosis↗

Graft-versus-host-disease-associated donor cell engraftment in an F1 hybrid model is dependent upon the Fas pathway.

The graft-versus-host disease (GVHD) generated in BDF1 mice by the injection of spleen cells from the C57BL/6 parental strain induces a direct cell-mediated attack on host lymphohaematopoietic populations, resulting in the reconstitution of the host with donor cells. We examined Fas-Fas ligand (FasL) interactions in donor and host haematopoietic cells over a prolonged period of parental-induced GVHD. Fas expression on bone marrow cells of both donor and host origin increased at 2 weeks. Host cell incubation with anti-Fas antibody induced apoptosis, and the number of haematopoietic progenitor cells decreased. Fas-induced apoptosis by the repopulating donor cells, however, did not increase until 12 weeks, when more than 90% of the cells were donor cells. The expression of various cytokines, such as interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), and FasL gene expression in the bone marrow increased concomitantly. To examine directly whether FasL has a major role in the development of donor cell engraftment, FasL-deficient (gld) mice were used as donors. Injection of B6/gld spleen cells induced significantly less host lymphohaematopoietic depletion, resulting in a failure of donor cell engraftment. Furthermore, injection of IFN-gamma gene knockout (gko) B6 spleen cells failed to augment Fas and FasL expression in recipient mice, resulting in a failure of donor cell engraftment. This suggests that the induction of apoptosis by Fas-FasL interactions in host cells may contribute to a reconstitution of the host with donor cells and that donor-derived IFN-gamma plays a significant role for Fas-FasL interactions in host cells during parental-induced GVHD.

Animals↗

Characteristics of epilepsy in severely mentally retarded individuals.

In order to clarify the characteristics of epilepsy in patients with severe mentally retarded (SMR) subjects, we analyzed 52 SMR subjects with epilepsy from the institute for SMR subjects at Kikuchi National Hospital, Kumamoto, Japan. A total of 61.5% patients had uncontrolled seizures which were resistant to treatment. The most common combinations of seizure types in those not responding to conventional anticonvulsants were generalized tonic-clonic seizures (GTCS) with tonic seizure and GTCS with atypical absence. Their clinical features were characterized by spastic paralysis associated with a slower background electroencephalogram and abnormal computed tomography scans of the head, suggesting the involvement of cortical damage. These findings suggest that a large proportion of epilepsy in SMR subjects does not respond to treatment and that the severity of organic brain damage may therefore affect the natural course of epilepsy in such patients.

Adolescent↗

A psychosocial approach to epileptic patients.

A psychoeducational approach was taken with 174 epileptic patients. Using this approach, no family problems were recognized among patients with idiopathic generalized epilepsy (IGE) or among those with symptomatic generalized epilepsy (SGE). However, 11 patients with temporal lobe epilepsy (TLE) and I patient with non-temporal lobe epilepsy (non-TLE) did exhibit family problems indicating that such problems involving IGE or SGE cases can be prevented through educational programs using a psychoeducational approach. This fails, however, to prevent such problems for TLE or non-TLE cases. Furthermore, small group psychotherapy was given to 10 patients with intractable TLE. They were directed to make self-evaluations regarding therapeutic factors originally introduced by Yalom but specially modified for these particular patients. Relatively high evaluations were given on every factor when compared with the results of individual psychotherapy. These results point out the importance of providing such psychotherapeutic approaches as group psychotherapy and self-help groups in addition to educational programs in order to enhance the quality of life (QOL) of epileptic patients and their families.

Epilepsy↗