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Biomedical subjects

H Yamauchi

Publications and source records attributed to H Yamauchi.

At least 163 records · Page 9Linked to original sources

Characterization of anti-human interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) monoclonal antibodies and their application in the measurement of human IL-18 by ELISA.

Interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) is a novel cytokine, which is a potent inducer of IFN-gamma production and plays an important role in Th1 responses. In order to develop a specific ELISA for the measurement of human IL-18, we established 13 anti-human IL-18 monoclonal antibodies and characterized them. 7 murine anti-human IL-18 mAbs and 6 rat anti-human IL-18 mAbs were obtained by fusion of splenocytes from mice or rats immunized with human IL-18, with SP2/0 myeloma cells. These antibodies were classified into 4 groups according to competitive binding ELISAs to the human IL-18 molecule. 1 murine mAb and all 6 rat mAbs neutralized IFN-gamma production induced by IL-18. A specific human IL-18 ELISA was developed using two neutralizing mAbs (#125-2H and #159-12B). This ELISA detects human IL-18 with a minimum detection limit of 10 pg/ml, but does not react with heat-denatured human IL-18. The ELISA does not show any cross-reactivity with other cytokines. Using this assay, human IL-18 was measurable in the plasma of leukemia patients. This ELISA would become a powerful tool for investigating the relationship between IL-18 and various diseases or analyzing the control mechanisms of IL-18 production from IL-18 producing cells.

Adult↗

Production of IL-18 (IFN-gamma-inducing factor) messenger RNA and functional protein by murine keratinocytes.

Recently, the novel cytokine IL-18 (IFN-gamma-inducing factor) has been described as a growth and differentiation factor for Th1 cells. Epidermal keratinocytes (KC) are known to direct T cell education by production of cytokines. Therefore, expression of IL-18 was sought in KC. Epidermal RNA was analyzed following stimulation with contact sensitizers or controls for IL-18 mRNA expression by semiquantitative reverse transcription-PCR. Constitutive expression of IL-18 mRNA was low in untreated epidermal cells (EC), but early up-regulation of IL-18 mRNA signals was detected following application of a contact allergen in vivo. The peak strength of IL-18 signals was observed within 4 to 6 h following stimulation with an allergen. Application of an irritant (benzalconiumchloride) or solvents did not result in increased signal strength. To determine the cellular origin of IL-18 mRNA in EC, depletion experiments were performed. IL-18 signals were not affected by depletion with anti-CD3 (T cells) or anti-MHC class II mAb-coupled beads identifying KC as a major source of IL-18. These results were confirmed by analysis of mRNA derived from the KC cell line PAM 212. Strong IL-18 signals could be detected by reverse transcription-PCR. To delineate whether IL-18 protein was produced by EC/KC, a sandwich ELISA was used to assay for IL-18 production. Supernatants from allergen-stimulated EC and KC showed production of IL-18 protein. To confirm that IL-18 protein was functional, EC or KC supernatants were tested for their ability to induce IFN-gamma production. Significant amounts of IFN-gamma were detected in supernatants of allergen-treated cells. In aggregate, our data indicate that murine KC are a source of both IL-18 mRNA and functional protein.

Animals↗

Brain functional activity during gait in normal subjects: a SPECT study.

The purpose of this study was to evaluate changes in brain activity during voluntary walking in normal subjects using technetium-99m-hexamethyl-propyleneamine oxime single photon emission computed tomography. This study included 14 normal subjects. Statistical parametric mapping analysis revealed that the supplementary motor area, medial primary sensorimotor area, the striatum, the cerebellar vermis and the visual cortex were activated. These results suggested that the cerebral cortices controlling motor functions, visual cortex, basal ganglia and the cerebellum might be involved in the bipedal locomotor activities in humans.

Adult↗

Interleukin-6 and a delay of neutrophil apoptosis after major surgery.

Surgical treatments affect host immune systems. Apoptosis of the circulatory lymphocytes and an elevation of the number of neutrophils are induced by surgery. These alterations are not dependent only on the stress hormone. The course of neutrophilia and the serum concentration of interleukin-6 are given after various surgical treatments. Neutrophil-mediated lung injury is discussed.

Apoptosis↗

Atrophy of the corpus callosum, cognitive impairment, and cortical hypometabolism in progressive supranuclear palsy.

Recent studies disclosed neurofibrillary degeneration in layer 3 of the association cortex in patients with progressive supranuclear palsy. This lesion may be associated with corpus callosum atrophy and may impair the function of cortical regions indispensable for complex cognitive activity. To investigate whether corpus callosum atrophy is associated with cognitive impairment and cerebral cortical hypometabolism, we studied 10 patients with progressive supranuclear palsy using magnetic resonance imaging and positron emission tomography with fluorodeoxyglucose as a tracer. Compared with 23 age-matched control subjects, the patients had significantly decreased callosal area-skull area ratios, with anterior predominance of the degree of atrophy. The corpus callosum atrophy was accompanied by a decreased mean cortical glucose metabolic rate, predominantly in the frontal region of the cortex, and poor performance on the picture arrangement subtest of the Wechsler Adult Intelligence Scale and the verbal fluency task. We conclude that corpus callosum atrophy with anterior predominance is present in progressive supranuclear palsy, and that this atrophy is associated with cognitive impairment and cerebral cortical hypometabolism, especially in the frontal cortical region. Corpus callosum atrophy may reflect the pathological changes in the cerebral cortex, accentuated in the frontal region, that contribute to the development of frontal lobe dysfunction in this disease.

Aged↗

Cerebral glucose metabolism in corticobasal degeneration: comparison with progressive supranuclear palsy and normal controls.

The regional metabolic rate of glucose was estimated using 18F-labeled 2-deoxyglucose and positron-emission tomography (PET) in eight patients with corticobasal degeneration (CBD). Measures of cerebral glucose metabolism in these patients were compared with those for nine age-matched normal controls and eight patients with progressive supranuclear palsy (PSP). Compared with that in the normal controls, the CBD patients showed significantly reduced cerebral glucose metabolism in the contralateral hemisphere to the clinically most affected side in the dorsolateral frontal, medial frontal, inferior parietal, sensorimotor, and lateral temporal cortex, as well as in the corpus striatum and the thalamus. In comparison with that in PSP, in CBD the glucose metabolism in the contralateral hemisphere was significantly decreased in the inferior parietal, sensorimotor, lateral temporal cortex, and the corpus striatum. These results confirm the marked asymmetric cerebral involvement in CBD and suggest that there are significant differences between CBD and PSP in the cerebral metabolism in some cerebral regions such as the inferior parietal cortex and sensorimotor cortex, which might reflect the differences in their clinical characteristics.

Aged↗

Age-related changes in cerebral blood flow activation during a Card Sorting Test.

To determine the age-related changes in the neural processing involved in the Modified Card Sorting Test (MCST), we measured cerebral blood flow (CBF) during performance of the MCST and of the number-matching task in young and elderly subjects using positron emission tomography. Compared with that during the number-matching task, CBF during the MCST was increased in the left dorsolateral prefrontal cortex (DLPFC), left inferior parietal lobule, and left striate and prestriate cortices in both age groups. However, CBF activation in these areas was significantly lower in the elderly subjects than the young subjects. Furthermore, CBF activation was reduced in the left DLPFC, right parahippocampal gyrus, and prestriate cortex in proportion to the increase in the number of perseverative errors with aging. These results suggest that the impaired MCST performance in elderly subjects may be due, in part, to dysfunction of the network involving certain cortical areas such as the prefrontal and parahippocampal cortices, although the essential neural circuits for MCST performance were still preserved even in the elderly subjects.

Adult↗

Hormone-cytokine response. Pneumoperitoneum vs abdominal wall-lifting in laparoscopic cholecystectomy.

BACKGROUND: Changes in blood hormone and cytokine were investigated in patients who underwent laparoscopic cholecystectomy via insufflation (CO2 group) vs those who had abdominal wall-lifting (Air group). METHODS: Seventeen female patients with cholecystolithiasis were randomly divided into two groups. Peripheral blood samples were obtained during perioperative period, and plasma hormone levels (ACTH, cortisol) and serum cytokine levels (TNFalpha, IL-1beta, IL-6, IL-10) were measured. RESULTS: The number of circulating lymphocytes significantly decreased at 1 h after surgery in both groups, but the decrease in the CO2 group was significantly smaller than that in the Air group. There was no significant difference in hormone elevation between groups. Serum concentrations of IL-6 and IL-10 in the Air group were significantly higher than in the CO2 group. CONCLUSIONS: CO2 insufflation may reduce cytokine production in laparoscopic cholecystectomy.

Abdominal Muscles↗

Subcutaneous transposition of the ovary following hysterectomy.

OBJECTIVES: Preservation of ovarian function at hysterectomy in pre-menopausal women is desirable. A possibly malignant tumor from retained ovary is a concern. We demonstrate a new technique for exteriorization of the ovaries. METHOD: In 27 patients, the infundibulopelvic ligament was mobilized. The retroperitoneal space was then widely opened. The ovary was gently pulled through a fascial incision and fixed on the fascia followed by skin closure. RESULTS: Cystic formation was common (66.7%). Four patients had extreme enlargement of the transposed ovary. A needle puncture revealed intra-ovarian hematomas or fluid retention. One had puncture of the translocated ovary for in vitro fertilization more than two years following transposition. CONCLUSIONS: Possible advantages are (1) early detection and diagnosis of ovarian cysts, (2) easy surgical access to remove ovarian cysts, (3) transposition of ovaries outside the radiation field and (4) in vitro fertilization is facilitated. Comparative study for ovarian function is ongoing.

Abdomen↗

Treatment of acute myeloid leukemia and myelodysplastic syndrome with orally administered cytarabine ocfosfate and granulocyte colony-stimulating factor.

Cytarabine ocfosfate (SPAC) was administered orally to 19 patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). SPAC was administered at doses of 200-300 mg/day for more than 14 days with granulocyte colony-stimulating factor (G-CSF). Four of the 12 patients with AML and 1 of the 7 patients with MDS achieved complete remission (CR) after one cycle of SPAC treatment. Especially, 3 of the 6 patients with newly diagnosed AML achieved CR. Major side effects of SPAC were myelosuppression and tolerable gastrointestinal disorders. The treatment with SPAC is a therapeutic option in elderly patients or patients with organ failure.

Administration, Oral↗

Continuous transoesophageal echocardiography monitoring during weaning from cardiopulmonary bypass in children.

The purpose of this study was to evaluate the effectiveness of transoesophageal echocardiography monitoring during weaning from cardiopulmonary bypass after intracardiac repair in children. The left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricle wall motion were monitored continuously by transoesophageal echocardiography in controls weaned easily from cardiopulmonary bypass (group A, n = 25), and those weaned with difficulty from cardiopulmonary bypass after mechanically assisted circulation (group B, n = 16). In group A, left ventricular ejection fraction and left ventricle wall motion were within normal range, and did not change significantly during weaning after cardiopulmonary bypass when compared with pre-bypass data. In contrast, left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricle wall motion in group B during the first trial of weaning from bypass were significantly worsened. Hence, assisted circulation was performed until the data obtained via transoesophageal echocardiography improved with regard to maintenance of fluid balance, catecholamine dosage and assisted pump flow. All cases in group B were weaned safely from cardiopulmonary bypass despite their critical condition. In conclusion, continuous transoesophageal echocardiography monitoring may be a useful tool in children with severe heart failure for safe weaning from cardiopulmonary bypass after intracardiac repair.

Adolescent↗

Effects of stimulated free latissimus dorsi muscle graft on LVEDV and LVSW: a new dynamic cardiomyoplasty technique.

The effectiveness of dynamic cardiomyoplasty (DCMP) remains controversial. We hypothesized that effectiveness of DCMP using the latissimus dorsi muscle graft (LDMG) depends on the wrapping method. We analyzed pressure-volume relations (PVR), the left ventricular stroke work (LVSW), and the left ventricular end diastolic volume (LVEDV) changes during nonstimulation and stimulation of the LDMG to evaluate the effect of a new wrapping method of DCMP on the LVSW and the LVEDV changes. The new wrapping technique was evaluated in an acute animal experimental model. In 12 mongrel dogs, we performed continuous measurement of the dimensional and pressure dates of the left ventricle (LV) after the DCMP. The measurement was performed 15 min after wrapping during 5 periods. The duration of one measurement period was 15 s. The animals were divided into 2 groups according to the wrapping method. The heart was wrapped with the LDMG using 2 different methods. For Method 1, Carpentier's method, the heart was wrapped primarily with the distal part of the LDMG, the lateral segment. The vasculoneural pedicle of the latissimus dorsi muscle (LDM) was preserved. For Method 2, the LDM was separated, and the vasculoneural pedicle was cut. The medical sternotomy was performed. The thoracodorsal artery of LDMG was anastomosed to the right internal mammary artery, and the thoracodorsal vein was anastomosed to the right atrial appendage. The heart was wrapped primarily with the proximal part of the "free LDMG," the transverse segment. Based on the PVR loops, the changes of the LVSW and the LVEDV in both experimental groups were analyzed. The paired t-test was used for statistical analysis. Using Method 1, the LVSW and the LVEDV showed no significant changes during stimulation (stim) of the LDMG, compared with nonstimulation (nonstim) (LVSW: nonstim, 970 +/- 168 erg x 10(3); stim, 1,181 +/- 203 erg x 10(3); p = 0.126 and LVEDV: nonstim, 36.6 +/- 6.7 ml; stim, 37.2 +/- 6.8 ml; p = 0.36). Using Method 2, the LVSW was increased, and the LVEDV was decreased during stimulation of the free LDMG, compared with nonstimulation (LVSW: nonstim, 694 +/- 117 erg x 10(3); stim, 846 +/- 104 erg x 10(3); p < 0.001 and LVEDV: nonstim, 47.7 +/- 2.8 ml; stim, 46.8 +/- 2.7 ml; p < 0.001). The stimulated free LDMG wrapping of the heart seems to be a more effective wrapping method for DCMP, and it results in an increase of the LVSW and a decrease of the LVEDV, compared with the original Carpentier's method.

Animals↗

Assessment of benzodiazepine receptors using iodine-123-labeled iomazenil single-photon emission computed tomography in patients with ischemic cerebrovascular disease. A comparison with PET study.

BACKGROUND AND PURPOSE: [123I]Iomazenil (IMZ) is a tracer used for single-photon emission computed tomography (SPECT) that has the characteristics of selectively binding to central benzodiazepine receptors (BZR) in the neuron membrane. To determine whether IMZ SPECT provides new information on assessing neuronal damage after ischemic insult to the brain, we compared IMZ SPECT images with the cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and cerebral metabolic rate of glucose (CMRGlc) studied by position emission tomography in the chronic stage of ischemic stroke. METHODS: Five patients (male; mean age, 63.2 +/- 6.0 years) with ischemic cerebrovascular disease and 6 age- and sex-matched normal control subjects were studied. IMZ images obtained 180 minutes after injection were analyzed for BZR binding, and these images were compared with the CBF, CMRO2, and CMRGlc obtained by position emission tomography in the same perfusion areas both visually and quantitatively. RESULTS: In the visual analysis of data obtained from 4 patients with subcortical infarction, decreased IMZ accumulation was observed locally in the overlying normal-appearing cortices of the affected hemisphere, where extensive hypoperfusion and hypometabolism were seen on the images of CBF, CMRO2, and CMRGlc. The regional relative IMZ uptake (regional to cerebellar ratio) for all 5 patients was significantly correlated with the corresponding regional CMRO2 values (r = .45, P < .05). However, no significant correlation was found of the IMZ uptake with either the regional CBF or the regional CMRGlc. CONCLUSIONS: The use of IMZ SPECT provides new information on the neuronal alteration induced by chronic ischemic cerebrovascular disease.

Aged↗

Impairment of neural nitric oxide-mediated relaxation after antigen exposure in guinea pig airways in vitro.

Nitric oxide (NO), a neurotransmitter of inhibitory nonadrenergic noncholinergic (iNANC) nerves in airways, is a radical with a short half-life, and its function may be modified by airway inflammation. To test this hypothesis, we examined whether airway allergic inflammation affects iNANC responses mediated by NO in guinea pigs in vitro. Animals sensitized with ovalbumin (OA) were challenged with 0.03% OA (OA group) or saline (saline group) by inhalation on 3 consecutive days. On the day after the final challenge, iNANC responses elicited by electrical field stimulation (2 to 16 Hz) or relaxation responses to 3-morpholinosydnonimine (SIN-1), 10(-8) to 10(-4) M, were obtained in the tracheal strips precontracted by histamine (3 x 10(-6) M) in the presence of atropine and propranolol (both 10(-6) M). The INANC responses of the OA group were significantly attenuated compared with those of the saline group (p < 0.05), and the inhibitory effect of a NO synthase (NOS) inhibitor, Nm-nitro-L-arginine methyl ester, on the INANC responses was abolished in the OA group. SIN-1-induced tracheal smooth muscle relaxation was also significantly affected by antigen exposure (p < 0.05), the effect of which disappeared in the presence of a NO scavenger, carboxy PTIO (3 x 10(-6) M). The impairment of the INANC responses after antigen exposure was significantly restored by superoxide dismutase (1,000 U/ml), especially at lower frequencies. Histochemical demonstration of NADPH-diaphorase-positive nerves representing neural NOS density was not different between the two groups. These results suggest that allergic airway inflammation impairs neural NO-induced relaxation, presumably by inhibiting the access of neural NO to the airway smooth muscle.

Animals↗

Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels of extracellular domain of the HER-2/c-neu protein.

PURPOSE: Overexpression of the HER-2/c-neu/c-erbB2 proto-oncogene is associated with a worse prognosis in patients with breast cancer, perhaps due to an association of the HER-2 proto-oncogene protein with resistance to hormone and/or chemotherapy. Circulating levels of the extracellular domain (ECD) of the HER-2/c-neu-related protein (NRP) are elevated in 20% to 40% of patients with metastatic breast cancer. We investigated whether pretreatment levels of NRP predict response to hormone therapy (HT). MATERIALS AND METHODS: Circulating NRP levels were determined in 94 patients who participated in a randomized trial of three different doses of the antiestrogen, droloxifene (DRO), as first-line HT for metastatic breast cancer. RESULTS: NRP levels were elevated (> or = 5,000 U/mL) in 32 of 94 patients (34%). Only three of 32 patients (9%) with elevated NRP levels responded to DRO, compared with 35 of 62 (56%) with nonelevated NRP levels (P = .00001). Low pretreatment NRP level was the most powerful predictor of response to DRO (odds ratio of response, 22.4; P = .0001). Elevated pretreatment NRP levels were also associated with a shorter time to progression (TTP) and survival duration. CONCLUSION: Pretreatment circulating NRP levels predict a low likelihood of benefit from HT, specifically DRO, in patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive or receptor-unknown metastatic breast cancer, even when adjusted for other known predictive factors, such as ER and/or PgR levels, site of disease, disease-free interval from primary treatment to recurrence, and prior adjuvant chemotherapy. These data suggest that pretreatment NRP levels may be useful in deciding whether to treat a patient who otherwise appears to be likely to respond to HT.

Aged↗

Inflammatory abdominal aortic aneurysms and atherosclerotic abdominal aortic aneurysms--comparisons of clinical features and long-term results.

A total of 274 patients with abdominal aortic aneurysms due to atherosclerosis (AAA) and 16 patients with inflammatory abdominal aortic aneurysms (IAAA) were reviewed to compare and contrast the clinical characteristics of the 2 groups. The AAA group comprised 243 men and 31 women with a mean age of 69.2 +/- 0.4 (range 51-86) years. The IAAA group comprised 15 men and 1 woman with a mean age of 67.4 +/- 2.0 (range 53-81) years. Most patients with IAAA (12/16; 75.0%) had pain at presentation, whereas only 37 out of 274 patients (13.5%) with AAA had pain (p < 0.001). Fifty out of 274 patients (18.2%) with AAA were asymptomatic, the most common principal complaint being a pulsatile tumor, which was found in 150 out of 274 patients (54.7%; p < 0.005 vs IAAA). Regarding laboratory findings of inflammation, preoperative erythrocyte sedimentation rate values were elevated in 15 out of 16 (93.8%) patients, and C-reactive protein values were elevated in 13 out of 16 (81.3%) patients with IAAA. The incidence of perioperative complications was similar in the 2 groups. The 30-day postoperative mortality among AAA patients was 6.2% (17/274 cases), including 12 cases of non-ruptured and 5 cases of ruptured AAA; in contrast, no early deaths occurred among patients with IAAA. The cumulative 5-year survival rate was 80.2% for IAAA patients and 74.6% for AAA patients (NS). The results of our review suggest that careful diagnosis and intra- and postoperative management could lead to patients with IAAA having a similar survival rate to those with AAA.

Aged↗