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Biomedical subjects

H Okada

Publications and source records attributed to H Okada.

At least 199 records · Page 11Linked to original sources

Vitamin B6 deficiency in elderly patients on chronic peritoneal dialysis.

Polyneuropathy is one of the most frequent manifestations in chronic uremia. Among the factors related to polyneuropathy, vitamin B6 deficiency is well known. The exact prevalence of vitamin B6 deficiency related to neurological manifestations has not been previously reported. We studied vitamin B6 status, collected self-reported symptoms, and carried out full neurological examinations in 66 patients on chronic peritoneal dialysis. Vitamin B6 status was estimated by direct measurement of pyridoxal phosphate. In general, symptoms related to vitamin B6 deficiency are peripheral neuropathies, such as paresthesia, burning and painful dysesthesias, and thermal sensations. These symptoms were reported and assigned one of five grade scores. Of our 66 patients, 12 patients complained at least one sensory abnormality. The levels of vitamin B6 in the patients varied between 1.0 ng/mL and 30 ng/mL. Patients who complained of neurological symptoms owing to vitamin B6 deficiency were significantly older than the other patients. In analyzing the symptomatic cases before and after vitamin B6 supplementation, a significant correlation was seen between the level of vitamin B6 and symptoms. Within one month after initiation of oral vitamin B6 supplementations (30 mg daily), levels of pyridoxal phosphate rose, and sensory abnormalities improved in 8 of 12 patients. When peripheral neuropathy is suspected in elderly patients on chronic peritoneal dialysis, vitamin B6 deficiency should be taken into consideration as the cause. If vitamin B6 deficiency is appropriately treated by oral supplementation, sensory abnormalities can be eliminated.

Adolescent↗

[J-sternotomy approach for aortic valve reoperation].

Recent progress in cardiovascular surgery has promoted less non-invasive surgery. We reoperated in a forty-two year old female for aortic valve regurgitation using the J-sternotomy approach and experienced good results. The patient was operated on with AVR 12 years after her first cardiac operation. Chest computed tomography revealed an adhesion between the anterior chest wall and the right ventricle. We made a sternal incision from the sternal notch down to the fourth right intercostal space (J-sternotomy). Ascending aorta was cannulated in the conventional manner. A conventional Two-stage cannula was placed in the auricle of the right atrium. A venting tube was also cannulated through the right upper pulmonary vein. J-sternotomy and minimal adhesionectomy made for a good operative field to establish cardiopulmonary bypass and to perform aortic valve re-operation.

Adult↗

Blood pressure reduction associated with preservation of renal function in hypertensive patients with IgA nephropathy: a 3-year follow-up.

BACKGROUND: The relative importance of hypertension in the progression of renal failure is well understood. Recently, several studies have provided evidence that antihypertensive therapy enhances renal survival. However, the specific antihypertensive drug regimens that are most effective in generating such long-term effects remain controversial. PATIENTS AND METHODS: Forty-nine hypertensive IgA nephropathy (IgAN) patients (39 +/- 7 years old, serum creatinine 1.1 +/- 0.2 mg/dl) with proteinuria received antihypertensive therapy with angiotensin-converting enzyme inhibitors (ACEi: 2.5-10 mg of benazapril daily) and calcium channel blockers (CCBs: 2.5-10 mg amlodipine daily) for 3 years. The patients' blood pressures in group one were controlled below 140/85 mmHg by increases in their first drug dose or by addition of the second drug in group 1. Blood pressures for patients in group 2 were controlled using the same two options, except to levels below 130/70 mmHg. Patients within the two groups were selected and controlled with regard to sex, age, and serum creatinine. The renal protective effects of each protocol were evaluated in terms of reductions in creatinine clearance. After 3 years of the above outlined blood pressure control regimens, the reductions in creatinine clearance were compared. RESULTS: Creatinine clearances decreased in group 1 patients (from 85.7 +/- 2.4 ml/min to 72.9 +/- 2.4 ml/min, p < 0.05). On the other hand, creatinine clearance remained essentially unchanged for patients in group 2 (from 87.2 +/-4.7 ml/min to 85.9 +/- 5.9 ml/min). Although creatinine clearance in both groups was almost the same at the start of study, there was a significant difference between them by the conclusion of the study (p < 0.05). Proteinuria and hematuria did not change significantly throughout the study and there were no significant differences in these respects between these two corresponding groups. There were no significant differences between the groups with reference to side-effects or complications. CONCLUSION: These data provide evidence that reducing blood pressure has protective renal effects in cases of mild renal insufficiency with hypertension in IgA nephropathy.

Adult↗

[Outcomes of home anti-cancer chemotherapy--estimation of hepatic arterial infusion chemotherapy for patients with multiple liver metastases].

A total of 18 patients (13: colon cancer, 5: gastric cancer) with multiple liver metastases (H3) underwent hepatic arterial infusion chemotherapy (HAI) using an implanted arterial port with portable syringe pumps in our outpatient clinic. Clinical perspective: overall response rate was 22.2% (CR: 1 case, PR: 3 cases (1 case: hepatectomy after HAI), NC: 12 cases, PD: 2 cases), however, 7 of 12 cases of NC were long NC (more than 6 months). No major complications with HAI were experienced. Patient Perspective: After HAI in our outpatient clinic, the 50% survival was 341 days, 50% hospital free days were 319 days and home stay rate was 92.9%. Societal Perspective: cost and hospital stay days were significantly reduced. Home anti-cancer chemotherapy using HAI for gastrointestinal cancer patients with multiple liver metastases was safe and efficient from the viewpoint of medical outcomes.

Aged↗

Diagnostic value of MRI for the female urethral diverticulum.

A woman, who discharged pus at the time of intercourse, was diagnosed to have a urethral diverticulum by combination of urethroscope and MRI. MRI provided clear view of the diverticulum in terms of the relationship with the surrounding organs.

Adult↗

Successful treatment of disseminated Fusarium infection in an infant with leukemia.

Disseminated Fusarium infection in an immunocompromised host is intractable and results in high mortality. We provide the first full case report on successful treatment of a disseminated Fusarium infection in an infant. The 6-month-old infant, whose family raised livestock, had infantile leukemia. During the neutropenic period after intensive chemotherapy, vomiting, diarrhea, fever, subcutaneous nodes, and coughing appeared. Pneumonia was diagnosed, and Fusarium moniliforme was isolated from blood culture. A central venous catheter was removed. Granulocyte colony-stimulating factor (G-CSF) and amphotericin B (AMPH-B) (total dose, 65 mg/kg) were administered continuously for 8 weeks. The infection was resolved according to improvement of clinical and laboratory findings, and intensive chemotherapy was restarted for the leukemia. Cord blood stem cell transplantation from an unrelated donor was performed. The Fusarium infection did not recur, but after transplantation, leukemia relapsed. Treatment of neutrophils using G-CSF, AMPH-B, and local treatment induced resolution of the disseminated Fusarium infection in this immunocompromised host with malignancy. We suggest caution for patients living in an environment conducive to the development of Fusarium infection because of the particular risk of infection.

Amphotericin B↗

Tyrosine phosphorylation of shc in response to B cell antigen receptor engagement depends on the SHIP inositol phosphatase.

Tyrosine phosphorylation of Shc in response to B cell Ag receptor (BCR) engagement creates binding sites for the Src homology 2 (SH2) domain of Grb2. This facilitates the recruitment of both Grb2. Sos complexes and Grb2. SHIP complexes to the plasma membrane where Sos can activate Ras and SH2 domain-containing inositol phosphatase (SHIP) can dephosphorylate phosphatidylinositol 3,4,5-trisphosphate. Given the importance of Shc phosphorylation, we investigated the mechanism by which the BCR stimulates this response. We found that both the SH2 domain and phosphotyrosine-binding (PTB) domain of Shc are important for BCR-induced tyrosine phosphorylation of Shc and the subsequent binding of Grb2 to Shc. The unexpected finding that the PTB domain of Shc is required for Shc phosphorylation was investigated further. Because the major ligand for the Shc PTB domain is SHIP, we asked whether the interaction of Shc with SHIP was required for BCR-induced tyrosine phosphorylation of Shc. Using SHIP-deficient DT40 cells, we show that SHIP is necessary for the BCR to induce significant levels of Shc tyrosine phosphorylation. BCR-induced tyrosine phosphorylation of Shc could be restored in the these cells by expressing wild-type SHIP but not by expressing a mutant form of SHIP that cannot bind to Shc. This suggests that BCR-induced tyrosine phosphorylation of Shc may depend on the binding of SHIP to the Shc PTB domain. Thus, we have described a novel role for SHIP in BCR signaling, promoting the tyrosine phosphorylation of Shc.

Adaptor Proteins, Signal Transducing↗

C5a receptor expression by TGW neuroblastoma cells.

We recently reported that not only lymphoid cells, but cells of neuronal origin may harbor C5a receptors (C5aR) as suggested by results of RT-PCR testing and that an apoptotic pathway is associated with the C5aR. To determine whether C5aR is expressed as an integral membrane protein, we generated mono- and polyclonal anti-C5aR antibodies. Flow cytometry showed a low-level expression of C5aR in TGW neuroblastoma cells. Epitope mapping suggested that a conformation change in C5aR occurs when exposed to C5a. Although an aphysiologically high concentration of C5a is necessary for inducing a transient increase in the intracellular Ca2+ level, TGW cells do employ the signal transduction pathway associated with C5aR, suggesting that these cells may serve as putative model for C5aR-expressing neurons.

Antigens, CD↗

Thiazolidinedione inhibits production of RANTES in a cytokine-treated human lung epithelial cell line.

The chemokine RANTES is a potent chemoattractant for eosinophils. RANTES is produced by lung epithelial cells during eosinophil-rich inflammatory diseases such as asthma. In this study, we examined the effects of thiazolidinediones (TZD) on RANTES expression in a human lung epithelial cell line, A549. In A549 cells, interleukin-1beta and tumor necrosis factor-alpha induced endogenous RANTES protein secretion, mRNA expression, and promoter activity. The TZD inhibited these effects. Our data indicate that the suppression of the expression of RANTES can be accomplished by TZD treatment, raising the possibility that TZD might be of therapeutic value in diseases such as asthma.

Cell Line↗

Inhibition of a membrane complement regulatory protein by a monoclonal antibody induces acute lethal shock in rats primed with lipopolysaccharide.

Rats pretreated with traces of LPS developed acute fatal shock syndrome after i.v. administration of a mAb that inhibits the function of a membrane complement regulatory molecule. Such a shock was not observed after the administration of large amounts of LPS instead of the mAb following LPS pretreatment. The lethal response did not occur in rats depleted of either leukocytes or complement, and a C5a receptor antagonist was found to inhibit the reaction. Furthermore, LPS-treated rats did not suffer fatal shock following the injection of cobra venom factor, which activates complement in the fluid phase so extensively as to exhaust complement capacity. Therefore, complement activation on cell membranes is a requirement for this type of acute reaction.

Acute Disease↗

Inhibitory modulation of B cell receptor-mediated Ca2+ mobilization by Src homology 2 domain-containing inositol 5'-phosphatase (SHIP).

Src homology 2 domain-containing inositol 5'-phosphatase (SHIP) mediates inhibitory signals that attenuate intracellular Ca2+ mobilization in B cells upon B cell receptor (BCR) stimulation. To clarify the mechanisms affected by SHIP, we analyzed Ca2+ mobilization in the DT40 B cell line in which the SHIP gene was disrupted. In SHIP-deficient cells, Ca2+ transient elicited by BCR stimulation was more prolonged than that in control cells both in the presence and absence of extracellular Ca2+. Inositol 1,4, 5-trisphosphate production following BCR stimulation was enhanced in SHIP-deficient cells. In SHIP-deficient cells in comparison with the control cells, BCR stimulation in the absence of extracellular Ca2+ induced a greater degree of Ca2+ store depletion and the Ca2+ influx upon re-addition of extracellular Ca2+ was also greater. However, store-operated Ca2+ influx (SOC) elicited by thapsigargin-induced store depletion was not affected by SHIP. These results indicate that the primary target pathway of SHIP is the Ca2+ release from the stores, and that Ca2+ influx by the SOC mechanism is secondarily controlled by the level of Ca2+ in the stores without direct inhibition of SOC. In this way, SHIP may play an important role in ensuring the robust tuning of Ca2+ signaling in B cells.

Animals↗

The effect of aniracetam on cerebral glucose metabolism in rats after lesioning of the basal forebrain measured by PET.

To evaluate the effect of aniracetam, a potent modulator of the glutamatergic and cholinergic systems, on the altered cerebral glucose metabolism after lesioning of the basal forebrain, we measured the cerebral metabolic rate of glucose (CMRGlc) with positron emission tomography and the choline acetyltransferase (ChAT) activity in the frontal cortex of the lesioned rats after treating them with aniracetam. Continuous administration of aniracetam for 7 days after the surgery prevented CMRGlc reduction in the frontal cortex ipsilateral to the lesion while the lesioned rats without aniracetam showed significant CMRGlc reduction in the frontal cortex. The level of CMRGlc in the lesion-side basal forebrain was lower in all rats regardless of the aniracetam treatment. Biochemical studies showed that aniracetam did not alter the reduction in the frontal ChAT activity. These results showed that aniracetam prevents glucose metabolic reduction in the cholinergically denervated frontal cortex with little effect on the cortical cholinergic system. The present study suggested that a neurotransmitter system other than the cholinergic system, e.g. the glutamatergic system, plays a central role in the cortical metabolic recovery after lesioning of the basal forebrain.

Animals↗

Nasopharyngeal-associated lymphoreticular tissue (NALT) immunity: fimbriae-specific Th1 and Th2 cell-regulated IgA responses for the inhibition of bacterial attachment to epithelial cells and subsequent inflammatory cytokine production.

To investigate the antibacterial activity of mucosal Th1 and Th2 immune responses induced nasally and orally, mice were immunized with mucosal vaccine containing fimbrial protein of Porphyromonas gingivalis, a causative agent for a destructive chronic inflammation in the periodontium, and cholera toxin (CT) as mucosal adjuvant. Nasal vaccine containing low doses of fimbriae (10 micrograms) and CT (1 microgram) induced Ag-specific Th1/Th2-type response in CD4+ T cells in mucosal effector tissues, including nasal passage and submandibular glands, which accounted for the generation of Ag-specific IgA-producing cells. In contrast, oral immunization required higher amounts of fimbriae and CT for the induction of Ag-specific IgA responses. Fimbriae-specific IgA mAbs generated from submandibular glands of nasally immunized mice inhibited P. gingivalis attachment to and reduced subsequent inflammatory cytokine production from epithelial cells. These findings suggest that nasal vaccination is an effective immunization regimen for the induction of Ag-specific Th1 and Th2 cell-driven IgA immune responses that possess the ability to inhibit bacterial attachment to epithelial cells and subsequent inflammatory cytokine production.

Animals↗

Complement-mediated anti-HIV-1 effect induced by human IgM monoclonal antibody against ganglioside GM2.

HIV-infected cells aberrantly express a high level of antigenic glycosidic structures such as GM2 and Gg4. Some normal sera containing natural IgM Abs to GM2 and/or Gg4 cause C-mediated cytolysis of HIV-infected cells. In the present study we demonstrated that a human IgM anti-GM2 mAb (L55 Ab) can induce cytolysis of HIV-infected cells. Increased GM2 expression by HIV-1 infection of a human T cell line (MOLT4), a human monocyte cell line (U937), and human lymphoblastoid cells was confirmed by immunofluorescence staining with L55 Ab. These infected cells were readily lysed by L55 Ab in the presence of fresh human serum as a C source that alone did not cause cytolysis. L55 Ab also had the ability to destroy HIV-1 particles via C-mediated lysis. By adding L55 Ab together with human C to mixed culture of HIV-infected cells and naive cells, HIV-1 replication was significantly suppressed, and this effect was synergistic when L55 Ab was combined with a reverse transcriptase inhibitor and a proteinase inhibitor. Therefore, a human IgM anti-GM2 mAb may be effective in treating HIV-infected patients, especially when used together with chemotherapeutic agents.

Anti-HIV Agents↗

Angioma serpiginosum: a report of 2 cases identified using epiluminescence microscopy.

BACKGROUND: Angioma serpiginosum is a rare, acquired vascular lesion simulating purpura, and should be differentiated from purpuric dermatoses such as Henoch-Schonlein purpura. OBSERVATIONS: We report 2 cases of angioma serpiginosum examined using epiluminescence microscopy. Characteristic findings of angiomas ("red lagoons") were observed entirely or focally in these 2 cases, but not in 4 cases of Henoch-Schonlein purpura and a case of senile purpura. CONCLUSION: Epiluminescence microscopy is beneficial in distinguishing angioma serpiginosum from purpuric dermatoses.

Adolescent↗

Presynaptic and postsynaptic dopaminergic binding densities in the nigrostriatal and mesocortical systems in early Parkinson's disease: a double-tracer positron emission tomography study.

To investigate changes in the relation between presynaptic and postsynaptic dopaminergic functions in vivo in both nigrostriatal and mesocortical systems in Parkinson's disease (PD), 10 drug-naive early PD patients were studied twice using positron emission tomography with [11C]CFT (dopamine transporter probe) followed by [11C]SCH 23390 (D1 receptor probe). Regional binding potentials (k3/k4) of [11C]CFT and [11C]SCH 23390 in the striatum (nigrostriatal system) and the orbitofrontal cortex (mesocortical system) were estimated by compartment analyses. Levels of [11C]CFT k3/k4 in the two projection areas were shown to be significantly lower in PD, whereas [11C]SCH 23390 levels remained unchanged. Regression analysis showed that estimates of CFT k3/k4 were positively correlated with those of SCH 23390 k3/k4 in the striatum in normal control, whereas the two binding estimates were less positively correlated in the caudate and inversely correlated in the putamen in PD. No significant correlation was observed in the orbitofrontal cortex in both groups. These results indicated that dopamine transporters and D1 receptors change in parallel in the normal striatal synapses, but the association becomes asymmetrical because of reduction in presynaptic and relative elevation in postsynaptic markers in PD. Alterations in synaptic parallel regulation in the nigrostriatal system might reflect early pathophysiology in the parkinsonian brain.

Aged↗

Tc-99m Technegas scintigraphy to evaluate the lung ventilation in patients with oral corticosteroid-dependent bronchial asthma.

Bronchial asthma is a clinical syndrome characterized by the reversibility of airway obstruction. Recently it has been suggested that remodeling of the airway causes irreversible airway obstruction which may be responsible for the patient's symptoms. With this background, the purpose of the present study was to assess patients with corticosteroid-dependent asthma by Tc-99m Technegas scintigraphy (Technegas) in both planar and SPECT images. Twelve patients (7 females and 5 males aged 36-72 years with a median age of 60 years: 4 smokers and 8 non-smokers) with oral corticosteroid-dependent asthma were enrolled in this study. Lung ventilation scanning with Technegas in both planar and SPECT images, high-resolution computed tomography, and pulmonary function tests were performed in all patients. The results of Technegas scanning were graded and correlations with other clinical parameters were evaluated. Significant abnormalities were detected by ventilation scintigraphy with Technegas in patients with corticosteroid-dependent bronchial asthma even during remission. Our data demonstrate that airflow obstruction took place in patients with corticosteroid-dependent asthma even during remission. Technegas scanning appears to be a useful radiopharmaceutical for demonstrating airflow obstruction in patients with bronchial asthma.

Adrenal Cortex Hormones↗