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Biomedical subjects

Toshiaki Hanafusa

Publications and source records attributed to Toshiaki Hanafusa.

At least 37 records · Page 2Linked to original sources

[Septic shock induced by Serratia marcescens complicating adult T-cell leukemia (ATL)].

A 75-year-old woman was admitted with fever of unknown origin and liver damage, and treated with prednisolone. Hypercalcemia appeared when of the dose of prednisolone was reduced, and human T-cell lymphotropic virus type-I (HTLV-I) proviral DNA was detected in the leukemic cells by Southern blot analysis, and a diagnosis of acute adult T-cell lymphoma (ATL) was made. After chemotherapy with sobuzoxane was started, she went into septic shock caused by multiple resistant Serratia marcesense, and was treated with PMX-DHP and antibiotics. Although ner general condition and her serum cytokine leyels improved, the septic shock became more severe, and the patient died. Serratia marcesense expreses lipopolysaccharide (LPS), a biologically active substance that is present in gram-negative bacteria. Exposure to LPS leads to activation of cytokines, including TNF-alpha, IL-1beta, IL-6, and IFN-gamma. After treatment with PMX-DHP, the patient's general condition improved, but she died of septic shock. Bacterial infection may be a life-threatening complication in the immunocompromised hosts and elderly patients, particularly when granulocytopenia has been induced by chemotherapy, and thus such these patients require careful management.

Aged↗

Location of out-of-hospital cardiac arrests in Takatsuki City: where should automated external defibrillator be placed.

BACKGROUND: Public access defibrillation has been introduced to improve the outcome of patients experiencing out-of-hospital cardiac arrest (OHCA). The aim of this study was to examine the best location for automated external defibrillators (AED). METHODS AND RESULTS: All patients who were resuscitated after OHCA by emergency medical technicians in Takatsuki City over 6 years were enrolled. The annual incidence of OHCA and the number of 1-year survivors with good neurological outcome in each of 21 sub-location categories were investigated, as well as the ratio of ventricular fibrillation (VF) as the initial rhythm to the total OHCA in each of 5 location categories. In total, there were 1,112 patients with OHCA, 62 (5.6%) with VF and 14 (1.3%) with good neurological outcome. The annual incidence of cardiac arrest (CA) per site was the highest in railway stations (0.3000), followed by hospitals (0.1802), homes for the aged (0.1115), playgrounds (0.0769) and golf courses (0.0667). However, none of the patients experiencing CA at railway stations, homes for the aged and golf courses had a good neurological outcome. The ratio of VF to total CA was the highest in the workplace (35.3%). CONCLUSIONS: The 6 locations, including workplace, are recommended as appropriate locations for AED.

Catchment Area, Health↗

Hypertensive brainstem encephalopathy without parieto-occipital lesion--two case reports.

Two patients presented with malignant hypertension associated with encephalopathy predominantly manifesting as brainstem lesion. T(2)-weighted and fluid-attenuated inversion recovery magnetic resonance (MR) imaging revealed diffuse hyperintense areas in the pons and scattered lesions in the cerebellum, basal ganglia, and cerebral subcortex without parieto-occipital lesions. Diffusion-weighted MR imaging demonstrated these lesions as normal intensity, indicating vasogenic edema. These lesions resolved rapidly once hypertension was controlled. Review of clinical findings for 14 other patients with hypertensive brainstem encephalopathy without parieto-occipital lesions suggested that anterior circulation structures supplied by the carotid artery are frequently involved in such patients.

Adult↗

[Sick-day management in elderly patients with diabetes mellitus].

Sick-day is defined as a state of common illness like cold or flu, which can reduce oral intake and make blood sugars hard to control in diabetic patients. The symptoms associated with hyper- or hypoglycemia may be atypical in the geriatric population, therefore, elderly patients need to take extra precautions on sick days to avoid diabetic crises. The elderly are particularly vulnerable to hyperglycemia and dehydration, the key components of hyperosmolar hyperglycemic syndrome, because insulin sensitivity and thirst mechanisms decrease with increasing age. Frequent monitoring of blood glucose is recommended and an individualized sick-day plan in considering the heterogeneity of older patients is important.

Aged↗

[Effective measurement of coronary flow velocity reserve (CFVR) with transthoracic Doppler echocardiography (TTDE) for plasma cell leukemia with hyperviscosity syndrome].

A 67-year-old woman was admitted with impaired general performance, suffering from fatigue, chest oppression on exertion, and paresthesia of the finger trips. The laboratory findings showed increased white blood cells with abnormal cells, and serum immunofixation test showed monoclonal IgM kappa paraprotein. On flow cytometric immunophenotyping with CD38 gating, most of the abnormal cells expressed surface CD20, CD138, cytoplasmic IgM, but neither surface CD56 nor surface IgM. Immunohistochemical staining of abnormal cells was positive for surface CD38, surface CD20 and cytoplasmic IgM. The final diagnosis was plasma cell leukemia IgM kappa type. Electrocardiography (ECG) on admission showed ST depression in II, III, aV(F), V4, V5, and V6. Coronary angiography (CAG) is invasive and difficult for patients with renal failure, therefore the patient underwent transthoracic Doppler echocardiography (TTDE), which revealed reduced coronary flow velocity reserve (CFVR). Two courses of VAD therapy were administered, then the condition improved, the serum IgM level decreased, abnormal cells were decreased in peripheral blood and bone marrow aspirates, and the creatinine levels improved. With the return of normal ECG findings and improved CFVR, the abnormal ECG and reduction in CFVR was thought to be associated with the hyperviscosity syndrome in PCL. Noninvasive assessment of CFVR by TTDE is significantly useful for the patients who have renal failure and need chemotherapy.

Aged↗

[Acute pancreatitis during the treatment of relapsed acute promyelocytic leukemia with As2O3].

A 77-year-old man suffered from acute pancreatitis during the treatment of relapsed acute promyelocytic leukemia with As2O3. He presented with epigastralgia on day 25 during the treatment with As2O3. Pancreatic enzyme levels were elevated and the computed tomography scan of the abdomen showed swelling of the pancreas. As acute pancreatitis due to As2O3 was suspected, As2O3 was discontinued. Intravenous gabexate mesilate was administered, and the pancreatitis improved. Acute pancreatitis should be considered as a possible complication during treatment with As2O3.

Acute Disease↗

[A case of bullous pemphigoid associated with Pneumocystis pneumonia and Cytomegalovirus pneumonia].

A 68-year-old man was admitted to our hospital presenting cutaneous pruritic lesions consisting of tense blisters with serous content on his arms and legs. Histological findings of skin biopsy confirmed a diagnosis of bullous pemphigoid in March 2005. After 10 weeks of prednisone therapy for bullous pemphigoid, he presented with increasing breathlessness and high fever. He was admitted to our hospital because of severe hypoxemia on May 29, 2005, and mechanical ventilation was started from the first hospital day. Chest computed tomography showed marked ground-glass opacities in both lungs. The levels of beta-D glucan and KL-6 in his sera were elevated. We suspected Pneumocystis pneumonia and Cytomegalovirus pneumonia. Under mechanical ventilation, he received steroid pulse therapy, and sulfamethoxazole-trimethoprim and ganciclovir. A polymerase chain reaction assay of bronchoalveolar lavage fluid showed Pneumocysitis DNA and Cytomegalovirus DNA. On the 12th hospital day, he was weaned from mechanical ventilation. Follow-up chest computed tomography showed marked resolution of diffuse ground-glass opacity in both lungs. We need to consider the development of Pneumocystis pneumonia and Cytomegalovirus pneumonia during steroid therapy for bullous pemphigoid.

Aged↗

Role for IL-4 nonproducing NKT cells in CC-chemokine ligand 2-induced Th2 cell generation.

NKT cells from C57Bl/6 mice are known to be the initial cellular source of IL-4 that acts as a trigger for Th2 cell differentiation. CC-chemokine ligand 2 (CCL2) has been described as an initial stimulator of IL-4 production by these cells; however, IL-4 was not produced by NKT cells from BALB/c mice even when Th2 cell responses were established in these mice. In this study, we found a new pathway for CCL2-associated Th2 cell generation in BALB/c mice. Splenic T cells from BALB/c mice produced IL-4 in response to CCL2 stimulation. However, IL-4 production was not seen in cultures of splenic T cells from CD1-/- mice (BALB/c origin), whereas, in the presence of CCL2, splenic T cells from CD1-/- mice produced IL-4 when NKT cells from wild-type mice were added. CCL2 induced IL-4 in cultures of NKT cells cocultured with naive T cells, but IL-4 was not produced by these cells cultured separately with CCL2. Interestingly, IL-4 was produced by naive T cells cocultured with NKT cells that were previously treated with CCL2 (CCL2-NKT cells). In addition, IL-4 was produced by naive T cells supplemented with a culture supernatant of CCL2-NKT cells. These results indicate that, through the production of a soluble factor(s) other than IL-4, NKT cells play a role in the CCL2-associated generation of Th2 cells.

Animals↗

Cell shrinkage evoked by Ca2+-free solution in rat alveolar type II cells: Ca2+ regulation of Na+-H+ exchange.

The effects of intracellular Ca2+ concentration, [Ca2+]i, on the volume of rat alveolar type II cells (AT-II cells) were examined. Perfusion with a Ca2+-free solution induced shrinkage of the AT-II cell volume in the absence or presence of amiloride (1 microm, an inhibitor of Na+ channels); however, it did not in the presence of 5-(N-methyl-N-isobutyl)-amiloride (MIA, an inhibitor of Na+-H+ exchange). MIA decreased the volume of AT-II cells. Inhibitors of Cl(-)-HCO3- exchange, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) also decreased the volume of AT-II cells. This indicates that the cell shrinkage induced by a Ca2+-free solution is caused by a decrease in NaCl influx via Na+-H+ exchange and Cl(-)-HCO3- exchange. Addition of ionomycin (1 microm), in contrast, induced cell swelling when AT-II cells were pretreated with quinine and amiloride. This swelling of the AT-II cells is not detected in the presence of MIA. Intracellular pH (pHi) measurements demonstrated that the Ca2+-free solution or MIA decreases pHi, and that ionomycin increases it. Ionomycin stimulated the pHi recovery after an acid loading (NH4+ pulse method), which was not noted in MIA-treated AT-II cells. Ionomycin increased [Ca2+]i in fura-2-loaded AT-II cells. In conclusion, the Na+-H+ exchange activities of AT-II cells, which maintain the volume and pHi, are regulated by [Ca2+]i.

Animals↗

Role of natural killer T (NKT) cells lacking interleukin (IL)-4 producing abilities on the CC-chemokine ligand 2-associated herpes simplex virus type 1 infection in human severe combined immunodeficiency (SCID) mouse chimeras.

CC-chemokine ligand 2 (CCL2/monocyte chemoattractant protein 1) is known to have an important role on T helper type 2 (Th2) cell generation and described to induce interleukin (IL)-4 production by activated T cells. In the present study, an increase of CCL2 production in cultures of peripheral blood lymphocytes (PBL) from patients with severe thermal injuries was demonstrated. Severe combined immunodeficiency (SCID) mice reconstituted with PBL from healthy donors (PBL-SCID chimeras) were resistant to infection with herpes simplex virus type 1 (HSV-1). Treatment of these chimeras with recombinant human CCL2 resulted in an increased susceptibility to the same HSV-1 infection. However, human SCID mouse chimeras created by PBL depleted of natural killer T (NKT) cells (NKT(-) PBL-SCID chimeras) were resistant to HSV-1 infection, even though they were treated with CCL2. IL-4 was not detected in the sera of NKT(-) PBL-SCID chimeras treated with CCL2, while IL-4 was detected in the sera of PBL-SCID chimeras under the same CCL2 administration. NKT cells isolated from PBL were shown to be cells not responsible for CCL2-stimulated IL-4 production. However, in the presence of CCL2, IL-4 was detected in culture fluids of NKT cells co-cultured with naive T cells. This cytokine was produced in co-cultures of NKT cells pretreated with CCL2 (CCL2-NKT cells) and naive T cells. In addition, IL-4 production was demonstrated in transwell cultures of CCL2-NKT cells and naive T cells. These results suggest that NKT cells lacking IL-4 producing abilities contribute to the CCL2-associated increase in the susceptibility of thermally injured patients to HSV-1 infection through the induction of Th2 cell generation.

Animals↗

Pulmonary parenchymal infiltrates in a patient with CD20-positive multiple myeloma.

A 53-yr-old woman developed a dry cough after the completion of multi-agent chemotherapy. The biopsy specimens showed diffuse infiltrates with multiple myeloma (MM) cells. Immunohistochemistry revealed positive staining in MM cells with surface CD20, surface CD38, and cytoplasmic IgG. This report represents the first reported case of pulmonary parenchymal infiltrates in a patient with CD20-positive MM.

ADP-ribosyl Cyclase↗

Simple and useful tests for discriminating between acute aortic dissection of the ascending aorta and acute myocardial infarction in the emergency setting.

BACKGROUND: It is important to rapidly distinguish patients with acute aortic dissection of the ascending aorta (AADa) from those with acute myocardial infarction (AMI), because minimizing the time to initiation of reperfusion therapy leads to maximum benefits for AMI and erroneous reperfusion therapy for AADa can produce harmful outcomes. The aim of this study was to find a simple test to distinguish such patients. METHODS AND RESULTS: Data were collected from 29 consecutive patients with AADa and 49 consecutive patients with AMI who were admitted within 4 h of the onset of symptoms. The D-dimer concentration and the ratio of the maximum upper mediastinal diameter to the maximum thoracic diameter on plain chest radiograph (M-ratio) in the emergency room were studied retrospectively. Setting the cutoff values of the D-dimer concentration and the M-ratio to 0.8 or 0.9 microg/ml and 0.309, respectively, gave a sensitivity of 93.1% and 93.1% for AADa, respectively, and a sensitivity of 91.8% and 85.7% for AMI, respectively. CONCLUSIONS: The D-dimer value and the M-ratio, with appropriate cutoff values, have potential as tests that can be routinely used to exclude AADa patients from patients diagnosed with AMI prior to reperfusion therapy.

Aged↗

Serum heart-type fatty acid-binding protein concentration positively correlates with the length of aortic dissection.

BACKGROUND: Patients with aortic dissection (AD) often demonstrate positive heart-type fatty acid-binding protein (H-FABP), but its significance is unclear. METHODS AND RESULTS: In 63 of 64 consecutive AD patients, the serum H-FABP concentration was measured and the H-FABP positive rate calculated (cutoff value: 6.2 ng/ml) for each of following factors: (1) with or without dissection of the ascending aorta; and (2) a thrombosed false lumen; (3) length score; (4) presence of shock; (5) malperfusion of limbs; (6) ST elevation and/or depression on electrocardiogram; and (7) renal dysfunction. In total 36 AD patients had a positive H-FABP test. Statistically significant differences in the H-FABP positive rate were observed between those with and without ascending AD (76.7% vs 39.4%, p = 0.003), and in the length score (p < 0.001). Multivariate logistic regression test demonstrated that the most significant factor was the length score (odds ratio: 2.239 (95% confidence interval: 1.119-4.481), p = 0.023). Moreover, a significant correlation was observed between length score and absolute H-FABP value (r = 0.420, p = 0.001). CONCLUSIONS: In patients with AD, an increased serum H-FABP concentration is caused by the protein being released not only from the cardiac muscle but also from skeletal muscle, or possibly the aortic wall. Physicians using H-FABP for detection of myocardial injury need to be aware that patients with a long or ascending AD will show an elevation of H-FABP.

Adult↗

Flow cytometric immunophenotyping of adult T-cell leukemia/lymphoma using CD3 gating.

Adult T-cell leukemia/lymphoma (ATLL) is a lymphoproliferative neoplasm of helper T lymphocytes caused by human T-cell leukemia virus type-1 (HTLV-1). The disease was first described in Kyushu, in southwestern Japan, and most frequently occurs in endemic areas, such as Japan, the Caribbean basin, West Africa, Brazil, and northern Iran. ATLL is essentially a disease of adults, characterized clinically by generalized lymphadenopathy, hepatosplenomegaly, skin lesions, and hypercalcemia. The prognosis of most patients is quite poor, with a median survival time of only 13 months, even if multiagent combination chemotherapy is given. In the present study, flow cytometric immunophenotyping with CD3 gating was performed on 30 samples from 26 patients who had been given a diagnosis of ATLL. The records of these patients also were reviewed retrospectively. In 14 of the 30 samples, an abnormal CD3(low) T-cell population was distinguishable from the normal T-cell populations by flow cytometric analysis. Herein we report a novel strategy for flow cytometric immunophenotyping of ATLL facilitated by CD3(low) gating.

Adult↗

Re-entry circuit in ventricular tachycardia due to focal fatty-fibrosis in a patient with myotonic dystrophy.

A 69-year-old man with a recurrent ventricular tachycardia (VT) was admitted. The patient was diagnosed as myotonic dystrophy type 1 (DM1) and DNA analysis revealed 1,800 CTG-repeat expansion in the myotonic dystrophy protein kinase (DMPK) gene. Ultrasonic cardiogram (UCG), left ventriculogram (LVG) and magnetic resonance imaging (MRI) did not show any abnormal sign including fatty infiltration. But, endomyocardial biopsy obtained from ventricular outflow tract revealed severe fatty infiltration and interstitial fibrosis. Radiofrequency catheter ablation at the biopsy site could eliminate VT, so it was strongly suggested that the re-entry circuit was formed by focal fatty-fibrosis. Careful observation should be continued for a long period.

Adipose Tissue↗

[A case of interstitial pneumonia associated with dermatomyositis effectively treated with cyclosporin-A and cyclophosphamide pulse].

A 46-year-old male demonstrated edematous fingers on both hands in November 2003, and interstitial pneumonia was noted on chest X-ray during a medical check-up in December 2003. Since muscular weakness and fever developed thereafter, and interstitial pneumonia was aggravated on chest X-ray and CT, the patient was admitted to our hospital on March 25, 2004. Heliotrope-like erythema, and Gottron's sign were noted. Laboratory findings showed the following ; LDH 876 U/l ; CK 224 U/l ; CRP 5.68 mg/dl ; and KL-6 3270 U/ml. Autoantibodies such as anti-Jo-1 antibody were all negative. Chest X-ray and CT showed ground-glass opacity in the bilateral lower dorsal regions of the lung, and reduced volume of the inferior lobe. He was diagnosed as having dermatomyositis (DM) associated with progressive interstitial pneumonia. Although a combination of steroid pulse therapy and Cyclosporin-A were administered, the pulmonary lesions became aggravated. Additional intravenous Cyclophosphamide (IVCY) was initiated on the 6th hospital day, and interstitial pneumonia was markedly improved. Cases of progressive interstitial pneumonia associated with DM that are negative for anti-Jo-1 antibody and show a low ratio of CK/LDH are resistant to various treatments. Our case suggested that combination therapy with steroid, Cyclosporin-A, and IVCY is useful for the treatment of progressive interstitial pneumonia with DM.

Cyclophosphamide↗