Biomedical subjects
T Kumamoto
Publications and source records attributed to T Kumamoto.
[Amphiphilic cationic drug myopathy, drug-induced lysosomal storage lipidosis].
Explore the source record for details and available documents.
[Myopathies in drug addicts].
Explore the source record for details and available documents.
[Fasciitis, perimyositis, microangiopathy].
Explore the source record for details and available documents.
Identification of a novel, dendritic cell-associated molecule, dectin-1, by subtractive cDNA cloning.
Dendritic cells (DC) are special subsets of antigen presenting cells characterized by their potent capacity to activate immunologically naive T cells. By subtracting the mRNAs expressed by the mouse epidermus-derived DC line XS52 with the mRNAs expressed by the J774 macrophage line, we identified five novel genes that were expressed selectively by this DC line. One of these genes encoded a type II membrane-integrated polypeptide of 244 amino acids containing a putative carbohydrate recognition domain motif at the COOH-terminal end. This molecule, termed "dectin-1," was expressed abundantly at both mRNA and protein levels by the XS52 DC line, but not by non-DC lines (including the J774 macrophage line). Dectin-1 mRNA was detected predominantly in spleen and thymus (by Northern blotting) and in skin-resident DC, i.e. Langerhans cells (by reverse transcription-polymerase chain reaction). Affinity-purified antibody against dectin-1 identified a 43-kDa glycoprotein in membrane fractions isolated from the XS52 DC line and from the dectin-1 cDNA-transfected COS-1 cells. His-tagged recombinant proteins containing the extracellular domains of dectin-1 showed marked and specific binding to the surface of T cells and promoted their proliferation in the presence of anti-CD3 monoclonal antibody at suboptimal concentrations. These in vitro results suggest that dectin-1 on DC may bind to as yet undefined ligand(s) on T cells, thereby delivering T cell co-stimulatory signals. Not only do these results document the efficacy of subtractive cDNA cloning for the identification of unique genes expressed by DC, they also provide a framework for studying the physiological function of dectin-1.
A novel mutation of the McLeod syndrome gene in a Japanese family.
McLeod syndrome is a rare X-linked hematologic and neuromuscular disorder manifested by chorea, myopathy, cardiomyopathy, areflexia, hyperCKemia, and acanthocytosis. Only four mutations have been reported in the gene responsible for McLeod syndrome. We report a novel gene mutation in a Japanese family. Direct sequencing of the PCR-amplified genomic DNA revealed the mutation was a single C-nucleotide insertion at codon 151 in exon 2 of the XK gene, which resulted in a 3'-frameshift. Study of family members revealed that the patient's mother was a manifesting carrier heterozygous for this mutation.
Neurogenic pulmonary edema induced by primary medullary hemorrhage: a case report.
We report a case of neurogenic pulmonary edema occurring in association with primary medullary hemorrhage. A pervious healthy 28-year-old man suddenly developed severe dyspnea without cardiac failure. Radiographs and computed tomography of the chest showed pulmonary edema. A diagnosis of primary medullary hemorrhage was made some weeks later by cranial magnetic resonance imaging showing an area of low signal intensity in both T1- and T2-weighted images in the right ventrolateral, medial, and dorsal medulla, extending from low to mid levels. We suspect that edema surrounding the lesion had superimposed an element of left dorsal medullary dysfunction and that bilateral dorsal medullary involvement had induced neurogenic pulmonary edema.
Increased lysosome-related proteins in the skeletal muscles of distal myopathy with rimmed vacuoles.
Investigators have speculated that the degenerative process in distal myopathy with rimmed vacuoles (DMRV) mainly involves the lysosomal system. To investigate possible protein abnormalities related to intracellular lysosomal proteolytic pathways in DMRV-affected muscles, we performed immunohistochemical analyses of certain proteins in muscle biopsy specimens obtained from patients with various neuromuscular diseases, including DMRV, muscular dystrophy, polymyositis, and amyotrophic lateral sclerosis, and in normal human muscles specimens. Immunohistochemically, most muscle fibers in normal control specimens showed little or no reaction for clathrin and alpha- and gamma-subunits of adaptin-constituted adaptin proteins (AP)-1 and AP-2, respectively. Abnormal increases in these proteins were demonstrated mainly in the cytoplasm of atrophic fibers or in necrotic fibers in all diseased specimens. Particularly in DMRV-affected muscles, alpha- and gamma-adaptins were often observed inside or on the rims of vacuoles and in the cytoplasm of vacuolated fibers. Abnormal increases in Golgi-zone protein were also demonstrated in DMRV muscles. The rims of rimmed vacuoles were negative for kinectin, an endoplasmic reticulum-binding protein. Positive staining for both proteins, however, was sometimes seen inside the vacuoles in DMRV-affected fibers. These results suggest increased endocytosis at the plasma membrane as well as secretion involving transport from the trans-Golgi network of the Golgi apparatus in DMRV. Accumulation of various lysosome-related proteins within the rimmed vacuoles indicates at least some of these vacuoles may be autolysosomes.
Posterior ventricular septal perforation in an 80-year-old man.
Ventricular septal perforation is a complication of acute myocardial infarction that is fatal unless treated surgically. Posterior ventricular septal perforation remains particularly difficult to repair successfully. We report an 80-year-old man with postinfarction posterior ventricular septal perforation who successfully underwent surgical repair using a technique similar to that described by Daggett et al. and was discharged in good health without postoperative septal shunt.
Proteasome expression in the skeletal muscles of patients with muscular dystrophy.
Previous investigators have suggested that proteolysis by calpain, a Ca2+-dependent protease, causes muscle fiber degradation in Duchenne and Becker muscular dystrophies (DMD/BMD). Recent evidence indicates that the nonlysosomal ATP-ubiquitin-dependent proteolytic complex (proteasomes) participates in muscle wasting during various catabolic states and in muscle fiber degradation in physiological or pathological conditions. To elucidate the possible role of proteasomes in dystrophic muscles, routine histochemistry and immunohistochemistry of 26S proteasomes were performed on muscle biopsy specimens obtained from patients with various neuromuscular disorders including DMD/BMD, polymyositis (PM), amyotrophic lateral sclerosis, and peripheral neuropathies, and on normal human muscle specimens. Immunohistochemically, proteasomes were located in the cytoplasm in normal human muscle, but their staining intensity was faint. Compared to control muscles, abnormal increases in both proteasomes and ubiquitin were demonstrated mainly in the cytoplasm of necrotic fibers and to a lesser extent in regenerative fibers in DMD/BMD and PM. Non-necrotic, atrophic fibers in all diseased muscles showed moderate or weak immunoreactions for the proteins; their staining intensities were stronger than those of control muscle fibers. Both proteins often colocalized well. Not all dystrophin-deficient muscle fibers showed a strong reaction for proteasomes. Our results showed increased proteasomes in necrotic and regenerative muscle fibers in DMD/ PMD, although this may not be disease-specific up-regulation. We suggest that the ATP-ubiquitin-dependent proteolytic pathway as well as the nonlysosomal calpain pathway may participate in muscle fiber degradation in muscular dystrophy.
Stroke after coronary artery bypass grafting in patients with cerebrovascular disease.
BACKGROUND: Stroke has been associated with a significantly increased mortality from coronary artery bypass grafting (CABG). To determine the predictors of stroke in patients undergoing CABG, we collected data on 472 consecutive patients. METHODS: From March 1991 to March 1999, all patients undergoing CABG at our institution underwent routine duplex scanning of the extracranial carotid and vertebral arteries. Seven patients with symptomatic carotid stenosis were treated by carotid endarterectomy (CEA) before CABG. RESULTS: There was a 10-fold increase in mortality (12.5%) associated with postoperative stroke. Many variables were analyzed by a multivariate technique and the severity of extracranial carotid artery stenosis was determined to be the only independent predictor of postoperative stroke (p < 0.01). None of the patients with carotid artery occlusion and none of the patients who underwent CEA before CABG experienced a stroke. CONCLUSIONS: To reduce the stroke rate, the indications for prophylactic CEA may be extended for asymptomatic patients with carotid artery stenosis greater than 75%.
Aortic arch repair using hypothermic circulatory arrest technique associated with pharmacological brain protection.
OBJECTIVE: Hypothermic circulatory arrest is a standard procedure for the treatment of aortic arch. However, there is a time limit for this procedure. There is now an urgent need to develop prophylactic measures to extend the time limit. We have used a pharmacological mixture of thiopental, nicardipine and mannitol for all patients undergoing circulatory arrest since 1991 to extend the safe limit. The purpose of this study was to analyze the neurological complications demonstrated by these patients and to evaluate the brain-protective effects of our measure. METHODS: The clinical records of 75 consecutive patients undergoing an aortic arch repair using a hypothermic circulatory arrest technique during the past 8 years were retrospectively reviewed. Systemic cooling was continued until a total disappearance of EEG activity. Prior to circulatory arrest, 15 or 30 mg/kg of thiopental, 20 mg of nicardipine and 300 ml of mannitol were infused into the venous reservoir of a cardiopulmonary bypass circuit. Graft replacement was performed in all patients and the extent of replacement was a total aortic arch in 43 patients, a distal aortic arch in 17, a hemiarch in 13 and a distal aortic arch and a total descending aorta in two. RESULTS: The duration of circulatory arrest ranged from 16 to 80 min (mean 41.5 min), and it exceeded 45 min in 37 patients. Operative mortality was 10.7% and two patients died of stroke. Three patients had permanent and three other patients had transient neural deficits. The incidence of stroke was 8.0% as a whole, and no correlation between the incidence of neurological complications and the duration of circulatory arrest was found. A multivariate analysis showed that the duration of circulatory arrest was determined as a predictor of neither operative mortality nor postoperative stroke. CONCLUSIONS: The findings of the present study suggest that our pharmacological brain protection appears to be effective for safely extending hypothermic circulatory arrest.
A new technique for closing a disrupted sternum.
Explore the source record for details and available documents.
Neurological abnormalities in cognitively impaired but not demented elderly.
OBJECTIVE: We determined the prevalence and clinical characteristics of elderly people with cognitively impaired but not demented (CIND) in the community. MATERIAL AND METHODS: We examined 945 elderly residents (aged 65 years or more) in a cross-sectional study of a standardized clinical examination in 27 randomly selected communities in the town of Mifune, a standard farming town in Japan. RESULTS: The prevalence of CIND and dementia were 10.8% and 4.8%, respectively, with both rates increasing with age. The frequency of most neurological signs in CIND elderly was greater than that found in subjects with no cognitive impairment (NCI) and less than that in subjects with dementia. The mean ADL disability score in CIND subjects also lay between the mean values for those with NCI and those with dementia. There were no differences in lifestyles between the CIND group and the other groups. CONCLUSION: The results suggest that a majority of CIND elderly suffer from brain dysfunction due to chronic neurological disorders or aging itself.
The reconstitution of CD45RBhiCD4+ naive T cells is inversely correlated with donor age in murine allogeneic haematopoietic stem cell transplantation.
A high incidence of opportunistic infections after unrelated bone marrow transplantation has been reported. Delayed lymphocyte recovery may be associated with opportunistic infections. Immune reconstitution is influenced by recipient age and graft-vs-host disease (GVHD). In fact, children develop GVHD less frequently than adults. However, the role of donor age is largely unknown. We examined the effect of donor age on lymphocyte reconstitution after transplant. Three-month-old BALB/c recipient mice were lethally irradiated and transplanted with allogeneic haematopoietic stem cells from A/J donor mice of different ages, ranging from 0 d to 12 months. The recovery of absolute lymphocyte counts and those of CD3+ T cells, CD4+ T cells and CD45RBhi CD4+ naive T cells in the early post-transplant period correlated inversely with donor age. Recipient mice transplanted with haematopoietic stem cells from younger donors showed significantly higher survival rates and mitogenic responses than adult donors. As T cells, especially CD4+ naive T cells, play an important role in host defence, faster recovery of CD4+ naive T cells in younger donors may contribute to reduced mortality in the early post-transplant period. The results suggest that it could be better to choose a younger donor if sufficient cell dose is available.
Results of a total aortic arch replacement for an acute aortic arch dissection.
OBJECTIVES: Recently, the immediate results of a surgical repair for an acute aortic arch dissection have dramatically improved. However, a total aortic arch replacement is recommended in a limited number of patients with an intimal tear located in the aortic arch. We have performed a total aortic arch replacement for all such patients with an acute aortic arch dissection since September 1995. METHODS: During the past 4 years, 27 consecutive patients who had an aortic arch dissection underwent a total aortic arch replacement. Twenty-five patients underwent an emergency operation. In 5 patients the intimal tear was located in the aortic arch, but in the rest of the patients, it was located in the ascending aorta or the proximal descending aorta. To obliterate any false channels, gelatin-resorcin-formol glue was used. RESULTS: The hospital mortality was 11%, and no cerebral complications were observed. Postoperative aortography and computed tomography showed no evidence of any persisting false channels in 15 patients (65%). During the follow-up period (ranging from 5 months to 4 years), two patients underwent a reoperation because of the recurrence of a dissection at the sinus of Valsalva. All patients, except for one who died after a reoperation, are still alive and free from any serious events at this writing. CONCLUSIONS: Resecting both the ascending and transverse aorta, irrespective of whether the intimal tear is located in the aortic arch, may be an acceptable alternative at experienced centers because of its low mortality and good midterm results.
[Should arterial grafts be used for urgent coronary artery bypass surgery?].
It is not clear whether arterial grafts should be used for emergency or urgent coronary artery bypass grafting (CABG) because harvest of internal thoracic arteries (ITAs) is not easy under urgent conditions and the blood flow through the ITAs may be inadequate immediately after CABG. The purpose of this study was to assess whether the use of arterial grafts in urgent CABG affects the outcome adversely or not. Twenty consecutive patients who underwent urgent CABG within 48 hours following coronary angiography at our institute between July 1991 and October 1998 were reviewed. The patients who underwent CABG with associated procedures were excluded. Among these subjects, 11 patients received at least one arterial graft. Only 1 patient died of subarachnoidal hemorrhage, and the hospital mortality rate was 5.0%. According to the overall survival rate, cardiac-death-free rate, and cardiac-event-free rate, the long-term outcome was much better in the patients with arterial grafts than those with saphenous vein grafts alone. We suggest that arterial grafts should be used even for urgent CABGs since the use of arterial grafts may not affect operative results adversely and will confer better long-term benefits.
A case of sarcoidosis presenting as multiple pulmonary nodules, nasopharyngeal and cerebellopontine tumors.
A 64-year-old woman presented with multiple pulmonary nodules, and after spontaneous regression of the pulmonary lesions in six months, nasopharyngeal and right cerebellopontine tumors developed. Noncaseous epithelioid cell granulomas were demonstrated histologically in both resected pulmonary and nasopharyngeal tumors. She complained of hearing loss and tinnitus probably due to the cerebellopontine tumors. Corticosteroid therapy resulted in the improvement of these symptoms and the gradual decrease of tumor size. Although histological probe of the cerebellopontine tumors was not diagnostic, this patient was finally diagnosed as having sarcoidosis, based on the clinicopathological features, including systemic granulomatous lesions, MRI findings, and good response to corticosteroid therapy. The diagnosis of sarcoidosis is sometimes difficult when its clinical manifestations are uncommon.