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Biomedical subjects

C Hashimoto

Publications and source records attributed to C Hashimoto.

At least 19 recordsLinked to original sources
PubMed2005

Human herpesvirus-6 encephalitis after unrelated cord blood transplantation.

Here we describe 2 patients with acute leukemia in whom human herpesvirus-6 (HHV-6) encephalitis developed after cord blood transplantation. In patients 1 and 2, generalized seizure and coma developed on day 62 and day 15, respectively, after cord blood transplantation, which failed to engraft in patient 1. Magnetic resonance imaging (MRI) of patient 1's brain showed low-intensity signals at the gyri of the bilateral lateral lobes on T1-weighted images and high-intensity signals on T2-weighted images. MRI of patient 2's brain showed high-intensity signals in bilateral white matter on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. Cerebrospinal fluid examination revealed an increased protein level with pleocytosis in patient 1 and a normal protein level without pleocytosis in patient 2. Polymerase chain reaction analysis detected HHV-6 DNA in the cerebrospinal fluid of both patients. Patient 1 recovered after administration of gancyclovir for 3 weeks. However, she again suffered from encephalitis after discontinuation of gancyclovir, and died of sepsis. Patient 2 died from an anoxic brain caused by generalized seizure. When neurological symptoms and signs appear in hematopoietic stem cell transplantation recipients, we should consider HHV-6 encephalitis and promptly and empirically treat them with gancyclovir or foscarnet.

Adult↗
PubMed2004

Transport of solar wind into Earth's magnetosphere through rolled-up Kelvin-Helmholtz vortices.

Establishing the mechanisms by which the solar wind enters Earth's magnetosphere is one of the biggest goals of magnetospheric physics, as it forms the basis of space weather phenomena such as magnetic storms and aurorae. It is generally believed that magnetic reconnection is the dominant process, especially during southward solar-wind magnetic field conditions when the solar-wind and geomagnetic fields are antiparallel at the low-latitude magnetopause. But the plasma content in the outer magnetosphere increases during northward solar-wind magnetic field conditions, contrary to expectation if reconnection is dominant. Here we show that during northward solar-wind magnetic field conditions-in the absence of active reconnection at low latitudes-there is a solar-wind transport mechanism associated with the nonlinear phase of the Kelvin-Helmholtz instability. This can supply plasma sources for various space weather phenomena.

Journal Article↗
PubMed2004

Acrogeria (Gottron type): a vascular disorder?

We report a 27-year-old Japanese man with the peculiar clinical features of acrogeria. He had had perniosis since early childhood. Prominent atrophic skin changes over the hands, hallux valgus, shortened distal phalanges and atrophic scars on his auricles were noted. X-ray of the hands revealed acro-osteolytic changes of the distal phalanges, and arteriography demonstrated multiple occluded branches of the digital arteries. There were no histological changes of systemic sclerosis in his forearm skin, nor antinuclear antibodies or coagulation disorders. Western immunoblotting demonstrated decreased production of type III collagen by dermal fibroblasts both from an affected finger and from the unaffected upper arm. Although the pathogenesis of acrogeria is unknown, the present case suggests that peripheral circulatory disturbance, as well as a congenital abnormality in type III collagen synthesis, may partly account for the pathogenesis of Gottron-type acrogeria.

Adult↗
PubMed2002

Yersinia pseudotuberculosis infection in breeding monkeys: detection and analysis of strain diversity by PCR.

In the last three decades, several monkeys reared in outdoor/indoor-outdoor breeding colonies and cages of the Primate Research Institute, Kyoto University, died of yersiniosis caused by Yersinia pseudotuberculosis, necessitating introduction of a method to detect the bacteria rapidly and thus allow preventive measures to be undertaken. A rapid nested polymerase chain reaction (PCR) method for identification of Y. pseudotuberculosis in fecal samples and a random amplified polymorphic DNA (RAPD)-PCR approach for distinguishing between bacterial strains were therefore developed. Yersinia pseudotuberculosis isolates from monkey specimens were found to be classifiable into several types. To determine the source of infection, hundreds of fecal samples of wild rats, pigeons, and sparrows were collected from around the breeding colonies and cages, and subjected to PCR analyses. Yersinia pseudotuberculosis was detected in 1.7% of the fecal samples of wild rats. The DNA fingerprints of the bacteria revealed by RAPD-PCR were the same as that of one strain isolated from macaques, suggesting the wild rat to be a possible source of infection.

Adhesins, Bacterial↗
PubMed2001

Activation of a protease cascade involved in patterning the Drosophila embryo.

Dorsoventral patterning of the Drosophila embryo is initiated by a ventralizing signal. Production of this signal requires the serine proteases Gastrulation Defective (GD), Snake, and Easter, which genetic studies suggest act sequentially in a cascade that is activated locally in response to a ventral cue provided by the pipe gene. Here, we demonstrate biochemically that GD activates Snake, which in turn activates Easter. We also provide evidence that GD zymogen cleavage is important for triggering this cascade but is not spatially localized by pipe. Our results suggest that a broadly, rather than locally, activated protease cascade produces the ventralizing signal, so a distinct downstream step in this cascade must be spatially regulated to restrict signaling to the ventral side of the embryo.

Animals↗
PubMed2001

Teaching continuous curvilinear capsulorhexis using a postmortem pig eye with simulated cataract(2)(2).

We modified an inexpensive, easily prepared model using a postmortem pig eye for training ophthalmology residents to perform continuous curvilinear capsulorhexis. To reduce the tension and elasticity of the porcine anterior lens capsule, 0.05 mL of formalin mixed with hydroxyethylcellulose or a viscoelastic material is injected into the anterior chamber via the corneal limbus to fix the surface of the central anterior lens capsule of the pig eye in situ. One or 2 minutes after the injection, only the anterior lens capsule is fixed and corneal transparency is maintained. The reduction in tension and elasticity of the anterior lens capsule caused by its fixation increases the resemblance of the simulated cataract to the human cataract.

Animals↗
PubMed2000

Gastrulation defective is a serine protease involved in activating the receptor toll to polarize the Drosophila embryo.

The dorsoventral axis of the Drosophila embryo is induced by a ventrally restricted ligand for the receptor Toll. The Toll ligand is generated by a proteolytic processing reaction, which occurs at the end of a proteolytic cascade and requires the gastrulation defective (gd), nudel, pipe, and windbeutel genes. Here we demonstrate that the GD protein is a serine protease and that the three other genes act to restrict GD activity to the ventral side of the embryo. Our data support a model in which the GD protease catalyzes the ventral activation of the proteolytic cascade that produces the Toll ligand.

Amino Acid Sequence↗
PubMed2000

A novel Drosophila serpin that inhibits serine proteases.

Serpins define a large protein family in which most members function as serine protease inhibitors. Here we report the results of a search for serpins in Drosophila melanogaster that are potentially required for oogenesis or embryogenesis. We cloned and sequenced ovarian cDNAs that encode six distinct proteins having extensive sequence similarity to mammalian serpins, including residues important in the serpin inhibition mechanism. One of these new serpins in recombinant form inactivates, and complexes with, trypsin-like proteases in vitro. To our knowledge, these results represent the first evidence for a serpin in Drosophila that functions as a serine protease inhibitor.

Amino Acid Sequence↗
PubMed2000

The nudel protease of Drosophila is required for eggshell biogenesis in addition to embryonic patterning.

The dorsoventral axis of the Drosophila embryo is defined by a ventral signal that arises within the perivitelline space, an extracellular compartment between the embryo plasma membrane and the vitelline membrane layer of the eggshell. Production of the ventral signal requires four members of the serine protease family, including a large modular protein with a protease domain encoded by the nudel gene. Here we provide evidence that the Nudel protease has an integral role in eggshell biogenesis. Mutations in nudel that disrupt Nudel protease function produce eggs having vitelline membranes that are abnormally permeable to the dye neutral red. Permeability varies among mutant nudel alleles but correlates with levels of Nudel protease catalytic activity and function in embryonic dorsoventral patterning. These mutations also block cross-linking of vitelline membrane proteins that normally occurs upon egg activation, just prior to fertilization. In addition, Nudel protease autoactivation temporally coincides with vitelline membrane cross-linking and can be triggered in mature eggs in vitro by conditions that lead to egg activation. We discuss how the Nudel protease might be involved in both eggshell biogenesis and embryonic patterning.

Animals↗
PubMed2000

Biochemical defects of mutant nudel alleles causing early developmental arrest or dorsalization of the Drosophila embryo.

The nudel gene of Drosophila is maternally required both for structural integrity of the egg and for dorsoventral patterning of the embryo. It encodes a structurally modular protein that is secreted by ovarian follicle cells. Genetic and molecular studies have suggested that the Nudel protein is also functionally modular, with a serine protease domain that is specifically required for ventral development. Here we describe biochemical and immunolocalization studies that provide insight into the molecular basis for the distinct phenotypes produced by nudel mutations and for the interactions between these alleles. Mutations causing loss of embryonic dorsoventral polarity result in a failure to activate the protease domain of Nudel. Our analyses support previous findings that catalytic activity of the protease domain is required for dorsoventral patterning and that the Nudel protease is auto-activated and reveal an important role for a region adjacent to the protease domain in Nudel protease function. Mutations causing egg fragility and early embryonic arrest result in a significant decrease in extracellular Nudel protein, due to defects in post-translational processing, stability, or secretion. On the basis of these and other studies of serine proteases, we suggest potential mechanisms for the complementary and antagonistic interactions between the nudel alleles.

Alleles↗
PubMed2000

[Idiopathic mediastinal and subcutaneous emphysema in a patient with acute lymphocytic leukemia after allogeneic bone marrow transplantation].

A 45-year-old man was diagnosed as having Ph1+ acute lymphocytic leukemia (ALL) in February 1997. Complete remission was achieved by chemotherapy. Allogeneic BMT from his HLA-identical sister was performed on June 11, 1997. Engraftment was relatively quick, but acute GVHD (grade I) developed. The patient was discharged on day 113. Seven months after BMT, in January 1998, exertional dyspnea developed gradually. Chest X-ray examination showed diffuse interstitial pneumonia, for which corticosteroid was started immediately. The symptoms and signs gradually improved. However, on the 20th hospital day (February 23), bilateral subcutaneous emphysema developed in the neck and supraclavicular region. Chest X-ray and CT examinations showed pneumomediastinum without pneumothorax. The pneumomediastinum and subcutaneous emphysema gradually subsided after 3 weeks of bed rest. Subcutaneous emphysema and pneumomediastinum are relatively rare complications of allogeneic BMT.

Bone Marrow Transplantation↗
PubMed2000

[Successful allogeneic bone marrow transplantation following fungal liver abscess treatment in a patient with chronic myeloid leukemia in blastic crisis].

A 40-year-old man was diagnosed as having chronic myeloid leukemia (CML) in December 1990 and received busulfan and hydroxyurea. He developed myeloid blast crisis in February 1996. After DCMP combination chemotherapy, his disease reverted to chronic phase, but right hypochondrial pain developed and low-grade fever persisted. Abdominal CT scan revealed multiple low-density areas in the liver, suggestive of abscess formation. Grocott staining of a liver biopsy sample revealed granuloma and fungus. The patient was treated with intravenous amphotericin B (AMPH-B) without success. AMPH-B was then administered via a catheter placed in the portal vein on January 6, 1997, and an additional catheter placed in the hepatic artery on March 28. AMPH-B was administered through both catheters for more than two months, but later substituted by fluconazole because of renal impairment. On September 10, allogeneic bone marrow transplantation from the patient's HLA-identical brother was performed, despite persistence of the abnormal CT findings. Acute grade III GVHD developed, but there was no evidence of reactivation of the liver abscesses. This case demonstrates that a prior fungal liver abscess is not an absolute contraindication for BMT if prophylactic antifungal drugs are administered and careful observation is conducted.

Adult↗
PubMed1999

Signal transduction by a protease cascade.

The dorsoventral axis of the Drosophila embryo is determined by a spatial cue generated by ovarian somatic cells. This cue is communicated to the embryo through an extracellular serine protease cascade active only on the ventral side of the embryo. Studies of the proteases and somatically expressed proteins involved in this signalling process suggest a working model for how the protease cascade is locally activated hours after the ovarian somatic cells have degenerated.

Animals↗
PubMed1999

Long-term liver function of recipients with hepatitis G virus infection after bone marrow transplantation.

To clarify the role of hepatitis G virus (HGV) infection in liver dysfunction following allogeneic BMT, we examined cryopreserved serum samples from 33 patients who had a history of blood transfusions before BMT and whose serum samples had been stored periodically, before BMT, on day 100, and thereafter for the presence of HGV-RNA and hepatitis C virus (HCV)-RNA by reverse transcription polymerase chain reaction. Nineteen patients (58%) out of 33 were positive for HGV-RNA before BMT and 10 for HCV-RNA. All patients positive for HCV-RNA were also positive for HGV-RNA. Patients were divided into three groups according to their viral status before BMT; namely, the G+C+ group (n = 10), the G+C- group (n = 9) and the G-C- group (n = 14). Two patients in the G-C- group became positive for HGV-RNA after BMT. One patient in the G+C- group suffered an acute exacerbation of hepatitis, with GPT levels reaching over 1000 IU/l, 2 and 3 years after BMT, showing quite a different clinical course from those in the G+C- group. Excluding these three patients, GPT levels of the patients in the G+C+ group were significantly higher after day 100 and remained higher than those of patients in the G+C- and G-C- groups for at least 4 years. There were no significant differences in post-transplant GPT levels between the G+C- group and the G-C- group at any time point. Of the seven patients followed-up for 5 to 10 years, three patients became HGV-RNA-negative, while four remained positive. In the absence of HCV co-infection, the behavior of GPT values post transplant in patients with HGV infection did not differ from those without HGV infection. With respect to the patient who was G+C- and showed high values of GPT 2 and 3 years post transplant, we suspect that his liver dysfunction might have been caused by some unknown virus or etiology.

Adolescent↗
PubMed1999

Involvement of the small GTPases XRhoA and XRnd1 in cell adhesion and head formation in early Xenopus development.

The Rho family of small GTPases regulates a variety of cellular functions, including the dynamics of the actin cytoskeleton, cell adhesion, transcription, cell growth and membrane trafficking. We have isolated the first Xenopus homologs of the Rho-like GTPases RhoA and Rnd1 and examined their potential roles in early Xenopus development. We found that Xenopus Rnd1 (XRnd1) is expressed in tissues undergoing extensive morphogenetic changes, such as marginal zone cells involuting through the blastopore, somitogenic mesoderm during somite formation and neural crest cells. XRnd1 also causes a severe loss of cell adhesion in overexpression experiments. These data and the expression pattern suggest that XRnd1 regulates morphogenetic movements by modulating cell adhesion in early embryos. Xenopus RhoA (XRhoA) is a potential XRnd1 antagonist, since overexpression of XRhoA increases cell adhesion in the embryo and reverses the disruption of cell adhesion caused by XRnd1. In addition to the potential roles of XRnd1 and XRhoA in the regulation of cell adhesion, we find a role for XRhoA in axis formation. When coinjected with dominant-negative BMP receptor (tBR) in the ventral side of the embryo, XRhoA causes the formation of head structures resembling the phenotype seen after coinjection of wnt inhibitors with dominant-negative BMP receptor. Since dominant-negative XRhoA is able to reduce the formation of head structures, we propose that XRhoA activity is essential for head formation. Thus, XRhoA may have a dual role in the embryo by regulating cell adhesion properties and pattern formation.

Amino Acid Sequence↗
PubMed1999

[Pulmonary function after allogeneic hematopoietic stem cell transplantation].

This study was undertaken to identify the factors influencing pulmonary function in patients who underwent hematopoietic stem cell transplantation (HCT). Pulmonary function tests were evaluated before and after HCT in 51 adult patients who underwent HCT between 1993 and 1998. The patients with hematologic malignancies were given total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Six patients suffered from acute GVHD above grade II and 27 patients suffered from chronic GVHD. The post-transplant % diffusing capacity (%DLco) 100 days after HCT was significantly lower than pretransplant values (82 +/- 21% versus 71 +/- 15%, p < 0.01). The %DLco at 100 days was significantly lower in patients with chronic GVHD than in patients without chronic GVHD (66 +/- 16% versus 77 +/- 9%, p < 0.05). These findings suggested chronic GVHD is related to the decreased %DLco values observed 100 days after HCT.

Adolescent↗
PubMed1998

Autoimmune hemolytic anemia.

Six types of autoimmune hemolytic anemias have been described. Table 1 provides summary highlights for each type of AIHA. WAIHA accounts for the majority of cases, followed by CAIHA and DIAHA. In recent years, AIHA status post-BMT has been noted to occur more often than previously reported, particularly in T-cell-depleted graft recipients. The clinical presentation is diverse among the various types of AIHAs: WAIHA cases may require a complex treatment regimen if unstable hemolytic anemia is present, and often permanent remission is infrequent. In contrast, CAIHA in younger patients (status postinfection) is frequently asymptomatic and self-limiting. If AIHA is suspected in a patient with clinically significant presentation, it is important to communicate with the transfusion service since specific tests to confirm these diagnoses are not routinely done. Special procedures may be necessary to identify underlying rbc alloantibodies prior to transfusion. In a patient pre-operative for cardiopulmonary-bypass surgery, CAIHA antibody testing should be done. When found, pre-operative management may lessen the risk of serious consequences such as hemolysis, renal failure, and myocardial damage. AIHA associated in BMT recipients is frequently severe, and, in some cases may be refractory to treatment despite complex management strategies. Further studies are needed to acquire a better understanding of the pathogenesis of BMT-associated AIHA.

Anemia, Hemolytic↗