Biomedical subjects

T Shirai

Publications and source records attributed to T Shirai.

At least 109 records · Page 6Linked to original sources

PubMed2000

Effects of hemoglobin on pulmonary arterial pressure and pulmonary vascular resistance in patients with chronic emphysema.

BACKGROUND: The increase in viscosity caused by secondary polycythemia is thought to be one of the major causes of pulmonary hypertension secondary to chronic emphysema. However, very few clinical studies considered the relation between pulmonary hypertension and polycythemia in the case of chronic obstructive pulmonary disease. OBJECTIVE: The purpose of this study is to elucidate the relative contribution of an increase in hemoglobin level (Hb) to mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR). METHODS: We retrospectively investigated 41 patients with chronic emphysema who had undergone a right heart catheterization. Multiple-regression analysis and F test were performed to investigate both direct effects of Hb and PaO(2) as independent variables on mPAP and PVR as dependent variables. RESULTS: Significant correlations were found between PaO(2) and mPAP (or PVR), or Hb and mPAP (or PVR), indicating that both Hb and PaO(2) are contributory to mPAP and PVR. The F test demonstrated that Hb and PaO(2) could directly affect the level of either mPAP or PVR. CONCLUSIONS: It was concluded that Hb had a direct effect on mPAP and PVR, independently of hypoxia in patients with chronic emphysema.

Aged↗

PubMed2000

Seven-color fluorescence imaging of tissue samples based on Fourier spectroscopy and singular value decomposition.

Seven-color analyses of immunofluorescence-stained tissue samples were accomplished using Fourier spectroscopy-based hyperspectral imaging and singular value decomposition. This system consists of a combination of seven fluorescent dyes, three filtersets, an epifluorescence microscope, a spectral imaging system, a computer for data acquisition, and data analysis software. The spectra of all pixels in a multicolor image were taken simultaneously using a Sagnac type interferometer. The spectra were deconvolved to estimate the contribution of each component dye, and individual dye images were constructed based on the intensities of assigned signals. To obtain mixed spectra, three filter sets, i.e., Bl, Gr, and Rd for Alexa488 and Alexa532, for Alexa546, Alexa568, and Alexa594, and for Cy5 and Cy5.5, respectively, were used for simultaneous excitation of two or three dyes. These fluorophores have considerable spectral overlap which precludes their separation by conventional analysis. We resolved their relative contributions to the fluorescent signal by a method involving linear unmixing based on singular value decomposition of the matrices consisting of dye spectra. Analyses of mouse thymic tissues stained with seven different fluorescent dyes provided clear independent images, and any combination of two or three individual dye images could be used for constructing multicolor images.

Animals↗

PubMed2000

Autoantibody responses to cardiolipin and DNA in infancy: association with lymphocytic panniculitis.

We report an infant with anticardiolipin (aCL) antibodies who presented with erythematous nodular skin lesions and elevated liver enzyme levels. The cutaneous manifestation was histologically lymphocytic lobular panniculitis with vasculitic and hemorrhagic changes. The infant also had low levels of anti-double stranded DNA (dsDNA) and anti-single stranded DNA (ssDNA) antibodies. There were no detectable antibodies to small nuclear ribonucleoproteins including Ro/SSA and La/SSB. His mother was consistently seronegative for any of these antibodies. Without corticosteroid therapy, cutaneous lesions resolved and anticardiolipin antibodies, but not anti-dsDNA and ssDNA antibodies, normalized within 16 months after the onset of the disease. Our patient demonstrated an uncommon presentation of aCL related cutaneous manifestation, the presentation with panniculitis being only the third such patient reported in the literature. Of great interest was the appearance of aCL antibodies and skin lesions during very early infancy.

Adult↗

PubMed2000

Modifying effects of propolis on MeIQx promotion of rat hepatocarcinogenesis and in a female rat two-stage carcinogenesis model after multiple carcinogen initiation.

The modifying effects of the dietary administration of water- and ethanol-extracted propolis produced in Brazil (WB and EB, respectively) on 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) promotion of rat hepatocarcinogenesis were investigated in a medium-term liver bioassay system with use of male Fischer 344 rats. The number and area of glutathione S-transferase placental form (GST-P)-positive foci in rats given 0.5% WB were significantly increased compared with the group given MeIQx alone. Furthermore, the numbers of GST-P-positive foci were higher in rats given 0.1% WB or EB than in those given the basal diet alone. The modifying effects of propolis on other organs were also examined in female Fischer 344 rats given multiple carcinogens for initiation. Rats received water- and ethanol-extracted propolis produced in Brazil and Uruguay (WB, EB, WU, and EU, respectively) in the diet after exposure to three different carcinogens. The incidence of total mammary tumors was significantly lower in rats given EU than in the control group. These results indicate that a water extract of propolis exerts a cocarcinogenic effect on MeIQx hepatocarcinogenesis while promoting the effect at low dose in a two-stage hepatocarcinogenesis model. Moreover, they suggest that ethanol-extracted propolis may be an inhibitor of mammary gland carcinogenesis.

Alkylating Agents↗

PubMed2000

The involvement of two specific arginine residues in the action of HM-1 killer toxin was deduced from site-directed mutagenesis.

Each of the four arginine residues in the HM-1 killer toxin was replaced by alanine using site-directed mutagenesis. The polymerase chain reaction (PCR)-constructed mutant gene was successfully expressed in HM-1 toxin resistant Saccharomyces cerevisiae. Among four HM-1 toxin analogues, R82A HM-1 toxin and R86A HM-1 toxin lost killer activity, while R61A HM-1 toxin and R85A HM-1 toxin retained activity. These results strongly indicate the importance of the arginine residues at positions 82 and 86 which are located in the C-terminal region of the HM-1 toxin for the action of killer activity.

Arginine↗

PubMed2000

Atypical Fabry's disease presenting with cholesterol crystal embolization.

We describe a 65-year-old man who presented with pulmonary hemorrhage and progressive renal insufficiency three months after resection surgery for an abdominal aortic aneurysm. Intensive treatment with corticosteroids and hemodialysis were not effective, and the patient died. Postmortem examination of the kidneys revealed widespread cholesterol clefts within the renal arterioles and a number of lamellar inclusion bodies were observed by electron microscopy. The diagnosis of Fabry's disease was made by the absence of plasma alpha-galactosidase A activity. This was a very rare case of subclinical Fabry's disease coexistent with cholesterol crystal embolization, mimicking pulmonary-renal syndrome.

Aged↗

PubMed2000

Preface and overview: genetics of SLE; a sine qua non for identification.

Clinical manifestations of systemic lupus erythematosus (SLE) are extremely diverse and variable, mainly because SLE is a multi-factorial disease. Variable combinations of contributing genes at multiple loci in individual patients probably result in diverse disease phenotypes. Genes that predispose to SLE are undoubtedly related to key events in pathogenesis, and may involve a variety of genes in immune system. These genes are currently unidentified, mostly because of the complexity of multi-factorial inheritance. Recently, the application of the polymerase chain reaction and the availability of maps of microsatellites have facilitated a genome-wide scan to define the number and locations of genes for complex traits. However, extensive genetic heterogeneities and polymorphisms and complex modes of inheritance of disease phenotypes have delayed completion of a genome-wide analysis of susceptibility loci for human SLE. Since many SLE-susceptibility genes show low penetrance, several hundred affected sibpairs are assumed to be necessary to show linkages for many of the contributing loci. In this respect, studies of polymorphisms and functions of candidate genes suggested based on studies on murine models may contribute to studies on SLE patients and their relatives. Major genetic loci have been mostly identified in SLE-prone mouse strains. Nevertheless, identity of natures, functions and roles in the pathogenesis of SLE remains undetermined. Considering the possibility of clustering of susceptibility loci in a particular chromosomal interval, the final goal for identification of susceptibility genes will largely depend on the generation of mutant SLE-prone mice with homologous recombination of the potential target gene. Extensive reviews collected here are expected to form the basis for identification of target genes and for clarification of the genetic mechanisms underlying SLE.

Animals↗

PubMed2000

Genetic aspects of inherent B-cell abnormalities associated with SLE and B-cell malignancy: lessons from New Zealand mouse models.

Genes that predispose to SLE are closely related to key events in pathogenesis of this disease. As much of the pathology can be attributed to high affinity autoantibodies and/or their immune complexes, some of the genes may exert effects in the process of emergence, escape from tolerance mechanisms, activation, clonal expansion, differentiation, class switching and affinity maturation of self-reactive B cells. A number of growth and differentiation factors and signaling molecules, including positive and negative regulators, are involved in this process. Genetic variations associated with functional deficits in some of such molecules can be involved in the susceptibility for SLE. As is the case with SLE, hereditary factors play significant roles in the pathogenesis of B cell chronic lymphocytic leukemia (B-CLL). Patients with B-CLL or their family members frequently have immunological abnormalities, including those associated with SLE. It is suggested that certain genetically determined regulatory abnormalities of B cells may be a crossroad between B-CLL and SLE. A thorough understanding of the genetic pathways in B cell abnormalities leading to either SLE or B-CLL is expected to shed light on their association. New Zealand mouse strains are pertinent laboratory models for these studies. Chromosomal locations of several major genetic loci for abnormal proliferation, differentiation and maturation of B cells and relevant candidate genes, located in close proximity to these intervals and potentially related to the SLE pathogenesis, have been identified in these mice. Further studies make for a wider knowledge and understanding of the pathogenesis of SLE and related B-cell malignancy.

Animals↗

PubMed2000

[A 77-year-old man with gait and gaze disturbance].

We report a 77-year-old Japanese man with progressive gait disturbance. He was well until his 71 years of the age (1992), when he noted an onset of disturbance in his speech, which was followed by difficulty in using his left hand. He did not attempt to use his left hand afterwards. He started to fall down in the spring of 1994. He was admitted to our service on October 6, 1994. Neurologic examination revealed an alert and oriented man. He showed limb-kinetic apraxia in his left hand with anosognosia for his apraxia. Vertical gaze was impaired. He walked in small steps. He had moderate axial and limb rigidity. He had no weakness, ataxia, or tremor. Deep tendon reflexes were normal. Plantar response was flexor. Sensation was intact. His gait had progressively become worse and he was admitted to another hospital in April of 1996. At that time he was disoriented to time. He was only able to walk a few steps with support. He continued to show limb-kinetic apraxia in his left hand. He developed dementia and dysphagia and he expired on October 27, 1998. He was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had corticobasal degeneration. Most of the participants agreed with this diagnosis, but a few of them thought that progressive supranuclear palsy would be more likely. Post-mortem examination revealed no gross cortical atrophy. The right hemisphere was kept frozen for future biochemical analysis. The left precentral gyrus showed spongy changes, neuronal loss and gliosis. The pallidum, putamen, and the subthalamic nucleus were unremarkable, however, neurofibrillary tangles were seen in the subthalamic nucleus. The substantia nigra showed only slight neuronal loss; neuronal pigments were well retained. A few neurofibrillary tangles were seen in the remaining neurons. The cerebellar dentate nucleus showed grumose degeneration. Gallyas-Braak staining revealed many tuft-shaped astrocytes in the precentral gyrus. Pathologic diagnosis was progressive supranuclear palsy. Some participants thought that this diagnosis was unacceptable, because the pathologic changes in the substantia nigra, globus pallidus, and the subthalamic nucleus, which were usually severely involved in PSP, did not show typical changes of PSP. In addition, the predominant clinical feature was limb-kinetic apraxia, although he showed vertical gaze paresis and parkinsonian gait, which could also be seen in corticobasal degeneration. There was a big discussion among participants with regard to the diagnosis.

Aged↗

PubMed2000

[Mild intermittent aspirin-induced asthma in a patient who became asymptomatic after removal of pet hamsters from home].

A 25-year-old woman was admitted to our hospital because of wheeze, dyspnea, nasal obstruction, epiphora, and ear fullness. These symptoms occurred 30 minutes after the intake of 200 mg of ibuprofen and 100 mg of norfloxacin, which had been prescribed by a local clinic for an upper respiratory tract infection. The patient had kept 20 hamsters indoors and a dog outside for 1 year and a half. During the 9 months prior to admission, she had experienced nocturnal asthmatic symptoms, which were controlled by oral theophylline on an as-needed basis. She had seasonal rhinitis, but no sinusitis or nasal polyps. Serum total IgE was 98 U/ml, and tests for specific IgE antibodies to hamster epithelium and dog epithelium were both positive (class 2). The provocative concentration of methacholine causing a 20% fall in FEV1 was 4.7 mg/ml. After removal of the hamsters from her home, the patient became asymptomatic without further medication, and her airway hyper-responsiveness was also alleviated. Although inhalation challenge with 5% tolmetin failed to induce a positive reaction, the diagnosis of aspirin-induced asthma was confirmed by single-blind oral challenge with 100 mg of ibuprofen. The patient exhibited mild airway responsiveness as well as mild sensitivity to nonsteroidal anti-inflammatory drugs, differing from the severe and intractable clinical features of typical aspirin-induced asthma.

Adult↗

PubMed2000

[A 67-year-old man with progressive disturbance of gait].

We report a 67-year-old man with progressive disturbance of gait. He was well until the spring of 1993 (62 years of the age), when he noted an onset of unsteady gait. He also noted that he started to have a difficulty in playing tennis, in which he became unable to hit the ball with his racket. He also noted parkinsonian features such as bradykinesia and loss of hand dexterity. He was treated with levodopa, which did not improve his symptoms. His MRI revealed marked atrophy of the cerebellum and the pons. The criss-cross high signal lesion was seen in the center of the pons. The third ventricle was dilated. The putamen was unremarkable. His subsequent course was complicated by easy to fall, difficulty in swallowing with episodes of aspiration pneumonia. He also developed nocturnal apneustic episodes. He was admitted to our hospital on November 15, 1998, when he was 67 years of the age. He had low grade fever and low blood pressure (98/70). He was anemic but not icteric. Tumors were palpated in his jaw, anterior chest, and in the left arm. He was alert but unable to convey his desire because of dyspnea and tracheostomy. His gaze was slightly restricted in the horizontal direction and markedly so in the vertical direction. Motor functions were difficult to evaluate. His clinical course was complicated by atelectasis of the right lung and pleural effusion. He developed marked edema and oliguria. He developed sudden bradycardia and expired on December 26, 1998. He was discussed in a neurological CPC and the chief discussant arrived at the conclusion that the patient had multiple system atrophy. Majority of the audience agreed with this diagnosis. Post-mortem examination revealed a lung cancer in the right lung (undifferentiated adenocarcinoma) with metastases to the liver, kidneys, lymph nodes, pericardium, pleura, skin, bone marrow, and the brain. Neuropathologic examination revealed marked atrophy of the pons and the cerebellum. The putamen showed brownish discoloration and atrophic changes. The substantia nigra showed marked neuronal loss and gliosis. Oligodendrocytic inclusion bodies (alpha-synuclein positive) were seen in the putamen, globus pallidus, substantia nigra, pontine nucleus, cerebellar white matter, internal capsule, cerebral peduncle, and the spinal cord. These findings are consistent with the pathologic diagnosis of multiple system atrophy. What was interesting to us was the presence of neurofibrillary tangles in the substantia nigra, nucleus ruber, globus pallidus, and subthalamic nucleus. Tuft-shaped astrocytes were also seen. This patient appears to be a rare example of combination of MSA and PSP.

Adenocarcinoma↗

PubMed2000

[A comparative study of the prognosis for Japanese patients with idiopathic interstitial pneumonia or BOOP based on histopathologic subsets].

We explored the prognosis for 123 patients with either idiopathic interstitial pneumonia (IIP) or bronchiolitis obliterans organizing pneumonia (BOOP). All patients underwent either open lung biopsy or thoracoscopic lung biopsy procedures. The histopathologic diagnosis of IIP included patients with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and desquamative interstitial pneumonia with respiratory bronchiolitis-associated interstitial lung disease. The prognosis was poorest for patients with a histologic diagnosis of UIP, and excellent for those who received a diagnosis of BOOP. Although the prognosis is generally considered to be good for patients with NSIP, some NSIP patients in our study died. Histopathologic diagnosis based on surgical lung biopsy is useful in evaluating the prognosis for patients with IIP.

Aged↗

PubMed2000

[A patient with recurrent uterine cervical cancer successfully treated by combined modality therapy including local injection of anticancer agents based on CDDP].

The patient was a 77-year-old woman who had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy following the diagnosis of uterine cervical cancer at the age of 57. A recurrent tumor was detected on the anterior surface of the right iliopsoas muscle and fine needle aspiration of the tumor revealed squamous cell carcinoma. A needle was inserted into the tumor under transabdominal ultrasound guidance, and anticancer agents, chiefly cis-diamminedichloroplatinum [II] (CDDP), were injected. The patient also received systemic chemotherapy (CAP therapy) and radiotherapy. Subsequently, computed tomography showed a 73% reduction in the size of the tumor. A mass 7 cm in diameter was still present on the anterior surface of the iliopsoas after treatment, but tumor markers fell to normal levels. The patient is presently receiving UFT (600 mg/day) as maintenance therapy. At 48 months after recurrence, there has been no increase in the tumor size or tumor marker levels, and the performance status is grade 0. In conclusion, a good outcome was achieved by local injection of anticancer agents combined with systemic chemotherapy and radiotherapy, and there were few side effects.

Aged↗

PubMed2000

[Endocrine disrupting chemicals and carcinogenesis--breast, testis and prostate cancer].

Since exogenous hormones, including hormonal medicines such as diethylstilbestrol (DES), have been shown carcinogenic potentials in human and animals, it has been worried about whether endocrine disrupting chemicals(EDCs) have also carcinogenic potentials at their target organs, such as prostate, mammary gland, testes, uterus, ovary, thyroid, etc. In experimental animals, mammary tumors are induced by some pesticides, such as DDT and atrazine. Although testicular tumors are also induced by some EDCs, such as DES and E2, most of tumors are interstitial cell tumors, but not germ cell tumors, which are most common testicular tumors in man. Epidemiological studies showed that there is no EDC which clearly possess carcinogenic potentials in man, except dioxin and hormonal medicines.

Animals↗

PubMed1999

Post-initiation effects of a super critical extract of propolis in a rat two-stage carcinogenesis model in female F344 rats.

Post-initiation modifying effects of dietary administration of a super critical extract of propolis on major organs were examined using a two-stage carcinogenesis model. Groups of 21 or 22 F344 female rats were treated sequentially with 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN, i.g.), 7,12-dimethylbenz[a]anthracene (DMBA, i.g.), 1,2-dimethylhydrazine (DMH, s.c.) and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN, in drinking water) during the first 3 weeks for initiation, and then administered diet containing 0.1 or 0.01% propolis for 33 weeks. Further groups were treated with the carcinogens alone, 0.1% propolis alone or basal diet alone. All surviving animals were killed at week 36, and major organs were examined histopathologically for development of preneoplastic and neoplastic lesions. The incidence and multiplicity of mammary carcinomas were significantly decreased by the 0.1 and 0.01% propolis treatments. In the urinary bladder, the incidence of PN hyperplasia but not tumors was, in contrast, significantly increased by 0.1% propolis. Similarly, the number and area of glutathione S-transferase placental form (GST-P)-positive liver foci were significantly elevated with this high dose. The results indicate that a low dose of a super critical extract of propolis may find application as a potent chemopreventor of mammary carcinogenesis.

1,2-Dimethylhydrazine↗

PubMed1999

Observation of Multi-TeV Gamma Rays from the Crab Nebula using the Tibet Air Shower Array.

The Tibet experiment, operating at Yangbajing (4300 m above sea level), is the lowest energy air shower array, and the new high-density array constructed in 1996 is sensitive to gamma-ray air showers at energies as low as 3 TeV. With this new array, the Crab Nebula was observed in multi-TeV gamma-rays and a signal was detected at the 5.5 sigma level. We also obtained the energy spectrum of gamma-rays in the energy region above 3 TeV which partially overlaps those observed with imaging atmospheric Cerenkov telescopes. The Crab spectrum observed in this energy region can be represented by the power-law fit dJ&parl0;E&parr0;&solm0;dE=&parl0;4.61+/-0.90&parr0;x10-12&parl0;E&solm0;3 TeV&parr0;-2.62+/-0.17 cm-2 s-1 TeV-1. This is the first observation of gamma-ray signals from point sources with a conventional air shower array using scintillation detectors.

Journal Article↗

PubMed1999

High-resolution structure of the conger eel galectin, congerin I, in lactose-liganded and ligand-free forms: emergence of a new structure class by accelerated evolution.

BACKGROUND: Congerin I is a member of the galectin (animal beta-galactoside-binding lectin) family and is found in the skin mucus of conger eel. The galectin family proteins perform a variety of biological activities. Because of its histological localization and activity against marine bacteria and starfish embryos, congerin I is thought to take part in the eels' biological defense system against parasites. RESULTS: The crystal structure of congerin I has been determined in both lactose-liganded and ligand-free forms to 1. 5 A and 1.6 A resolution, respectively. The protein is a homodimer of 15 kDa subunits. Congerin I has a beta-sheet topology that is markedly different from those of known relatives. One of the beta-strands is exchanged between two identical subunits. This strand swap might increase the dimer stability. Of the known galectin complexes, congerin I forms the most extensive interaction with lactose molecules. Most of these interactions are substituted by similar interactions with water molecules, including a pi-electron hydrogen bond, in the ligand-free form. This observation indicates an increased affinity of congerin I for the ligand. CONCLUSIONS: The genes for congerin I and an isoform, congerin II, are known to have evolved under positive selection pressure. The strand swap and the modification in the carbohydrate-binding site might enhance the cross-linking activity, and should be the most apparent consequence of positive selection. The protein has been adapted to functioning in skin mucus that is in direct contact with surrounding environments by an enhancement in cross-linking activity. The structure of congerin I demonstrates the emergence of a new structure class by accelerated evolution under selection pressure.

Amino Acid Sequence↗

PubMed1999

Chemoprevention of heterocyclic amine-induced carcinogenesis by phenolic compounds in rats.

Chemopreventive effects of synthetic and naturally occurring antioxidants on heterocyclic amine (HCA)-induced rat carcinogenesis and mechanisms of inhibition were assessed. In a medium-term liver bioassay, combined treatment with 0.03% 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and synthetic antioxidants such as 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), BHA, BHT, tert-butylhydroquinone (TBHQ) and propyl gallate, each at a dose of 0.25%, and troglitazone at doses 0.5 and 0.1%, potently inhibited development of glutathione S-transferase placental form (GST-P) positive foci as compared with MeIQx alone values. Of these antioxidants, HTHQ showed the greatest activity. Green tea catechins tended to inhibit GST-P positive foci development, while quercetin, rutin, curcumin, daidzin, ferulic acid and genistin all exerted significant enhancing effects. HTHQ also inhibited 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colon carcinogenesis in a two stage colon carcinogenesis model using 1,2-dimethylhydrazine (DMH) as an initiator. Immunohistochemically detected PhIP-DNA adduct positive nuclei in the colon induced by continuous oral treatment with 0.02% PhIP for 2 weeks decreased by the combined treatment with 0.5 or 0.125% HTHQ. Methoxyresorfin O-demethylase activity in rat liver microsomes in vitro was clearly inhibited by the addition of HTHQ, BHA, BHT, TBHQ or propyl gallate, with particularly strong inhibition being observed in HTHQ. However, the CYP1A2 level in rat liver increased after oral treatment with HTHQ for 2 weeks. These results indicate that synthetic antioxidants, HTHQ in particular, is a very strong chemopreventor of HCA-induced carcinogenesis. It is suggested that depression of metabolic activation rather than antioxidant activity is responsible for the observed effect. However, other mechanisms, including the effects on phase II enzymes cannot be ruled out.

Animals↗