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Biomedical subjects

A Watanabe

Publications and source records attributed to A Watanabe.

At least 523 records · Page 29Linked to original sources

[Crystal morphological and habit investigations of crystalline drugs. III. Sulfamethizole, levodopa and phenobarbital].

Crystal morphology and habit analyses necessary for a pharmaceutical technique have been studied by a polarizing microscope for tiny crystals of sulfamethizole, levodopa and phenobarbital listed in the Japanese Pharmacopoeia XII. Measurement of key refractive indices by an immersion method has been tried semiautomatically using photographs and the kit of immersion oils produced at 0.005 intervals, and a decision of an orientation of the section has been also carried by conoscope using photos. From the orthographic projections produced by the habit analysis of the colored photo as mentioned in the previous reports morphological and optical properties were clarified.

Crystallization↗

Electron microscopic studies on the inhibition of degranulation of rat mast cells by a novel anti-allergic agent, PTPC.

When rat mast cells sensitized by IgE antibody were exposed to antigen, transmission electron microscopy revealed alteration of the granules, cavity formation by fusion of the perigranular membrane and granule release by the fusion of the cavity membrane with the mast cell membrane. Scanning electron microscopy disclosed the extrusion of smooth and round bodies from pores formed on the cell surface. These changes were accompanied by the release of histamine. The inhibition of this degranulation by a novel anti-allergic agent, 6-(1-pyrrolidinyl)-N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamide (PTPC), was evaluated quantitatively as an inhibition of the granule alteration and cavity formation. At a concentration of 100 nM, PTPC inhibited the granule alteration and cavity formation as well as histamine release. In the same concentration, PTPC significantly increased the cyclic AMP content in the mast cells. These results suggest that the inhibition of the morphological changes in mast cells by PTPC might be due to the increased cyclic AMP caused by the agent and plays an important role in the suppression of chemical mediators release.

Animals↗

Progression of bone disease without deterioration of hematological parameters in a child with Gaucher disease during low-dose glucocerebrosidase therapy.

Gaucher disease is the most prevalent lysosomal storage disease. Although the efficacy of the macrophage-targeted human placental glucocerebrosidase is well known, it is still difficult to develop definitive guidelines regarding the appropriate therapy schedule. We describe an 8-year-old Japanese boy with Gaucher disease who had avascular necrosis of the right femoral head without deterioration of hematological variables during low-dose enzyme replacement therapy (12-13 IU/kg). This case demonstrates that continuous normal hematological findings may not preclude progression of other aspects of Gaucher disease in some patients during enzyme replacement therapy.

Blood Cell Count↗

Magnetic resonance imaging of ecchordosis physaliphora--case report.

A rare case of ecchordosis physaliphora clearly demonstrated by magnetic resonance (MR) imaging is described in a 48-year-old male who presented with right hearing disturbance and reduction in sensation in the right side of his face due to a large cystic schwannoma. MR imaging revealed the large cystic schwannoma as well as an abnormal clival lesion. The clival lesion was hypointense on T1-weighted images and hyperintense on T2-weighted images, and not enhanced by gadolinium-diethylenetriamine-penta-acetic acid (Gd-DTPA) administration. The clival lesion was partially removed. The histological diagnosis was ecchordosis physaliphora. The postoperative course was uneventful. The absence of enhancement of ecchordosis physaliphora by Gd-DTPA administration may be a characteristic finding, in contrast to chordoma which is generally enhanced.

Brain Neoplasms↗

Effects of rhG-CSF (filgrastim) on the recovery of hematopoiesis after high-dose chemotherapy and autologous peripheral blood stem cell transplantation in children: a report from the Children's Cancer and Leukemia Study Group of Japan.

In a nonrandomized study, hematopoietic recovery kinetics were evaluated in 98 consecutive patients who underwent high-dose chemotherapy without total body irradiation (TBI) and autologous peripheral blood stem cell transplantation (PBSCT). Fifty-three patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF) (filgrastim) therapy after PBSCT, and the data were compared by actuarial analysis to those of 45 historic controls. The number of days required to achieve a white blood cell count (WBC) of 1 x 10(9)/L, an absolute granulocyte count (AGC) of 5 x 10(8)/L, and a platelet count (PLT) of 5 x 10(10)/L were, respectively, 12.8 +/- 6.4 (mean +/- standard deviation [SD]), 13.4 +/- 6.4, and 49.2 +/- 78.2 in treated patients vs. 12.8 +/- 4.6, 14.4 +/- 10.3, and 31.4 +/- 38.8 days in historic controls, with no significant differences. There was no significant difference between the average number of days with fever in the treated group (6.0 +/- 6.6) and that in the control group (4.0 +/- 2.8). All febrile episodes responded promptly and successfully to parenteral antibiotic therapy. Thus, the data may suggest the possibility that therapy with filgrastim has only a limited ability to enhance hematopoietic recovery after PBSCT. To confirm this notion, we initiated a prospective randomized trial by recruiting a larger number of patients.

Adolescent↗

Suppression of the thyrotropin response to thyrotropin-releasing hormone and its association with severity of critical illness.

OBJECTIVE: To study whether the suppression of the thyrotropin (thyroid-stimulating hormone, TSH) response to thyrotropin-releasing hormone (TRH) correlates with severity of illness and death in patients with nonthyroidal critical illness. DESIGN: Prospective study. SETTING: Intensive care unit (ICU) of a university hospital. PATIENTS: Forty-one critically ill patients without thyroid disease with multiple organ failure who were admitted to the ICU. MEASUREMENTS AND MAIN RESULTS: The TSH response to TRH was tested within 24 hrs of ICU admission. Blood samples were obtained just before, and at 15, 30, 60, 90, and 120 mins after 500-micrograms injection of synthetic TRH. Triiodothyronine, free-triiodothyronine, thyroxine, free-thyroxine and TSH concentrations were measured in the samples obtained just before TRH injection. Acute Physiology and Chronic Health Evaluation (APACHE II) scores and Sepsis scores were calculated based on the data obtained within 24 hrs of ICU admission. Individual variables were compared between survivors and nonsurvivors. The APACHE II scores and Sepsis scores of nonsurvivors were significantly higher than those scores of survivors. The overall occurrence of suppressed TSH response to TRH was 88%. Peak TSH concentration of the TSH response was significantly lower in nonsurvivors than in survivors. Serial measurement of the TSH response showed that nonsurvivors experienced a decrease in peak TSH concentration from 1.55 +/- 0.78 to 0.55 +/- 0.30 microIU/mL; in survivors, it increased from 2.10 +/- 0.26 to 7.38 +/- 1.83 microIU/mL. Conversely, the basal TSH concentration did not change in either survivors or nonsurvivors. The "severity" of illness of nonsurvivors remained high; their mean APACHE II score varied from 20.0 +/- 1.9 to 22.1 +/- 1.3 and the mean Sepsis score varied from 20.0 +/- 4.3 to 25.4 +/- 4.0, while the same scores for survivors decreased significantly (p < .05): their APACHE II score decreased from 16.2 +/- 0.7 to 7.6 +/- 2.0 and the Sepsis score went from 14.0 +/- 1.9 to 6.0 +/- 1.6. CONCLUSIONS: In critically ill patients with multiple organ failure, suppression of the TSH response to TRH frequently occurs and correlates with severity of illness and outcome. Our data indicate that measurement of the TSH response is helpful in evaluating the severity of illness and prognosis for critically ill patients.

APACHE↗

[Clinical studies on biapenem (L-627) in the pediatric field].

Biapenem (L-627) was given intravenously to 17 children with acute bacterial infections including 3 with purulent tonsillitis, 1 with bronchitis, 4 with pneumonia, 2 with sepsis, 3 with pyelonephritis, 2 with SSSS. (2 cases are omitted from evaluation because of Mycoplasma pneumonia and infectious mononucleosis). Daily dosages per kg bodyweight ranging from 18.3 to 60 mg were given in 3 divided doses per day for 4 to 6 days. Clinical responses were excellent in 12 (80%), good in 2 (13.3%), fair in 1 (6.7%) and poor in 0 (0%), with an overall efficacy rate of 93.3%. Good bacteriological responses were obtained in all of the 9 cases from which pathogens were identified. A side effect is observed in only 1 case with mild diarrhea. The above results suggest that L-627 is a useful new carbapenem derivative for the treatment of bacterial infections in children.

Bacterial Infections↗

Assessment of testicular biopsy after cessation of maintenance chemotherapy in childhood acute lymphoblastic leukemia: a report from the Children's Cancer and Leukemia Study Group.

Among 484 male patients with acute lymphoblastic leukemia (ALL) registered into the protocols CCLSG 811, 841 and 874, from 1981 through 1990, 246 patients completed their protocols and were in continuous complete remission (CCR) for more than 3 years. One hundred and seven patients received bilateral testicular biopsies at the time of cessation of maintenance chemotherapy. Eight patients (7.5%) were found to have occult testicular leukemia (TL). Three of them did not receive any additional therapy and all suffered subsequent relapses; one bone marrow relapse and two testicular relapses. The other 3 patients received testicular radiation combined with an additional 2 years of chemotherapy, resulting in CCR for more than 6 years 10 months, 7 years 6 months, and 8 years 6 months. One with chemotherapy alone and another with radiation alone showed subsequent relapse. Overt TL after negative initial biopsy was developed in 3 (3.0%) of the 99 patients. All of them received testicular radiation with chemotherapy, resulting again in CCR for more than 1 year 0 months and 5 years 3 months; one patient showed relapse in testes and bone marrow after 3 years 8 months of CCR. These studies suggested that occult TL has an adverse prognostic significance unless retrieval chemotherapy is given and that performance of testicular biopsy at completion of maintenance chemotherapy is not contributory to prolongation of disease-free survival for males with ALL because the treatment employing testicular radiation plus retrieval chemotherapy for both occult TL and isolated overt TL after off-therapy is similarly very effective.

Antineoplastic Combined Chemotherapy Protocols↗

[Hodgkin's disease initially presenting as vertebral lesions and a solitary pulmonary nodule--a case report].

Hodgkin's disease rarely involves bones and lungs without causing marked lymph node enlargement. The case of a 36 year old man, who initially presented with vertebral lesions and a solitary nodule in the lung, is reported. At the initial presentation, no apparent lymph node enlargement was observed. Pathological examination of the specimens obtained at vertebral surgery and needle biopsy of the lung suggested a presumptive diagnosis of Histiocytosis X. However, a definite diagnosis of the Hodgkin's disease was made by biopsy of a cervical lymph node which newly enlarged about two years after his initial presentation. This case suggests variability in the clinical feature of Hodgkin's disease.

Adult↗

[A case of Wegener's granulomatosis with episcleritis, mediastinal lesions, and pleural effusion and without serum anti-neutrophil cytoplasmic antibodies].

We report a 63-year-old male case of Wegener's granulomatosis. His complaints were cough and fever, and chest X-ray showed subpleural infiltrative opacities in the bilateral lungs and small nodular lesions in the middle portion of the right lung. He had been treated as bacterial pneumonia at another hospital without any improvement and was referred to this hospital. Chest CT scan disclosed several small nodular lesions in the subpleural region of the right lung, consolidation in the posterior mediastinum, and the left pleural effusion. Transbronchial lung biopsy revealed inflammatory granulation with predominantly lymphocytes and micro-necrosis in the peribronchiolar region. Although these findings suggested Wegener's granulomatosis, open lung biopsy was performed because both antineutrophil cytoplasmic antibodies (ANCA) and antibodies to proteinase-3 were negative and ear, nose, and throat abnormalities were not found. Pathologic findings consisted mainly of granulomatous inflammation with lymphocytes, histiocytes, and multinucleated giant cells, and granulomatous vasculitis with micro-necrosis. Furthermore, the patient was diagnosed as having bilateral episcleritis by an ophthalmologist. No renal involvement was found. Standard treatment with cyclophosphamide and glucocorticoid resulted in marked improvement within a couple of weeks, and the patient was in complete remission eight months after initiation of therapy. This case is of interest in that the distribution of lesions was not typical and ANCA was negative.

Antibodies, Antineutrophil Cytoplasmic↗

[Symbas's operation in a case of congenital fistula of the right coronary artery to left ventricle].

Congenital fistula between a coronary artery and the left cardiac ventricle are extremely rare. Since Blakeway (1918) first described this type of anomaly, only 72 cases have been reported up to the present, within our knowledge. A surgical correction of congenital fistula of the right coronary artery to left ventricle in a 36 year-old woman who suffered from easy fatigability is reported. This lesion was deduced after echocardiography identified a dilated right coronary artery and fluttering of the posterior cusp of the mitral valve throughout the diastole, the diagnosis was confirmed by retrograde aortography and coronary angiography. The fistula was closed by Symbas's operation under cardiopulmonary bypass with cardiac arrest and mild hypothermia. Postoperative recovery was uneventful. Coronary angiography one month after the operation revealed that the right coronary artery was still dilated with thrombus; there were no signs of myocardial ischemia or infarction. This diagnosis and successful treatment were based on careful study of the documentation of the 72 previously reported cases.

Adult↗

[Effects of ulinastatin on extravascular lung water volume in patients undergoing cardiopulmonary bypass].

Pulmonary dysfunction often follows cardiopulmonary bypass (CPB). In the present study, we examined (1) the effects of the human urinary tripsin inhibitor ulinastatin on the extravascular lung water volume (EVLW), and (2) A-aDO2 as an indicator of pulmonary function, in 30 adult patients undergoing CPB. We administered 600,000 U of ulinastatin intravenously immediately before start of CPB in 15 patients (U group). In the control group without ulinastatin, remarkable transient increases in EVLW and A-aDO2 occurred after CPB. In contrast, in the U group extravascular lung water volume level was maintained within the normal range and an inhibited transient increase in A-aDO2 after CPB was observed. We conclude that the administration of ulinastatin in patients undergoing CPB may be useful to prevent pulmonary dysfunction following CPB.

Cardiopulmonary Bypass↗

Modulation of [3H]mazindol binding sites in rat striatum by dopaminergic agents.

This study was undertaken to examine whether repeated alteration of dopamine turnover influences the function of dopamine uptake sites. In the first experiment, rats were repeatedly injected intraperitoneally with L-3,4-dihydroxyphenylalanine (L-DOPA), alpha-methyl-p-tyrosine or 1-[2-bis(4-fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl)piperazine (GBR 12909) once daily for 14 days. An increase in the number of [3H]mazindol binding sites in the striatum was seen with L-DOPA and GBR 12909. A decrease was seen with alpha-methyl-p-tyrosine. In the second experiment, the effect of a single treatment with the same drugs was investigated and no change in the number and affinity of [3H]mazindol binding sites was found. These results indicate that the number of dopamine uptake sites is modulated by persistent changes in dopamine turnover, and that repeated treatment with a selective dopamine uptake inhibitor, GBR 12909, increases their number.

3,4-Dihydroxyphenylacetic Acid↗

In vivo phosphorylation sites in fetal and adult rat tau.

Fetal tau and tau in paired helical filaments show similar immunoreactivities with several phosphorylation-dependent paired helical filament-polyclonals and monoclonals, suggesting that the two molecules share several distinct phosphorylated epitopes. To make clear the similarities and differences between the two, we have undertaken work to identify the in vivo phosphorylation sites in fetal rat tau. We have approached this problem by identifying phosphopeptides by means of mass spectrometry and sequencing of those phosphopeptides after modification with ethanethiol. Although remarkable heterogeneity was present, fetal tau was found to bear at most 10 phosphates at Ser-189, Ser-190, Ser-193, Ser-226, Ser-387, Ser-395, Thr-172, Thr-222, and, presumably, Ser-391 and Thr-208 (numbering is according to the longest form of rat tau; Kosik, K. S., Orecchio, L. D., Bakalis, S., and Neve, R. L. (1989) Neuron 2, 1389-1397). In contrast, adult rat tau was much less phosphorylated; only Thr-172, Ser-190, Ser-193, Thr-222, and Ser-395 were phosphorylated to a slight-to-moderate extent. All these sites except for Ser-189 and Ser-391 were followed by Pro residues. Thus, tau is an in vivo substrate for proline-directed protein kinase(s), and its phosphorylation state is developmentally regulated.

Aging↗

Formation of distal structures from stumps of chick wing buds at stages 24-25 following the grafting of quail tissue from X-irradiated distal limb buds.

To examine the regulatory activity of the proximal region of chick limb buds, distal halves of chick wing buds at stages 24-25 were removed, and the distal tips of X-irradiated stage 21 quail limb buds with an apical ectodermal ridge (AER) were grafted onto the chick stumps. The host stumps formed only humerus after removal of the donor distal tips or with tip mesoderm alone. However, when distal tips with an AER were grafted onto the stumps, one or two cartilage elements of host origin were formed at the distal end of the humerus. To examine whether the stump cells have changed to cells of a more distal, progress zone (PZ) cells, the chick stumps with quail tips were immunostained with antibody against AV-1, which reacts with the anterior PZ region of chick limb buds and is specific for an antigen that is expressed under the control of the AER. Within two days of grafting, cells positive for the antigen reappeared in the stump tissues. These results suggest that the some of the stump cells may be converted to PZ cells and their positional values may change to those of more distal structures under the influence of the AER.

Animals↗