[A new glucose 6-phosphate dehydrogenase (G6PD) variant (G6PD Niigata) with chronic hemolysis and liver hemochromatosis].
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Biomedical subjects
Publications and source records attributed to A Shibata.
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Two families who had been reported as having May-Hegglin anomaly were diagnosed as having Fechtner syndrome based on complication of renal disease, deafness and characteristic leukocyte inclusions. By Wright-Giemsa staining, the inclusions of neutrophils were smaller and stained less clearly than those seen in May-Hegglin anomaly. Ultrastructurally, the inclusions consisted of organelle-poor cytoplasm, containing small particles, which were probably ribosomes. Some inclusions contained only a few filaments or small remnants of rough endoplasmic reticulum (RER). The latter resembled the findings observed in Fechtner syndrome. They lacked the parallel arrays of filaments characteristic of May-Hegglin anomaly and the parallel strands of RER seen in toxic Döhle bodies. Renal disorders ranged from microscopic hematuria to renal failure requiring dialysis in one family and persistent proteinuria in the other family. Deafness was sensorineural type or combined type due to otitis media. Except for the fact that they lacked congenital cataracta, the findings in these two families were consistent with those in Fechtner syndrome.
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As compared with advances in the treatment of acute leukemia, we have made little progress in chronic leukemia. Recently we have attempted some new treatments for chronic phase of CML, and confirmed those effectiveness. But for blastic crisis, we still grope in the dark. In this paper, we review the chemotherapy of CML and CLL including new treatments except bone marrow transplantation.
Tissue blocks and vascular casts of the human spleen were studied by scanning electron microscopy. Splenic pulp was composed of white pulp packed with lymphocytes and red pulp which consisted of three dimensional reticular meshwork and splenic sinus. There were at least three types of microcirculation with different functions in the human spleen. First, open circulation in the red pulp is engaged in highly sensitive clearance of foreign materials in blood by numerous macrophages resided in splenic cord (culling function). It is also engaged in pitting function by narrow slits of the sinus. The second is the closed circulation occurred in the red pulp in the human spleen. It was represented as an arteriolar labyrinth whose endothelial cells connected with those of sinuses. Blood flow through this circulation is exposed to small number of macrophages in the sinus. It probably corresponds to the fast blood flow in the spleen. Third, microcirculation to the white pulp and marginal zone is engaged in phagocytosis of foreign materials in blood and carriage of their antigenic portions to lymphocytes in the white pulp. Therefore variation of the blood flow through their circulation may bring about a change of the splenic function. Relationship among blood flow, nerve stimulation and immune reaction was discussed.
In Japan, pulmonary thromboembolism (PTE) is rare and the therapy of this disease, especially the thrombolytic therapy, has not been established yet. We studied the effect of thrombolytic therapy by urokinase (UK) in eighteen patients with PTE. We also compared the results with those in Europe and the United States. Eighteen patients (male 7, female 11) were 27 yo to 77 yo (mean 55 yo). Seven cases were mild and 11 cases were moderate to severe. The initial dosage of UK administration was 2.4 x 10(5) to 7.2 x 10(5) IU with the mean of 4.1 x 10(5) IU, which was approximately the double of those in Europe and the US. The duration of UK therapy was 1 to 9 days with the mean of 4.8 days. It was longer than in Europe and the US (12-24 hours). Total amount of UK in each case ranged 4.8 x 10(5) to 42 x 10(5) IU (mean 19.3 x 10(5) IU) with the daily dosage of 4.0 x 10(5) IU in average. They were almost half of those in Europe and the US. Clinical signs and laboratory findings subsided in 1-7 day by UK administration in 14 cases (87%) with the reduction of defects on perfusion lung scans and all of these cases survived. No severe complications were found in any cases. We conclude that the thrombolytic therapy with UK in Japan might be acceptable from the results of this present study. However, the prospective study of thrombolytic therapy on a larger scale remains to be done in the future.
Echocardiographic features of 221 alcoholics after total abstinence were investigated. At the time of admission, none demonstrated left ventricular (LV) enlargement. Noticeably, 26% patients out of the total showed LV wall thickening more than 1.4 cm in the interventricular septum. On the other hand, 19% of the alcoholics illustrated hypokinetic LV wall without chamber dilatation which was either less than 55% in ejection fraction or 30% in fractional shortening. Three months later, the LV wall thickness reduced significantly from 1.6 to 1.4 cm in average and the LV wall motion improved significantly from 27 to 31% in fractional shortening. In the cases with wall thickening, the change was well correlated with a decrease both in heart rate and in LV muscle volume, but not with a decrease in systemic blood pressure. No significant correlated factors could be detected in the hypokinetic cases.
A 27-year-old woman had a history of palpitation at the age of nine. Ventricular tachycardia (VT) was detected four years ago and treatment with procainamide was started. Physical examination disclosed nothing abnormal other than an apical mid-systolic click. Electrocardiogram and chest radiograph were normal, and echocardiogram disclosed borderline mitral valve prolapse (MVP). VT was not provoked by exercise, and Holter monitorings of electrocardiogram were always within a normal limit. Angiography was normal. Electrophysiological study disclosed VT by left ventricular stimulation and the earliest activation was at the apex, VT was abolished by early stimulation from the right ventricular apex. The association of a mid-systolic click and VT was interesting in this case. When the patient had a systolic click at the outpatient clinic, VT frequently occurred within a month (six of seven times), while VT did not occur without an audible systolic click (three of four times). Although it is uncertain whether VT of this patient has any relationship to MVP or to the click, these problems remain to be solved in the future.
A 67-year-old man was admitted in October 1987 with complaints of nausea, headache, dizziness and speech disturbance. Hematological examination showed pancytopenia. Bone marrow aspiration failed with a dry tap. A month later, the second aspiration showed hypocellular marrow containing 18.2% of lymphoma cells. Physical examination showed splenomegaly and lymph node swelling. Polyclonal hypergammaglobulinemia was not observed. A lymph node biopsy exhibited typical histology of immunoblastic lymphadenopathy (IBL)-like T cell lymphoma. Surface marker CD3 and CD4 positive cells were dominant. The patient complained of epigastric pain and occult blood was positive in stool. Gastrofiberscopic examination disclosed well differentiated adenocarcinoma in situ located on a polyp, and polypectomy was performed. Lymphoma was treated with cyclophosphamide, doxorubicin, vinblastine and prednisolone. Splenomegaly and lymph node swelling were reduced in size but the effect was temporary. Thereafter the patient has been treated with cyclophosphamide, doxorubicin, vindesine, prednisolone and etoposide every 3 weeks. This is our first case report of IBL-like T cell lymphoma associated with early gastric cancer.
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During surgery for intractable ventricular tachycardia, an ultrastructure of cardiac tissue was obtained from two male patients, 54 and 59 years old. On light microscopy, the histopathology was compatible with arrhythmogenic right ventricular dysplasia (ARVD). These myocardial samples were divided into three parts: an island of myocytes (some grouped cardiocytes floating on the fatty layer), a marginal zone (the parts of the myocardium surrounding the fatty infiltration), and a distant zone (as a control muscle). In the island of myocytes and marginal zone, myocardial hypertrophy, variability of cell diameter, degenerative changes of myocytes and interstitial fibrosis were more distinct than in the control zone. In addition, the number and diameter of intrasarcoplasmic lipid droplets detected among interstices of myofibrils also increased in both groups. The variability in number and diameter of the lipid droplets seemed to have a relation to the pathogenesis of fatty infiltration into the myocardium in ARVD. Lipid droplets were also revealed not only in the nuclei of myocytes but in the endothelial cells of capillaries and small vessels. Internuclear inclusion of the lipid was limited to the island and margin, but the lipid droplets in the endothelium spread widely in every zone. These lipid droplets are expected to have diagnostic value in the histological study of ARVD using endomyocardial biopsy.
In order to examine the proportional hazards assumption implicit in the proportional hazards model, three types of simulations were carried out on two groups of hypothetical survival data. Simulation 1 assumed that the hazard rate for one group was higher than that for the other group but that they were not proportional. Simulation 2 was an example of hazard rates crossing each other. Simulation 3 demonstrated the effect of the extent to which the hazard rates crossed. The test statistic, Z:PH, used for testing the proportional hazards assumption was calculated, along with the logarithm of the hazard ratio with its standard error. Although the increase in number of subjects was found to favor detections of violations of the proportional hazards assumption, cases such as those in Simulation 1 were considered acceptable for clinical use. Cases such as those in Simulation 2 were not suitable for the proportional hazards model. Simulation 3 suggested that cases with a substantial degree of unproportionality could be detected to violate the proportional hazards assumption, even when groups of 100 subjects each were involved in the analysis.
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We studied the multimeric composition of plasma von Willebrand factor (vWf) in 26 patients with chronic myelocytic leukaemia (CML); 13 in chronic phase, 8 in blast crisis, 5 in both chronic phase and blast crisis. The relative amount of large (multimer band greater than or equal to 11) multimers calculated by densitometer scan following SDS-agarose gel electrophoresis was 14.6 +/- 2.9% (mean +/- SD) in normal controls, 8.7 +/- 4.7% in chronic phase and 15.0 +/- 5.2% in blast crisis. CML patients in chronic phase (but not in blast crisis) had a significantly lower percentage of large multimers than normal controls (p less than 0.001). The relative amount of large multimers was positively correlated with a ratio of ristocetin cofactor/vWf antigen (p less than 0.005), and was negatively correlated with platelet count (p less than 0.001), WBC count (p less than 0.05) and granulocyte count (p less than 0.05). We conclude that some patients with CML, especially in chronic phase, lack large multimers. The negative correlation of the relative amount of large multimers with platelet and granulocyte count suggests that large multimers may be consumed in high platelet count states or degraded by protease(s) from increased blood cells.
It has recently been reported that a natural anticoagulant, protein S (PS), is depressed during oral anticoagulation. Since more detailed information is required from the clinical standpoint, we measured plasma levels of PS [both total and free (not complexed) PS antigen], C4b-binding protein (C4bp) and other vitamin K-dependent proteins (factors II, VII, IX, X and protein C) in 60 plasma samples from patients on long-term oral anticoagulant therapy with warfarin. Together with the reduction of other vitamin K-dependent plasma proteins, PS decreased during warfarin treatment, being dependent on the intensity of the therapy. A considerable variation in plasma PS levels was also observed among individuals with a similar intensity of anticoagulation. Plasma concentration of C4bp was closely correlated with total PS level, and free PS/total PS ratio was independent of thrombotest values. These findings indicate that long-term oral anticoagulant therapy results in the suppression of the synthesis of PS, and that its reduction is on the whole balanced with C4bp and vitamin K-dependent coagulation factors. It was suggested that the metabolism of C4bp might be regulated by the plasma PS level, although this hypothesis needs further exploration.