Biomedical subjects
Publications and source records attributed to T Sugihara.
A 41-year-old woman with umbilical endometriosis is presented. The umbilical lesion is repeatedly painful and there is a bloody discharge simultaneous with the menstrual period. Treatment of umbilical endometriosis is by excision. Hormonal therapy results in its incomplete regression. Umbilical endometriosis is a very rare disease, but should be considered in the differential diagnosis of umbilical tumors.
It is hypothesized that membrane-associated iron in the sickle red cell is of pathophysiologic importance, but the actual existence of such iron in the intact cell has been questioned. Using a strategy whereby membrane iron can be detected through its bioavailability for catalyzing peroxidation, we used phospholipid exchange protein to load membranes of intact erythrocytes (RBC) with approximately 2% phosphatidylethanolamine hydroperoxide (PEOOH) and monitored the development of peroxidation by-products during subsequent incubation. Normal RBC loaded with PEOOH developed very little peroxidation, but vitamin E-replete sickle RBC showed an exuberant peroxidation response that was not seen in cells loaded with control nonoxidized phosphatidylethanolamine. Ancillary studies of sickle RBC revealed that the catalytic iron included both heme iron and free iron located at the bilayer inner leaflet. Significantly, these studies also revealed that peroxidation after PEOOH loading is promoted by cellular dehydration and inhibited by hydration, thus identifying a dynamic interaction between hemoglobin (sickle >> normal) and membrane lipid. High-reticulocyte control RBC and sickle trait RBC behaved exactly like normal RBC, while HbCC RBC and RBC having membranes gilded with hemoglobin iron because of prior exposure to acetylphenylhydrazine showed an abnormal peroxidation response like that of sickle RBC. Indeed, the peroxidation response of RBC loaded with PEOOH paralleled amounts of iron measured on inside-out membranes prepared from them (r = 0.783, P < 0.01). These studies corroborate existence of membrane-associated heme and free iron in the intact sickle cell, and they document its bioavailability for participation in injurious peroxidative processes. That association of cytosolic sickle hemoglobin with membrane lipid is modulated by cell hydration status provides a mechanism that may help explain increased development of oxidative membrane lesions in abnormally dehydrated sickle RBC regardless of the mechanism underlying their formation.
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Twenty-seven patients with aplastic anemia (20 severe: 7 moderate) were treated with combined immunosuppression consisting of antilymphocyte globulin (ALG: Ahlbulin, Green Cross Co., Osaka, Japan) and high-dose methylprednisolone. Danazol or meptiostane was administered concurrently for at least 3 months. Ten of 27 patients had sustained improvement in hematopoiesis within 3 months of treatment. Three patients with hematological response had a recurrence of pancytopenia 12-36 months after the combined immunosuppressive therapy. Six patients died due to fungal pneumonia (2), hepatic failure (2), interstitial pneumonitis (1) and complication following allogeneic bone marrow transplantation (1). By life table analysis, the survival rate for all patients was 76 +/- 8% at 4 years, with 70 +/- 10% survival rate for patients with severe aplastic anemia and 100% for patients with moderate aplastic anemia. The factors predicting the good response to the therapy were a longer interval from diagnosis to the therapy and higher counts of platelet and reticulocyte at admission.
The authors report an 18-year-old female who developed severe hemolytic reaction and delayed neutrophil recovery after bone marrow transplantation (BMT) for aplastic anemia from her HLA-identical sibling. She had received much transfusion (61 units of red blood cells including 4 units of fresh whole blood from her parents and 350 units of platelets) for 12 years before BMT. To prevent graft rejection, she received an intensified preparative regimen consisted of cyclophosphamide 200 mg/kg followed by 5 Gy total body irradiation and 5 Gy total lymphoid irradiation. Prophylaxis for GVHD was short term methotrexate and cyclosporin-A. Despite of the removal of the red cells from the marrow, marked hemolytic reaction caused by antibodies directed to rh" (E) and hr' (c) red cell antigens was observed when rh" (E) and hr' (c) positive donor erythroid began to recover. The recovery of neutrophils, especially the fraction of segmented cells was also delayed. Flow cytometry showed that the serially collected patient's sera reacted to neutrophils derived from both patient's blood on the 64th post-transplant day and the donor's blood. The reactivity was strongest in pre-BMT sera. We conclude that residual antibodies sensitized before BMT are a major cause of these hematological problems.
Subtle peroxidative perturbation of normal red blood cells (RBC) using t-butylhydroperoxide creates a leak pathway for monovalent cations that is reversibly activated by cell deformation. To determine what factor promotes expression of this unique membrane defect, we have dissected "peroxidation" into components that can be evaluated separately by comparing K leak from suitably modified RBC during elliptical deformation and parallel control incubation. Selective introduction of phospholipid hydroperoxides into normal RBC membranes successfully induces a deformation-dependent leak pathway having the same phenomenology as that previously documented for cells treated with t-butylhydroperoxide itself (fully recoverable; calcium-independent; inhibited at lower pH; K efflux balanced by Na influx). This leak pathway occurs in the absence of detectable secondary peroxidative change and appears to reflect a direct influence of lipid hydroperoxide. Using micropipette examination of vesicular bilayers reconstituted from RBC lipid extracts, we find that lipid from peroxidized RBC exhibits only a slight tendency to be less cohesive than normal lipid, apparently precluding isolated lipid properties as an explanation for altered permeability barrier function. However, addition of a hydrophobic membrane-spanning peptide to these same lipids significantly diminishes bilayer cohesion, an effect that is exacerbated further by the presence of peroxidized lipid. These observations suggest that lipid hydroperoxide is a necessary, but perhaps not sufficient, factor for induction of this unique leak pathway. Our results may be relevant to the abnormal cation homeostasis of sickle RBC in which deformation of an oxidatively perturbed membrane occurs during the sickling phenomenon.
AP159 [N-cyclohexyl-1,2,3,4-tetrahydrobenzo(b)thieno(2,3c)pyridine]-3- carboamide,hydrochloride) showed clear anti-conflict activity in rats in the absence of effects on muscle relaxation, potentiation of anesthesia (in mice) or anticonvulsant activity (in mice). This anti-conflict effect was antagonized by treatment with Ro15-1788. By contrast with the deficits produced by diazepam, AP159 did not impair passive avoidance. The latter drug also improved scopolamine-induced amnesia in the same task. AP159 did not inhibit 3H-flunitrazepam binding, but potently inhibited 3H-8OH-DPAT binding. This compound increased serotonin and 5HIAA content of the midbrain raphe nuclei and of the amygdala centralis. AP159 has been shown to be a novel non-BZP anxiolytic agent with no side effects in laboratory animals; it could be a clinically effective anxiolytic agent.
Permanent tracheostomy and tracheoesophageal anastomosis were performed as a means of surgical intervention for the treatment of intractable aspiration pneumonia. Conventional methods of tracheoesophageal anastomosis have entailed various problems. The improved method devised by us uses the special histological features and enables safe and reliable anastomosis. By this method, the tracheal perichondrium is retained and the strength of the anastomosed portion of the trachea is maintained, the failure of sutures due to tension on the anastomotic site being prevented. Also, reanastomosis can be performed after the cure of primary disease.
For the interdigital space plasty to correct a syndactyly with fusion of the distal phalanges, we adopted a new operative procedure, covering the exposed distal bone with local rectangular flaps designed transversely on both dorsal and volar surfaces. A full-thickness skin graft from the groin region covers the remaining raw surface. The procedure was performed in six patients, and the flaps measured 6 mm (width) x 12 to 16 mm (length) in four patients, 5 x 15 mm in one patient, and 5 x 18 mm in one patient. Partial necrosis was observed in only one patient, in whom a narrow flap of 5 x 18 mm was used. In the other five patients, however, the results were satisfactory on both external appearance and function during the follow-up period of 3 to 6 years.
Thirty-six cases of cutaneous malignant melanoma with histologically involved lymph nodes were studied during a 2-10 year study period, and the characteristics of the metastasized nodes and the associated prognosis were compared. The results were as follows: 1) the survival rate in cases with 3 or fewer (n = 16) metastasized nodes was significantly higher than in cases with 4 or more positive nodes (n = 20); 2) the survival rate in cases in which metastasized nodes were limited to one regional lymph node section (n = 12) was significantly higher than in cases where metastasis extended to two or more intra-regional sections of nodes (n = 24); 3) cases which had nodes measuring 3.00 cm or less (n = 25) had significantly higher survival rates than those with nodes of 3.01 cm or more (n = 11). Therefore, the results indicate that the number of metastasized lymph nodes, the extension into regional lymph node sections, and the size of the metastasized lymph node(s) can be considered as important prognostic factors for melanoma patients.
Serum lipid levels of 168 women ranging in age from 30 to 69 were measured at a mass health screening in an urban community in Saitama prefecture. Degree of obesity, skinfold thickness and blood pressure were measured and the relation between these physical measurements to serum lipid levels was studied. The results are as follows: (1) Mean total cholesterol level, degree of obesity, systolic blood pressure and diastolic blood pressure increased linearly with advancing age. (2) Simple correlation analysis disclosed that the level of total cholesterol was positively correlated to age, degree of obesity, systolic blood pressure and triglyceride level. HDL-cholesterol level showed a significantly negative correlation to degree of obesity, skinfold thickness and triglyceride level. Degree of obesity was positively correlated to skinfold thickness, systolic blood pressure, diastolic blood pressure, total cholesterol and triglyceride level, but was negatively correlated to HDL-cholesterol. Systolic blood pressure had a positive correlation with age, degree of obesity, diastolic blood pressure, total cholesterol and triglyceride level. (3) Principal component analysis, when performed with the variables age, degree of obesity, skinfold thickness, systolic blood pressure, diastolic blood pressure, level of total cholesterol, triglyceride and HDL-cholesterol, showed that subjects could be divided into the group having obesity with low HDL-cholesterol (first principal component), the hypertensive group (second principal component), and the group having hyperlipidemia with advancing age (third principal component). (4) Multiple regression analysis was also carried out, taking HDL-cholesterol level as the dependent variable, and age, degree of obesity, systolic blood pressure, total cholesterol and triglyceride level as independent variables. Degree of obesity and triglyceride level were negatively related to HDL-cholesterol.
The clinical features and red cell membrane characteristics of 20 patients with hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA) were studied in relation to the effect of splenectomy. After splenectomy, anemia worsened and the extent of increased hemolysis in these patients was unchanged, indicating a contraindication for splenectomy. Concomitant with these results in clinical hematology, marked stomatocytic changes, increased red cell phosphatidylcholine content, and enhanced sodium transport, which were observed before splenectomy, were not improved by splenectomy.
A case of posterior tongue lymphoma associated with adult T-cell leukemia (ATL) that occurred as a lesion in the lingual dorsal portion is reported in a 64-year-old woman. Initially, a diagnosis of Hodgkin's lymphoma was considered as no findings associated with ATL except lymphadenopathy and serum anti-ATLA antibodies were present. Combined radiotherapy and chemotherapy were administered with favorable results; however, 4 months later, Pneumocystis carinii pneumonia developed, and 2 months later, generalized lymphadenopathy and hypercalcemia evolved. At this time, a diagnosis of ATL was made. The patient died of renal dysfunction 6 months after the initial presentation. In suspected cases of ATL and malignant diseases of T-cell lineage, namely, malignant lymphoma and mycosis fungoides, the presence of HTLV-1 infection should be confirmed by testing for anti-ATLA antibodies.
[1]Benzothieno[2,3-c]pyridines (10a-c, 11, 12a-t, and 13a,b) and 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines (3a-c, 7, 8a-c, and 9) were synthesized. The compounds are bioisosteres of beta-carbolines and 1,2,3,4-tetrahydro-beta-carbolines where the indole nitrogen is replaced by sulfur. Their pharmacological activity was evaluated in a water lick conflict test in rats and a passive avoidance test in mice. In the 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridine series, the presence of ethyl ester (3b) or cyclohexyl carboxamide (7) groups at C-3 conferred good anticonflict activity and lessening of memory impairment, while N-acylation of 3b abolished activity. In the [1]benzothieno(2,3-c]pyridine series, the aminoethyl carboxamide (12a) group at C-3 also conferred activity, but other amides studied were not active. The most potent compounds (3b, 7, and 12a) were also administered orally and had potent anticonflict and antiscopolamine amnesia-reversal activity. These compounds did not bind to the BZP receptor in spite of having structures similar to those of beta-carbolines. Compound 7 bound strongly to 5-HT1A receptors and would be expected to be a novel anxiolytic.
Intravenous administration of beta-CCM (methyl-beta-carboline-3-carboxylate) at doses ranging from 0.3 to 10 mg/kg dose-dependently inhibited muricide in olfactory bulbectomized rats. beta-CCM elicited a decrease of locomotor activity at doses ranging from 0.3 to 3 mg/kg, and it impaired rotarod performance at doses of 1 and 3 mg/kg. The inhibition of muricide induced by beta-CCM was antagonized by intraperitoneal administration of Ro15-1788 at 10 mg/kg or diazepam at 3 mg/kg. However, the hypolocomotor activity and impairment of rotarod performance induced by beta-CCM were not antagonized by diazepam at 3 mg/kg. These results indicated that beta-CCM exerts an inhibitory effect on muricide through benzodiazepine receptors and this inhibitory effect was not solely caused by its sedative or motor incordinating activity at the dose ranges used in this study.
The patient was a 64-year-old woman who was admitted to our hospital because of lumbago. A diagnosis of multiple myeloma (non-producing type) was made, based on (1) the presence of multiple osteolytic lesions, (2) hypercellular marrow with 64.2% plasmacytoid malignant cells, (3) no monoclonal gamma-globulin was detected in the serum and urine, and (4) abnormal monoclonal gamma-globulin was also not detected in the cytoplasm and membranes of these malignant cells. After several courses of chemotherapy, a pleural effusion infiltrated by myeloma cells developed and the patient's serum contained a markedly increased amylase activity of salivary-type. Amylase activity was also detected in vitro in the supernatant of cultured myeloma cells established from the patient's pleural effusion. The presence of alpha-amylase in the myeloma cells, which were derived from pleural effusion, was demonstrated immuno-histochemically. These observations indicates that amylase was ectopically produced by these myeloma cells. Interestingly, 14 out of 20 metaphases in the cells derived from pleural effusion showed translocation of 1p22 near the region of 1p21, where the amylase gene was assigned.
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Reported is a case of a malignant neuroepithelioma in the retroperitoneum. The patient was a 37-year-old male suffering from lumbago and edema of the lower extremities. After ultrasonography and a CT scan, a diagnosis of a retroperitoneal tumor was made and a surgical resection of the tumor was performed in October, 1985. The subsequent pathological diagnosis was malignant neuroepithelioma which showed epithelioid cell clusters that stained positively to NSE. Eleven months later, metastatic tumors were seen present in the lungs and the liver though they regressed markedly after adjuvant chemotherapy with ADM, CPM, and VCR. Forty-one months after his first operation, the patient continues to work. In this case, adjuvant chemotherapy has proved effective.