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Biomedical subjects

M Mukai

Publications and source records attributed to M Mukai.

At least 253 records · Page 14Linked to original sources

Regulation of T lymphocyte apoptosis. Signals for the antagonism between activation- and glucocorticoid-induced death.

Apoptotic death can be induced in T cell hybridomas by glucocorticoids or the stimulation via the TCR/CD3 complex. The two apoptotic processes are mutually antagonistic. We have previously proposed that positive selection of thymocytes for the formation of the T cell repertoire might be based on a similar mechanism. We analyzed the TCR/CD3-mediated signals essential for the regulation of apoptosis in T cell hybridomas. We suggest that both an increase in the intracellular Ca2+ level and an activation of protein kinase C are essential for the TCR/CD3-mediated apoptosis, because we obtained the following results: 1) either reduction of extracellular Ca2+ concentration or addition of a protein kinase inhibitor, 1-(5-isoquinolkinelsulfonyl)-2-methylpiperazine or N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide, inhibited anti-CD3-induced but not dexamethasone-induced DNA fragmentation. 2) The combination of ionomycin and PMA, but neither one alone nor the combination of ionomycin and cyclic nucleotide analogs, induced DNA fragmentation. On the contrary, we suggest that only an increase in the intracellular Ca2+ level is essential for the inhibition of glucocorticoid-induced apoptosis, because ionomycin alone as well as the combination of ionomycin and PMA inhibited dexamethasone- but not anti-CD3-induced DNA fragmentation.

Animals↗

Rapid isolation of plasmid DNA by LiCl-ethidium bromide treatment and gel filtration.

We established a simple and rapid plasmid DNA purification method. Crude plasmid DNA preparations are treated with 4 M LiCl in the presence of 0.6 mg/ml ethidium bromide to precipitate RNA and proteins contained in the DNA preparations. After removal of RNA and protein precipitates, the supernatant is filtered through a Sepharose CL6B column to remove low-molecular-weight contaminants. This procedure takes only 30 min and provides pure plasmid DNA preparations that consist mainly of covalently closed circular plasmid DNA but have no detectable RNA and protein. The purified DNA preparations are susceptible to various six- and four-base-recognition restriction endonucleases, T4 DNA ligase, the Klenow fragment of DNA polymerase I, and T7 and Taq DNA polymerase. Since no special equipment is needed for this purification method, 20 or more samples of microgram to milligram levels can be treated in parallel.

Chemical Precipitation↗

Leiomyosarcoma of the skin with generalized metastases: electron microscopic and immunohistochemical study.

A 62-year-old woman with numerous (more than 50) tumors between 25 and 75 mm in diameter disseminated over most of her body surface is reported. Biopsied tissue specimens demonstrated that the tumors consisted mainly of spindle-shaped cells with nuclear pleomorphisms and relatively high mitotic rates. They were irregularly arranged; they sometimes mimicked storiform- and palisading-patterns. Immunohistochemistry revealed that the tumor cells were positive for muscle-specific actin, desmin, and myosin, but negative for S-100 protein. Electron microscopy confirmed myofilaments and dense patches in the cytoplasm. The metastatic potential of such leiomyosarcoma of the skin is indicated.

Cytoskeletal Proteins↗

Serum requirement for in vitro invasion by tumor cells.

The effect of fetal calf serum (FCS) on in vitro invasion by rat ascites hepatoma cells (AH130) was studied by using the in vitro invasion assay. Although the coculture of the highly invasive clone (MM1) of AH130 cells and the mesothelial cell layer or endothelial cell layer in modified minimum essential medium supplemented with 10% FCS resulted in extensive penetration of the layer by the tumor cells, the omission of FCS resulted in an almost complete elimination of the in vitro invasion. The in vitro invasiveness by human small cell lung cancer cells (OC10) was also remarkably reduced by the omission of FCS from the assay medium, suggesting a requirement of serum for the in vitro tumor cell invasion. When 10% FCS was added to the medium 2 h after the tumor cell seeding in FCS-free invasion assay system, penetration by MM1 cells was observed within an hour. This rate of penetration was almost the same as that when 10% FCS was added at the time of tumor cell seeding. FCS was also required for the penetration of a mesothelial cell monolayer by MM1 cells in a defined growth medium (SFM-101), in which MM1 cells were well maintained. The invasion-inducing activity appears to be independent of the growth-stimulating activity in serum.

Animals↗

Giant cell fibroblastoma. A case report and immunohistochemical comparison with ten cases of dermatofibrosarcoma protuberans.

A 7-year-old boy with giant cell fibroblastoma (GCF) of the skin and subcutaneous tissue of the right chest wall is described. To date, the histogenesis of GCF has not been clarified. The reason for the diversity of immunohistochemical data among various authors may be because the specimens studied were from only part of the lesion, or reduction of antigenicity through the preparation process. However, our findings based on studies of many specimens from various parts of the tumor for accurate immunohistochemical evaluation suggest that GCF may be a myofibrohistiocytic tumor. Recently, the suggestion that GCF is a juvenile form of dermatofibrosarcoma protuberans (DFSP) has been reported. In addition to the present case, we performed immunohistochemical examination of 10 cases of definitely diagnosed DFSP for comparison. The immunohistochemical characteristics of these two neoplasms were concordant. However, from clinical and morphological viewpoints, it seems premature to recognize GCF as a juvenile form of DFSP.

Child↗

Long term effect of LDL apheresis in Japan. LDL Apheresis Study Group.

LDL-apheresis is introduced in many cases all over Japan. Among them, evaluation of long-term effect on ischemic heart disease (IHD) has made on 10 cases with homozygous familial hypercholesterolemia (FH) and 49 cases with heterozygous FH. As to homozygous FH, 3 patients had angina pectoris. Mean duration of treatment was 26 months (52 treatments). The changes in total cholesterol (TC) in each treatment was from 426 mg/dl to 151 mg/dl. Improvement in IHD was observed in 5 out of 10 cases. As to heterozygous FH, 17 cases had history of myocardial infarction and 12 had angina pectoris. Mean duration of treatment was 13 months (19 treatments). Mean TC was decreased from 271 mg/dl to 126 mg/dl by each treatment. Regression in Achilles tendon thickenting or skin and palpebral xanthomas was observed. Frequency of anginal attacks decreased in 8 out of 17 cases. Ischemic change in ECG were improved in 3 out of 26 cases. Coronary angiography performed with 2 to 3 years of interval in some cases revealed regression or no progression in coronary stenosis. As a whole, IHD improved in 15 cases and exacerbated in 2 cases. Main side effect was hypotension attack. Bradycardia and anginal attack during treatment were observed in some cases. LDL-apheresis was judged as effective in 25 out of 44 patients with IHD or xanthoma.

Blood Component Removal↗

[Superior vena cava syndrome as initial symptom of Vasculo-Behçet's disease--case report].

A 26-year-old woman with a history of recurrent spontaneous abortion was admitted because of superior vena cava syndrome. Chest computed tomography and digital subtraction angiography revealed obstruction of the superior vena cava by a thrombus. After admission she also developed oral aphthous ulceration, erythema nodosum, and positive cutaneous hypersensitivity reaction to intradermal injection of saline. Laboratory investigations revealed HLA-B51 and positive lupus anticoagulant. We made the diagnosis of Vasculo-Behçet's disease and treated her with heparin and urokinase with no clinical improvement. The fever subsided after prednisolone administration. Two years later, superior vena cava syndrome had slightly improved, although RI venography showed complete obstruction of the superior vena cava with development of collateral circulation. Endoscopic examination showed downhill esophageal varices. It is of note that the initial symptom in this case of Vasculo-Behçet's disease was superior vena cava syndrome, and that lupus anticoagulant may have contributed to the thrombus formation.

Adult↗

[A case of pulmonary eosinophilic granuloma diagnosed by TBLB].

A case of pulmonary eosinophilic granuloma which was diagnosed by TBLB was presented. A 24-year-old male was admitted complaining of cough and fever of unknown etiology. He had a history of fever which had disappeared spontaneously 9 months previously. Laboratory examinations including blood gas analysis and pulmonary function tests showed no significant abnormalities. Chest roentgenogram showed faint linear opacities. Computed tomography revealed multiple small cysts and small nodular lesions mainly in the upper lung field. CT findings were strongly suggested pulmonary eosinophilic granuloma. TBLB was performed and 6 specimens were obtained, of which 4 showed granulomatous lesions consisting of histiocytosis X cell and inflammatory cells with infiltration of eosinophils. Furthermore, granulomatous lesions were positive for S-100 protein staining. The effectiveness of open lung biopsy has been emphasized in the diagnosis of pulmonary eosinophilic granuloma, however, TBLB is also useful for diagnosis, especially in the active or early stage of this disease.

Adult↗

Intracavitary drainage procedure for giant bullae in compromised patients.

Two cases of giant bullae were treated by intracavitary suction and drainage procedure under local anesthesia because of the poor pulmonary function. After staged bullectomy, the patients returned to normal life. The first case was admitted to our intensive care unit (ICU). Tube drainage was performed in the giant bulla of the left lung immediately after admission. One month after recovery from right heart failure and mediastinal shift to the right side, bullectomy was performed using linear stapler. The patient was discharged 20 days later. The second case was admitted with severe dyspnea and bilateral giant bullae were noticed. We performed tube drainage for larger bulla of the left lung under local anesthesia. Two months later, bullectomy was performed on the right side, because the bulla on the left side became smaller and the general condition of the patient improved. The patient was discharged three months later on foot and has since been asymptomatic. Giant bulla is a well-established clinical entity which includes abnormal dilatation of various parts of the tracheo-bronchial tree and other discrete sacs originating from the interstitial portion of the lung. Giant bullae are frequently associated with marked dyspnea and emphysematous symptoms. However, these symptoms depend upon various factors: size, location, valvular mechanism, condition of the contiguous lung parenchyma and the changes that may take place in the intrathoracic pressure.

Aged↗

[The production of monoclonal anti-human spectrin antibody cross-reactive with single-stranded DNA].

Five monoclonal anti-human red blood cell (RBC) antibodies (all IgM kappa type) were produced by immunizing BALB/c mouse with human O-type RBC. Solid phase enzyme linked immunosorbent assays (ELISAs) were used for studying the reactivities of monoclonal antibodies against RBC, DNA, cardiolipin, dermatan sulfate and spectrin. Because two monoclonal antibodies (1B1A2E5, 1B1B2G7) of these antibodies also reacted with heat-denatured DNA (ssDNA) derived from calf thymus, salmon sperm and human white blood cell, the cross-reactivities of two monoclonal antibodies were analyzed. They reacted with spectrin, one of the RBC cytoskeleton proteins, by western blotting using RBC ghost protein and ELISA using spectrin, but not react with other anionic antigens such as cardiolipin and dermatan sulfate. The anti-RBC activities of the two monoclonal antibodies were not changed by DNase I treatment, but were decreased by pronase E treatment of RBC ghost protein. And, the anti-ssDNA activities of these antibodies were abolished by DNase I treatment, but were not changed by pronase E treatment of DNA. The reactivities of these antibodies to RBC and ssDNA were inhibited by ssDNA, The reactivities of these antibodies to RBC and ssDNA were inhibited by ssDNA, RBC ghost protein and rabbit anti-mouse IgM antiserum, but were not inhibited by dsDNA, RBC, rabbit anti-mouse IgG antiserum, bovine serum albumin and spectrin in liquid phase. In inhibition test, spectrin in liquid phase did not inhibit the reaction for RBC or ssDNA of these antibodies. Complements were fixed to these antibodies in RBC, ssDNA and spectrin ELISA. In the view of the above results, it was concluded that the RBC antigen of the 2 monoclonal antibodies was directed against spectrin in solid phase, and that these antibodies were cross-reactive with both RBC (spectrin) and ssDNA (derived from calf thymus, salmon sperm and human white blood cell).

Animals↗

[A case of rheumatoid arthritis developing pemphigus-like skin lesion during treatment with bucillamine].

Bucillamine is a useful medication for treatment of rheumatoid arthritis (RA) but some patients develop side effects from it. Here, we report a patient with RA developing a pemphigus-like skin lesion during treatment with bucillamine. A 55 year old woman with RA (stage III, class II) had been treated with bucillamine in our hospital since September 1988. Her symptoms of RA had gradually improved after administration of bucillamine but the generalized skin rash with itching developed in June 1989. Skin biopsy revealed spongiosis, the infiltration of lymphocytes in the epidermis and inter-cellular deposition of IgG. These findings were consistent with the histological change of pemphigus. Since symptoms of the skin disappeared two months later after the discontinuation of bucillamine. We considered that her pemphigus-like lesion was induced by this drug. D-penicillamine is one of the drugs which induce pemphigus. Though the mechanisms of this side effect have not been clear, it is thought that autoantibody induced by D-penicillamine could be one of the cause of pemphigus. Because the chemical structure of bucillamine is similar to that of D-penicillamine, the autoimmune mechanisms may also play a role in the onset of the pemphigus-like lesion in this case.

Anti-Inflammatory Agents, Non-Steroidal↗

[Significance of radionuclide examination in hepatic arterial infusion chemotherapy using implantable reservoir].

Technetium 99m macroaggregated albumin (Tc-MAA) perfusion scintigraphy has been performed during hepatic arterial infusion chemotherapy using implantable reservoir. A total of 40 radionuclide (RI) studies were performed on 25 patients with liver metastasis of colorectal origin. Of 40 RI studies, 12 (30%) showed impaired liver perfusion. Three studies showed no perfusion of the liver, 3 increased radiotracer accumulations at liver hilus, 2 extrahepatic distributions, 2 catheter occlusions, 1 extravasation and 1 unilobar distribution. The accumulation of Tc-MAA in the tumor was graded from Grade I (tumor uptake decreased or similar relative to liver) to Grade III (tumor uptake remarkably increased). The response to chemotherapy was evaluable in 14 cases. A case with Grade I resulted in NC. Of 6 cases with Grade II, 1 resulted in MR, 3 in NC and 1 in PD. Of 8 cases with Grade III, 2 resulted in PR, 1 in MR and 5 in NC. Tumor response was observed in cases showing increased uptake of Tc-MAA. SPECT was performed in 7 cases, and revealed that hepatic tumors were hypervascular. We concluded that RI examination reveals not only hepatic perfusion, but also tumor microcirculation.

Antineoplastic Agents↗

Ca(2+)-dependent suppression of inwardly rectified K+ channels in rat basophilic leukemia cells.

A patch clamp technique was used in rat basophilic leukemia (RBL) cells to reveal the response properties of K+ Channels at different membrane potentials and the effects of Ca2+ on channel activity. In the whole-cell, cell-attached and inside-out clamp configurations, inward K+ currents markedly increased with increasing hyperpolarization, showing the inwardly rectifying property of the currents. Mean amplitude of inward K+ currents was smaller with larger (1-10 microM) internal Ca2+ than with low (less than or equal to 100 nM) internal Ca2+, indicating that high concentrations of internal Ca2+ suppress channel activity. Single channel currents and the conductance of channels were not changed by high internal Ca2+ concentrations, but the open probability of the channels was decreased in these conditions. The results suggest that, by changing K+ channel activity, Ca2+ is a factor in the regulation of inwardly rectified K+ currents in RBL cells.

Animals↗

[Thermography of collagen diseases with Raynaud's phenomenon].

In forty-four patients with collagen diseases accompanied with Raynaud's phenomenon(systemic lupus erythematosus(SLE)10, progressive systemic sclerosis(PSS)15, primary Sjögren's syndrome(PSJS)18 and mixed connective tissue disease(MCTD)1), we analyzed the thermography of fingers after thermal stimulation with cold water(15 degrees C, 30 seconds). In normal controls, the temperature of the distal points of fingers was higher and recovered more quickly than that of the proximal points(proximal interphalangeal joint; PIP). But in the patients with Raynaud's phenomenon, the temperature of distal point of fingers was lower and recovered more slowly than that of proximal points. Because the difference of the temperature between the distal and the proximal points (DP)is a good parameter to distinguish these two thermographic patterns, we analysed DP. DP is less influenced by room temperature than the temperature of fingers and the recovery temperature after thermal stimulation which have been used as indicators of Raynaud's phenomenon. DP in the normal controls was significantly higher than that in the patients. DP in PSS was lower than that in SLE and PSJS, and statistically associated with the markers of disease activities, such as erythrocyte sedimentation rate, titers of anti-RNP antibody and diffusing capacity of lung. These results show that thermographic pattern and the value of DP are the useful indicator of severity of Raynaud's phenomenon.

Adult↗

[Pneumoperitoneum without perforation of the gastrointestinal tract in a patient with systemic lupus erythematosus].

Pneumoperitoneum often occurs after the perforation of the gastrointestinal tract. However, pneumoperitoneum without the perforation has been reported as one of the complications of collagen diseases, the cause of which is usually the rupture of pneumatosis cystoides intestinalis (PCI). PCI is sometimes observed in the patients with scleroderma and mixed connective tissue disease but rarely in the patients with systemic lupus erythematosus. We reported here a case of systemic lupus erythematosus developed the pneumoperitoneum without the perforation of gastrointestinal tract. A 51-year-old female who had been diagnosed as systemic lupus erythematosus and taken steroid for 12 years, visited our hospital because of general malaise. She had no abdominal symptoms but the roentgenographic examinations revealed the pneumoperitoneum. The laparotomy was performed and there were no findings of the perforation of the gastrointestinal tract. Because PCI is hardly recognized macroscopically after the rupture and the pneumoperitoneum due to PCI is often asymptomatic, we considered the cause of the pneumoperitoneum in this case was the rupture of PCI. The mechanisms of the formation of PCI in patients with collagen diseases were also discussed in this paper.

Female↗

Solid, infiltrating variety of papillary cystic neoplasm of the pancreas.

Four tumors with histologic, histochemical, and ultrastructural characteristics of papillary cystic neoplasm of the pancreas but lacking the capsule commonly observed in papillary cystic neoplasm and infiltrating interiorly into the pancreatic parenchyma were seen in two men and two women who were 39 to 51 years old. These tumors contrasted with typical encapsulated papillary cystic neoplasms that show extrapancreatic growth and that are detected as a palpable abdominal mass in young women. These four tumors, although unpalpable, were all detected by nodular images of calcification in abdominal plain radiography. The tumors had a mean diameter of 3.1 cm (range, 1.7 to 4.5 cm), were confined within the pancreatic parenchyma, and showed central fibrosis accompanied by dystrophic changes such as calcification and ossification. A small necrotic cyst contiguous to the fibrous focus also was observed in the tumor in three patients. Tumor cells similar to those of a papillary cystic neoplasm had infiltrated among the pancreatic parenchyma in solid and pseudopapillary patterns, and pleomorphic atypism was observed in some parts of the tumor in three patients. These tumors were tentatively designated solid, infiltrating variety of papillary cystic neoplasms to differentiate them from ordinary encapsulated papillary cystic neoplasms. Although no signs of recurrence have been noticed after surgical treatment in these patients, the infiltrating growth pattern and the presence of pleomorphic atypism suggest higher malignancy than the ordinary papillary cystic neoplasm. The contrasting growth pattern and possible malignancy may warrant establishment of these tumors as a papillary cystic neoplasm subclass.

Adult↗

Potentiation of invasive capacity of rat ascites hepatoma cells by adriamycin.

The effect of Adriamycin on the invasive capacity of rat ascites hepatoma cells, W1, was studied. The invasive capacity of W1 cells was estimated in vitro by counting the number of penetrated single tumor cells and tumor cell colonies formed from the penetrated cells underneath a cultured mesothelial cell monolayer (H. Akedo et al., Cancer Res., 46: 2416-2422, 1986). A considerable increment of the invasive capacity was observed when the tumor cells had been treated with 1.0 to 20.0 microM Adriamycin. This augmentation of invasive capacity of tumor cells was partially inhibited by 60 microM N-acetylcysteine, a scavenger of free radicals. On the other hand, 60 microM N-acetylcysteine did not impair the cytotoxicity of Adriamycin for W1 cells measured by an in vitro tetrazolium-based colorimetric assay for cytotoxicity.

Acetylcysteine↗

[New combined therapy of radiation and local administration of OK-432 for esophageal cancer--local control rate and two-year survival rate].

We devised new combination therapy of radiation and local administration of OK-432 and performed for 26 patients with esophageal cancer between March, 1987 and December, 1988 as a pilot study. The average age was 73 years. Among 26 patients, male were 20 and female were six. Patients were irradiated at the schedule of under 2 Gy/day and the dose of TDF (time, dose and fractionation factor) 100 totally. OK-432, 10KE was endoscopically administered around cancer lesion at the beginning of the radiotherapy, and two weeks later, 5KE was given in the same manner. Complete response was obtained 20 out of 26 cases (77%) and partial response was obtained in the remaining six cases (23%). All six patients with tumor length less than five cm showed complete response. All 16 patients who could not eat food orally before treatment, became to take food enough orally after the treatment and could discharge in good condition. One year and two years survival rate of 26 patients by Kaplan Meier method were 67.4% and 47.2%, respectively. Six patients with tumor length less than five cm, are all alive without a sign of recurrence. This combination therapy will improve not only the response rate and the survival rate, but also the quality of life of patients with esophageal cancer.

Aged↗