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T Kasugai

Publications and source records attributed to T Kasugai.

At least 19 recordsLinked to original sources

BALB/3T3 fibroblast-conditioned medium attracts cultured mast cells derived from W/W but not from mi/mi mutant mice, both of which are deficient in mast cells.

Proliferation of murine mast cells is induced by both T-cell-derived and fibroblast-derived growth factors. Because the most potent T-cell-derived mast cell growth factor, interleukin-3, promotes the migration of mast cells, we investigated whether fibroblast-derived growth factors had the chemoattractive activity as well. Conditioned medium (CM) of BALB/3T3 fibroblasts induced the migration of cultured mast cells (CMC) derived from normal (+/+) mice. BALB/3T3-CM contained the mast cell growth factor (MGF)/stem cell factor (SCF)/kit ligand (KL), which is the ligand for the receptor encoded by the W (c-kit) gene. CMC derived from the spleen of W/W mice lack the extracellular domain of the W (c-kit) receptor, and W/W CMC did not proliferate in response to BALB/3T3-CM. However, W/W CMC did migrate normally toward BALB/3T3-CM and, moreover, the antibody to the extracellular domain of the W (c-kit) receptor did not inhibit the chemoattractive activity of +/+ CMC toward BALB/3T3-CM. These results indicated that MGF/SCF/KL itself did not represent the major chemoattractive activity. On the other hand, BALB/3T3-CM induced neither proliferation nor migration of CMC derived from mi/mi mice. Both W/W and mi/mi mice are deficient in mast cells, but the present results suggest that the mechanism of the abnormality is different between W/W and mi/mi mice.

Animals

c-kit Gene was not transcribed in cultured mast cells of mast cell-deficient Wsh/Wsh mice that have a normal number of erythrocytes and a normal c-kit coding region.

The Wsh is a mutant allele at the W (c-kit) locus of mice. Mice of Wsh/Wsh genotype have white hairs and black eyes. Although adult C57BL/6-Wsh/Wsh mice were not anemic, they showed a remarkable depletion of mast cells. Most homozygous or double heterozygous mutant mice at the W (c-kit) locus, of which mast-cell depletion was comparable to that of Wsh/Wsh mice, are deficient in germ cells. However, male and female Wsh/Wsh mice have an appreciable number of germ cells in their gonads. We investigated the mechanism of specific depletion of mast cells in Wsh/Wsh mice. Cultured mast cells (CMC) derived from the spleen of Wsh/Wsh mice neither attached to normal (+/+) fibroblasts nor survived in the coculture with +/+ fibroblasts. The c-kit messenger RNA (mRNA) was strongly expressed in +/+ CMC, but not detectable in Wsh/Wsh CMC. Despite the lack of c-kit mRNA in Wsh/Wsh CMC, the c-kit mRNA was normally detectable in the cerebellum and weakly detectable in the testis and spleen of Wsh/Wsh mice. No significant changes were found in the nucleotide sequence of the c-kit transcripts obtained from the cerebellum of Wsh/Wsh mice. Development of mast cells, erythrocytes, and germ cells in Wsh/Wsh mice appeared to be parallel with the magnitude of the c-kit gene expression in each cell type.

Anemia

Low c-kit expression of cultured mast cells of mi/mi genotype may be involved in their defective responses to fibroblasts that express the ligand for c-kit.

Mutant mice of mi/mi genotype are osteopetrotic and deficient in tissue mast cells due to a defect in osteoclasts and mast cells. In an effort to further understand the mechanisms behind why mi/mi mouse-derived cultured mast cells (mi/mi-CMC) responded to interleukin-3 (IL-3), but not to the proliferative stimuli presented by fibroblasts, mi/mi-CMC and congenic normal (+/+) mouse-derived CMC (+/+-CMC), both of which expressed the phenotypic characteristics of immature mast cells, were cocultured with Swiss albino/3T3 fibroblasts in a medium containing IL-3. In the in vitro CMC/fibroblast coculture, mi/mi-CMC did not acquire the phenotypes of connective tissue-type mast cells (CTMC), while +/+-CMC did. In addition, attachment of mi/mi-CMC to the fibroblasts was found to be significantly lower than that of +/+-CMC. Because the interaction of c-kit product with its ligand (stem cell factor [SCF]) is known to play an important role not only in proliferation and differentiation of mast cells but also in attachment of CMC to fibroblasts, the expression and function of c-kit were investigated in mi/mi-CMC and +/+-CMC. Recombinant rat SCF (rrSCF164) induced a dose-dependent proliferation of +/+-CMC. Also, rrSCF164 induced +/+-CMC to acquire the phenotypes of CTMC in the medium containing IL-3. By contrast, rrSCF164 did not stimulate the proliferation of mi/mi-CMC nor induce a phenotypic change of the cells from immature mast cells to mature, CTMC-like mast cells. Immunoblotting with antiphosphotyrosine antibody showed that rrSCF164 induced considerable tyrosine phosphorylation of 145- to 165-Kd protein, the product of c-kit, in +/+-CMC, whereas tyrosine phosphorylation of the protein was barely detectable in mi/mi-CMC. Northern blot and flow cytometry analyses showed that mi/mi-CMC expressed much less c-kit at both protein and message levels than +/+-CMC. Further, mi/mi-CMC were found to differ from +/+-CMC in the expression of mouse mast cell protease-6 (MMCP-6) and MMCP-2 messenger RNA transcripts. These results suggest that the gene product of the mi locus may be important in regulating the expression of gene products such as c-kit, and that mast cell deficiency of mi/mi mice appears to be due, at least in part, to impaired signaling through the c-kit receptor because of the low c-kit expression.

3T3 Cells

Necessity of extracellular domain of W (c-kit) receptors for attachment of murine cultured mast cells to fibroblasts.

The receptor encoded by the W (c-kit) locus (W receptor) is expressed on the surface of cultured mast cells (CMC) derived from normal (+/+) mice, whereas its ligand encoded by the Sl locus (Sl ligand) is expressed on the surface of fibroblast cell lines derived from murine embryos. Involvement of W receptors and Sl ligands in attachment of CMC to fibroblasts was investigated. CMC were cocultured with fibroblasts; nonattaching CMC were removed and the remaining CMC were counted. CMC derived from mice of the W/W genotype did not express the extracellular domain of W receptors, and attachment of W/W CMC to +/+ fibroblasts was significantly impaired. Fibroblasts derived from embryos of the Sl/Sl genotype did not express Sl ligands, and the attachment of +/+ CMC to Sl/Sl fibroblasts was also impaired. The Wv and W42 alleles are point mutations at the intracellular tyrosine kinase domain. Attachment of either Wv/Wv, W/Wv, or W/W42 CMC to +/+ fibroblasts was comparable with that of +/+ CMC. Moreover, the addition of monoclonal antibody against the extracellular domain of W receptors inhibited the attachment of +/+ CMC to +/+ fibroblasts. Thus, the extracellular domain of W receptors appeared to be necessary for attachment of CMC to fibroblasts.

Alleles

Anemia and mast cell depletion in mutant rats that are homozygous at "white spotting (Ws)" locus.

Mice possessing two mutant alleles at the W or Sl locus are anemic and deficient in mast cells. These mouse mutants have black eyes and white hair. Because homozygous mutant rats at the newly found white spotting (Ws) locus were also black-eyed whites, the numbers of erythrocytes and mast cells were examined. Suckling Ws/Ws rats showed a severe macrocytic anemia and were deficient in mast cells. When bone marrow cells of normal (+/+) control or Ws/Ws rats were injected into C3H/He mice that had received cyclophosphamide injection and whole-body irradiation, remarkable erythropoiesis occurred in the spleen of +/+ marrow recipients but not in the spleen of Ws/Ws marrow recipients. When skin pieces of Ws/Ws embryos were grafted under the kidney capsule of nude athymic rats, mast cells did develop in the grafted skin tissues. Therefore, the anemia and mast cell deficiency of Ws/Ws rats were attributed to a defect of precursors of erythrocytes and mast cells. Because the magnitude of the anemia decreased and that of the mast cell deficiency increased in adult Ws/Ws rats, this mutant is potentially useful for investigations about differentiation and function of mast cells.

Anemia

Left atrial myxoma metastasizing to the aorta, with intraluminal growth causing renovascular hypertension.

The first case of 'a metastatic intraluminal myxoma of the aorta' is reported. The patient was a 48-year-old man who had already developed metastases to his skin and brain from a left atrial myxoma. Then, his myxoma grew in his leg and intraluminally in the aorta and caused renovascular hypertension. Surgical removal of the tumor could relieve his hypertension, but he finally died 6 months after surgery. The findings at autopsy were described and previous reports on metastasizing left atrial myxomas were also reviewed.

Aorta, Abdominal

Fibroblast-dependent differentiation/proliferation of mast cells.

Fibroblast-dependent differentiation and proliferation of mast cells were reviewed from the viewpoint of mast cell-deficient mutant animals. Mice of W/Wv, Sl/Sld or mi/mi genotype are deficient in mast cells. However, since T cell-dependent differentiation and proliferation of mast cells are intact in these mutant mice, mast cells do develop when bone marrow cells of these mutant mice were cultured in the presence of T cell-derived growth factors. Cultured mast cells (CMC) of W/Wv mice cannot receive the proliferative stimulus from fibroblasts whereas fibroblasts derived from Sl/Sld embryos cannot provide normal (+/+) CMC with the proliferative stimulus. The W locus encodes a tyrosine kinase receptor and the Sl locus the ligand for the receptor. Although +/+ CMC acquire the phenotype resembling connective tissue-type mast cells when cocultured with fibroblasts in medium containing T cell-derived growth factors, mi/mi CMC do not. We recently found a mast cell-deficient mutant of rats. Biological features of the mast cell-deficient rats were very similar to those of W/Wv mice. The mast cell-deficient mutant animals are invaluable tools for investigations of differentiation/proliferation and functions of mast cells.

Animals

[Primary operation of pericardiectomy and decortication of the right lung for tuberculous pericarditis with empyema].

A 28-year old man who complained of ortho-apnea and fever was diagnosed to have cardiac tamponade. Pericardiocentesis was immediately carried out and peri-cardiac window was created on the 11th day. Typical caseating granulomas with acid-fast bacilli were detected in sections of the pericardium. A positive culture of Mycobacterium tuberculosis was observed in the sputum and the pericardial fluid. Though 3-month anti-tuberculosis treatment with streptomycin, isoniazid, and rifampicin was continued with 6-week steroid therapy, progressive thickness of the pericardium was suggested subsequent constriction. Pericardiectomy for pericarditis and decortication for empyema in the right thorax was performed at the same time. After 10 x 12 cm pericardium was resected through median sternotomy, decortication of the right lung was performed through right posterolateral thoracotomy. In the case with thickened pericardium, early pericardiectomy is recommended.

Adult

[Preservation of pulmonary function by chest wall reconstruction].

Thirteen mongrel dogs were resected 4 ribs with surrounding tissue. Eight dogs had the chest wall closed by skin alone, and in five animals, the chest wall reconstructed by a polyethylene mesh or marlex sandwich. In the latter PaO2 was significantly higher than that of animals not undergoing reconstruction 3 days after operation. Pulmonary function was appeared to be preserved by reconstruction. Clinically, 68 cases underwent chest wall resection and in 28 cases, defects were reconstructed. Although only portions of 1 or 2 ribs were resected in the non-reconstructed cases, VC, FEV1, and TLC significantly dropped post-operatively. In the reconstructed cases, VC significantly dropped postoperatively. Post-operative complications occurred in 3.6% of the reconstructed cases and in 9.8% of the non-reconstructed cases. Since only 1 rib resection led to reduced ventilatory function clinically, reconstruction for small chest wall defects appears advisable for maintaining pulmonary function.

Adolescent

Mechanism of mast cell deficiency in mutant mice of mi/mi genotype: an analysis by co-culture of mast cells and fibroblasts.

Mutant mice of mi/mi genotype are osteopetrotic and are deficient in mast cells. The osteopetrosis of mi/mi mice can be cured by bone marrow transplantation from congenic normal (+/+) mice, and therefore, the cause of the osteopetrosis is attributed to a defect of osteoclasts. Since both osteoclasts and mast cells are the progeny of multipotential hematopoietic stem cells, we examined whether mast cells were defective in mi/mi mice. In spite of the deficiency of mast cells in tissues of mi/mi mice, mast cells did develop when spleen cells of mi/mi mice were cultured with pokeweed mitogen-stimulated spleen cell conditioned medium (PWM-SCM). The proliferative response of cultured mast cells (CMC) derived from mi/mi mice to PWM-SCM was comparable with that of CMC from +/+ mice. In contrast, when CMC were co-cultured with the NIH/3T3 fibroblast cell line in culture medium lacking PWM-SCM, only +/+ CMC entered into the S phase of the cell cycle and were maintained; mi/mi CMC gradually disappeared. Moreover, fibroblasts derived from the skin of mi/mi mice normally supported the proliferation of +/+ CMC. Thus, the mast cell deficiency of mi/mi mice appears to be due to the inability of mi/mi mast cells to respond to the proliferative stimulus presented by fibroblasts.

Animals

Pathological findings of the aortic homograft in a patient with tetralogy of Fallot twenty years after implantation.

We report pathological findings of the aortic homograft in a 27-year-old patient who died 20 years after implantation at the time of correction of tetralogy of Fallot. Although calcification of the homograft was severe with degeneration of valve leaflets, no functional obstruction of the homograft was found as a conduit. This observation may suggest a beneficial aspect of the aortic homograft as the right ventricle to the pulmonary artery conduit late after corrective surgery even if calcification was not avoided.

Adult

Sequential malignant transformation of cardiac myxoma.

We describe a case of cardiac myxoma in a 44-year-old Japanese man, who died after developing metastases in the skin, brain and muscle. A satellite tumor which was attached to the wall of the abdominal aorta induced marked hypertension due to obstruction of the renal arteries. Although the primary heart tumor had typical histological features of benign cardiac myxoma, the recurrent heart tumor, which was partly resected three months before the patient's death, showed apparently malignant characteristics resembling malignant fibrous histiocytoma (MFH). Since the histological features of the initial and recurrent tumors were different, the grade of malignancy was investigated using the cellularity of the tumor as an arbitrary criterion. A gradual but significant increase in the cellularity was observed over the course of five years. Immunohistochemically, tumor cells in the muscle metastasis contained vimentin and factor VIII-related antigen, and multinucleated giant cells in the recurrent heart tumor contained desmin, which is rarely detectable in MFH. Therefore, we considered that the present case represented malignant transformation of benign cardiac myxoma.

Adult

Crystalline light-chain deposition and amyloidosis in the thyroid gland and kidneys of a patient with myeloma.

A 48-year-old Japanese woman died of multiple myeloma (lambda light-chain type) with chronic renal failure. Histological examination revealed deposition of a homogeneous substance and crystals in the kidneys and thyroid gland. The homogeneous substance was stained with Congo red after permanganate treatment but did not stain with antibody to amyloid A protein, and it was recognized as AL-type amyloid. Crystals were not stained with Congo red, but crystals were stained with antibody to the lambda light chain. Since AL-type amyloid is considered to be derived from a myeloma light chain, the present case showed two different types of deposition, both of which were derived from the same myeloma protein.

Amyloid

Regulation of mast cell differentiation studied using the diffusion chamber technique.

A homogeneous population of mast cells was obtained by culturing bone marrow cells of WBB6F1(-)+/+ mice. The proliferation of the cultured mast cells in diffusion chambers was investigated to examine whether the diffusion chamber technique was applicable for study of the regulation of mast cell proliferation. WBB6F1-W/Wv mice are genetically deficient in mast cells. When cultured mast cells of WBB6F1(-)+/+ mouse origin were directly injected into the peritoneal cavity of WBB6F1-W/Wv mice, the mast cells survived. In contrast, WBB6F1(-)+/+ mouse-derived cultured mast cells did not survive in diffusion chambers implanted in the peritoneal cavity of either WBB6F1-W/Wv or WBB6F1(-)+/+ mice. Because the coinoculation of NIH/3T3 cells supported the proliferation of mast cells in diffusion chambers, a certain type of cells in the peritoneal cavity appeared to have the same mast cell-supporting activity as NIH/3T3 cells. The magnitude of either interleukin 3-dependent or NIH/3T3 cell-dependent proliferation of mast cells in diffusion chambers was not significantly influenced by the genotype of chambers recipients (i.e., WBB6F1(-)+/+ or WBB6F1-W/Wv mice), suggesting that the previously reported inhibitory effect of mast cells on differentiation of mast cells may be mediated by direct contact between mast cells.

Animals

[An unresectable gastric cancer radically resectable following UFT, ADM, MMC therapy].

A 58-year-old woman who was inoperable because of S3 (pancreas and colon) and P1 at the initial operation was treated with UFT, ADM and MMC at a dosage of 242.7 g, 418 mg and 166 mg, respectively. After the chemotherapy (2 years and 6 months from initial operation), a second look operation revealed that a tumor was localized in the submucosal layer and there were no lymph node metastases. Thus, it could be resected radically. Until now, various methods of chemotherapy for unresectable gastric cancer have been reported, and many cases of CR contained fluoropyrimidine derivates. In the case under study, combination chemotherapy containing UFT was performed with good results.

Adenocarcinoma

[A primary gastric adenosquamous carcinoma with remarkable lymphatic metastasis diagnosed by the stomach and lymph node biopsy].

This report describes the case of a 74-year-old female, who had been admitted to hospital because of epigastralgia and appetite loss. An ultrasonogram and a CT scan of the abdomen revealed a remarkable lymph node metastasis. Through an upper gastrointestinal tract (UGI) X-ray, a Borrmann III type gastric carcinoma was detected. Under endoscopic guidance, a gastric and a lymph node specimen were taken and biopsied, revealing a keratinous, well-differentiated squamous cell carcinoma and a poorly differentiated adenocarcinoma, leading to a diagnosis of a primary gastric adenosquamous carcinoma with a remarkable lymphnode metastasis. After chemotherapy, a CT scan, a UGI X-ray, and an endoscopic examination revealed distinct tumor reduction.

Adenocarcinoma

[Indications and limitations of laser treatment for early gastric cancer and palliative treatments for malignant obstruction of the esophagus and stomach].

The long-term effect of endoscopic laser treatment for early gastric cancer as a local curative procedure was reported. Forty-seven patients with endoscopically diagnosed early gastric cancer whose surgical risk was critical or who refused surgery were treated by either photocoagulative Nd: YAG laser (YAG) or photodynamic therapy (PDT) with argon dye laser and hematoporphyrin derivatives (HpD) or both and followed-up for more than 3 years. Thirty-one patients were initially treated by YAG. One patient was lost to follow-up. Sixteen of 30 cases (53%) treated by YAG were negative for cancer on biopsy for 9 to 73 months (mean 3 years and 7 months) after the initial treatment. Sixteen cases were initially treated by PDT. Eight of 14 cases (57%) treated by PDT with argon dye laser were negative for cancer on biopsy for 19 to 35 months (mean 1 year and 7 months). Ten of 13 cases treated by combined laser therapy were negative for cancer on biopsy for 12 to 77 months (mean 3 years and 2 months). Curative effect of YAG and PDT was expected in lesions of superficially elevated mucosal cancer (type) IIa less than 20mm and well demarcated superficially depressed mucosal cancer (type IIc) less than 10mm. PDT was superior to YAG in treating early gastric cancer, particularly when the margin of lesion is unclear, and depth of cancer invasion is estimated to be submucosal. Risks of lymph node metastasis in these lesions are reportedly minimal as well. Quality of life scores did not decrease when the patients were treated by lasers, but did so statistically significantly in the surgically treated group of patients. Therefore, we conclude that the endoscopic laser is the treatment of choice of treatment for early gastric cancer as a local curative procedure in the aged if they have a curable lesion as mentioned above. As a palliative treatment, 34 patients with neoplastic obstruction of the esophagus and stomach were treated by dilators with or without intubation of prosthesis tube and laser recanalization. Functional efficacy (ability to eat solid or semi-solid diet which could not be eater before treatment) was noted in 64% of 11 cases treated by dilators alone, 75% of 12 cases treated by intubation of prosthesis tube and 45% of 11 cases treated by lasers. There was a greater complication rate in the intubation group also. Patients with malignant stricture due to mediastinal lymph node metastasis were at higher risk of perforation.

Aged