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Biomedical subjects

S Maeda

Publications and source records attributed to S Maeda.

At least 757 records · Page 42Linked to original sources

Expression of tissue-specific genes in transgenic mice.

The ability to introduce cloned genes into mouse germ line has been used for analyzing cis-acting DNA sequences involved in tissue-specific and developmental regulation of the introduced gene. Using this system we have attempted to produce a transgenic mouse model for human dominantly inherited disease, familial amyloidotic polyneuropathy. Recently the mutant transthyretin gene which is considered to be responsible for this disease has been cloned and well characterized at molecular level. We have produced transgenic mice by microinjecting human mutant gene. Amyloid deposition was observed in the mucosa of alimentary tract and renal glomeruli, suggesting that this approach is successful in establishing the mouse model for human genetic disease. In addition, these experiments suggest that the expression of the mutant gene is regulated normally during developmental process and that the cause of adult onset is not due to the dysregulation of this gene expression.

Amyloidosis↗

Heterogeneous origin of established non-T,non-B cell lines from two adolescent patients with acute lymphoblastic leukemia.

Three leukemic cell lines were established from the bone marrow cells of two adolescents with non-T,non-B acute lymphoblastic leukemia (ALL) at relapse. Two cell lines from a 14-year-old girl and one from an 11-year-old boy were designated as KH-3A, KH-3B and KH-4, respectively. Leukemic cells started to grow attached to the bone marrow stromal (BMS) cells. KH-3A was positive for OKIa1 and positive at low percentages for B1, Leu-1 and J5 antigens; KH-3B reacted with OKIa1 and J5. Except for OKIa1, these two cell lines showed no surface marker change after 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment. On TPA treatment, clones (KH-3A-2 and KH-3A-3) isolated from KH-3A in agarose showed the induction of differentiation into T and B cell lineage. KH-4 was positive for OKIa1 and positive at low percentages for B1 and J5, and showed a strong reaction with OKIa1, B1 and J5 after TPA treatment. T cell receptor (TCR) beta-chain gene and immunoglobulin gene (JH and C mu) rearrangements were found in KH-3A, KH-3B, and sublines isolated from KH-3 (KH-3A-2 and -3) simultaneously. These findings indicate that BMS cells are useful for the establishment of leukemic cell lines and that some common ALL (cALL) cell populations may be heterogeneous.

Adolescent↗

Primary choriocarcinoma of the urinary bladder.

We report a case of choriocarcinoma of the bladder. The initial biopsy of the bladder tumor showed co-existence of choriocarcinoma and transitional cell carcinoma, while the cystectomized bladder tumor and metastatic tumors were composed only of choriocarcinoma. The diagnosis of choriocarcinoma was confirmed morphologically and by the demonstration of hCG in the tumor and in the serum.

Carcinoma, Transitional Cell↗

Familial atrial standstill caused by amyloidosis.

Three of nine siblings were affected by atrial standstill. Clinical, electrophysiological, and histological findings in two of these cases were studied. Electrophysiological studies showed persistent atrial standstill in one and partial atrial standstill in the other. Biopsy specimens of the right atria showed amyloid deposits, but specimens of the right ventricles and skin did not. Neither patient had peripheral neuropathy, gastrointestinal disorder, or renal dysfunction. Familial atrial standstill is usually associated with peripheral neuropathy. In the two cases studied amyloid deposition mainly affected the atrium, rather than the ventricles or other organs, and caused atrial standstill.

Adult↗

Occurrence of methionine-enkephalin-like immunoreactive cells in the feline vagus nerve.

The occurrence of peptidergic cellular elements in the feline vagus nerve was examined by an immunohistochemical method. Some methionine-enkephalin-like immunoreactive cells were present around a few capillaries within the vagus nerve, whereas substance-P- and vasoactive-intestinal-polypeptide-like immunoreactive cells were not observed. The methionine-enkephalin-like immunoreactive cells had an oval shape and their diameter was 7-10 micron. These cells appeared to be in contact with the pericyte of the capillaries. Though the physiological function of these enkephalin-positive cells is unclear, our findings suggest that they can act as endocrine cells and release methionine-enkephalin into the capillaries.

Animals↗

[Testing performance of the improved pinhole collimator and its application to small animals].

Testing performance of the improved pinhole collimator of 1.5 mm aperture attached to the gamma camera was carried out with three kinds of radionuclides, 99mTc, 67Ga and 131I, using a hand-made phantom. The results obtained in this experiment were compared to those obtained with a human pinhole collimator of 4 mm aperture. Those were nearly understood by taking account of the effective aperture of a pinhole collimator for each effective photon energy. And all scintigrams obtained from rats with various scintigraphy showed high resolution images.

Animals↗

Paraneoplastic cortical cerebellar degeneration. A neuropathological study of an autopsy case in comparison with cortical cerebellar degeneration in alcoholics.

A case is described of paraneoplastic cortical cerebellar degeneration in a patient with a small cell carcinoma of the lung. Following therapy, clinical improvement of cerebellar ataxia had been observed. The most severe degeneration was found in the superior aspects of the vermis and in the anterior and simple lobes as well as in the inferior aspects of the hemisphere. In addition to this distribution of degenerative lesions, uneven loss of Purkinje cells was apparent. Such distribution patterns in this case were apparently compatible with those of alcoholic cortical cerebellar degeneration (ACD), although the lesions were less severe than in ACD. Furthermore, dendritic changes in the Purkinje cells including loss of the spiny branchlets, focal swelling of the dendrites, and disappearance of secondary and tertiary branches were remarkable. It is noteworthy that these cells showed various stages of degeneration before cell loss occurred. These data suggest that the degree of vulnerability varies among Purkinje cells, and that this could be related to the uneven loss of these cells. It is proposed that, although this case and cases of ACD have both similarities and differences in their neuropathological aspects, it is apparent that both conditions have some common morphopathogenetic factor.

Alcoholism↗

[A glomus tumor of the stomach associated with a lipoma].

A case of Glomus tumor of the stomach associated with a lipoma in a 65-year-old female is reported. The patient complained of epigastralgia for three months prior to her admission. X-rays, as well as gastroscopic examinations, revealed two submucosal tumors, one located along the greater curvature of the gastric antrum and the other on the posterior wall of the upper corpus. A preoperative angiographic study showed hypervascularity and tumor staining. Histologically, one tumor was diagnosed as being Glomus tumor and the other, a lipoma. Thus this rare case of two submucosal tumors in the stomach is discussed and 39 previous gastric Glomus tumor cases found in the domestic literature are reviewed.

Aged↗

[A case of renal cell carcinoma suspected of multilocular cystic nephroma].

A 52-year-old, healthy looking woman was referred for further evaluation of left renal mass, She had had a history of hematuria for ten years. Admission laboratory studies were within normal limits except for slight elevation of white blood cell count, c-reactive protein, blood sedimentation rate and immunosuppressive acidic protein. Retrograde pyelography demonstrated a large mass with ringed calcification in the middle lobe of the left kidney. The multiloculated mass was also confirmed by computed tomography and ultrasonography. Selective left renal arteriography showed stretched arteries and irregularity and tortuosity of the smaller vessels. Under a presumptive diagnosis of multilocular cystic nephroma or renal cell carcinoma, left radical nephrectomy was performed. In surgical specimen, many lobules were filled with serous fluid and clotted blood. Microscopic examination revealed that the lining of the cyst wall consisted of renal cell carcinoma cell. At present, 5 months after the operation, she is well without any signs or symptoms of recurrence.

Carcinoma, Renal Cell↗

Gene rearrangements of T cell receptor beta and gamma chains in HTLV-I infected primary neoplastic T cells.

Rearrangements of T cell receptor beta and gamma chain (T beta and T gamma) genes were analyzed by Southern blot method in samples from 30 patients with adult T cell leukemia (ATL) and 17 patients with non-ATL T cell neoplasms. The DNA probes used were the constant and joining region of T beta gene and the joining region of T gamma gene. Rearranged bands of T beta gene on one or both allelic chromosomes were detected in all neoplastic T cells, even those of smoldering ATL, in which only a small percentage of peripheral blood T cells were detected as leukemic. T gamma gene was rearranged in the cells of all but one patient, the exception being one ATL patient. In order to test whether any given variable region (V) of T beta gene was expressed in ATL cells, two functionally rearranged V beta sequences of ATL were compared with a V beta sequence from T cells acute lymphoblastic leukemia cells. No significant homologies were noted among the three deduced gene product amino acid sequences, confirming that T beta molecules of ATL cells contained no specific structures in common. The observed heterogeneity of T beta and T gamma gene rearrangements in ATL cells further supported these findings.

Amino Acid Sequence↗

hst-1 transforming protein: expression in silkworm cells and characterization as a novel heparin-binding growth factor.

A protein encoded by an hst-1 transforming gene was expressed in silkworm-derived BmN cells and secreted into the culture medium using a recombinant baculovirus vector. The strong affinity for heparin of the secreted protein made it possible to purify the hst-1 protein to homogeneity in a two-step procedure. The purified hst-1 protein has a molecular weight of 18,000 and stimulates both DNA synthesis in NIH3T3 cells and human umbilical vein endothelial cell proliferation. In addition, morphological changes and anchorage-independent growth of NIH3T3 cells are induced by this product. These results show that the hst-1 transforming protein is a novel heparin-binding growth factor as predicted by nucleotide sequence analysis.

Animals↗

Evidence for phosphorylation of trans-activator p40x of human T-cell leukemia virus type I produced in insect cells with a baculovirus expression vector.

Human T-cell leukemia virus type I (HTLV-I) encodes a trans-activator protein p40x which positively regulates transcription of the viral RNA as well as interleukin-2 and its receptor genes. We placed a cDNA coding for p40x in baculovirus Bombyx mori nuclear polyhedrosis virus (BmNPV) expression vectors. Infection of BmN cells derived from an insect, B. mori (silkworm), with a recombinant virus led to the production of soluble p40x. The biological activity of the recombinant p40x was demonstrated by introducing the protein into intact NIH 3T3 cells that had been selected for genomic integration of HTLV-I LTR connected with the CAT gene. Immunocytochemical and cell fractionation analyses showed the localization of p40x in both the cytoplasmic and nuclear fractions of BmN cells. Analyses of 32P-labeled proteins of BmN cells by cell fractionation and subsequent immunoprecipitation revealed that the p40x present in each subcellular fraction was phosphorylated. The post-translational modification was inhibited by the addition of a protein kinase inhibitor K252a during the metabolic labeling of BmN cells. Phosphoamino acid analysis indicated that the phosphorylation occurred on serine residues of p40x.

Animals↗

C-myc expression in lymphocytes of MRL/MP-lpr mice activated by A23187 and TPA.

In order to analyse the molecular mechanism of lymphocyte activation defect in MRL/MP-lpr (MRL/1) mice, c-myc proto-oncogene expression was examined in MRL/1 lymph node cells stimulated by various agents. Since a transient increase of c-myc RNA in early hours is required for lymphocyte activation, detection of c-myc messenger RNA is useful to determine whether or not an appropriate signal is transduced to the nucleus. Stimulation by concanavalin A (Con A) plus 12-O-tetradecanoyl phorbol 13-acetate (TPA) or A23187 plus TPA markedly increased c-myc mRNA expression and cell proliferation, whereas stimulation by Con A alone failed to do so. These results suggest that an abnormality exists in the early signal transduction process, and that it could be bypassed by calcium influx and direct activation of protein kinase C.

Animals↗

[Chromosome abnormalities in early cancers].

The chromosome changes in early cancer had been thought to be difficult to analyse because of the technical reasons and of the complex nature of the chromosomal abnormalities as compared with hematological diseases having simple diploid karyotype. Recent advances allowed to analyse the chromosomes of solid tumors by the improved technics for cell disaggregation, short term culture, and chromosome banding. Although some advanced solid cancers kept the simple near by diploid chromosomal features, many tumors such as cervical cancers reveal complex chromosomal changes already in the pre-invasive stage. Much more data must be collected to evaluate the role of chromosomal changes in benign and early malignant tumors.

Chromosome Aberrations↗

Stimulation of phospholipase A2 and vascular permeability by an extract of granuloma induced in the rat by carrageenin.

Isolation from carrageenin-induced granuloma of rat of factors affecting phospholipase A2 (PLase A2) activity was attempted. Excised granuloma was extracted with 2% phenol and denatured both at acidic and alkaline pH's in boiling water. The extract was adsorbed on charcoal and eluted in an alkaline milieu. Following gel chromatography of the eluate on Sephadex G-25, the effect of this fraction on PLase A2 prepared from rabbit peritoneal exudates was examined. Materials affecting PLase A2 activity were eluted slightly behind the peak of saccharides having an approximate molecular weight of 800. Activation of PLase A2 was most pronouncedly observed in the sample prepared from 5 days granuloma. Activating effect on PLase A2 was not observed with the sample prepared from control rat skin. The effect of fractions that contained PLase A2 activating components on vascular permeability was investigated by measuring the leakage of i.v. administered pontamine blue. Injection of the sample containing PLase A2-activating materials into mouse paw induced the increase of vascular permeability in a dose dependent manner. Maximal effect was observed also in the sample obtained 5 days after the injection of carrageenin. Thus, the activating components may be involved in the processes of inflammation.

Animals↗