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Biomedical subjects

K Tsuboi

Publications and source records attributed to K Tsuboi.

At least 91 records · Page 5Linked to original sources

[Low incidence of point mutation of N-ras oncogene in human gliomas].

We examined the incidence of point mutations in codon 12 and 61 of N-ras gene in human gliomas using PCR with mismatched primers. This method detects point mutations. PCR with mismatched primers induced restriction sites in normal DNA but not in mutational DNA. Genomic DNAs were extracted from paraffin-embedded tissues and were amplified with nested PCR. Among 17 cases, point mutation has not been able to be found so far, when examined in codon 12 of N-ras gene and among 10 cases in codon 61 of N-ras gene. It can thus be said that point mutational activation of N-ras oncogene is an uncommon event in human gliomas.

Base Sequence↗

Nuclear characterization and G2M ploidy in human brain tumors using semiautomated image analysis.

We used image analysis to study nuclear morphometry and DNA content in relation to time to tumor progression in a series of 88 patients with brain tumors. Clinical follow-up was obtained for 73 patients. The patients with diploid tumors had a longer time to tumor progression than those with triploid, tetraploid, or hypertetraploid tumors. Mean SG2M-DNA indices (DIs) increased significantly with a increase in mean DIs in all tumors. The mean DIs appeared to be dependent on the number of SG2M phase cells. We conclude that tumors with hypertetraploid in G2M ploidy are highly malignant. Those tumor cells have a large nuclear size, much deformity in nuclear shape, and great proliferative potential. The G2M-tetraploid tumors showed a shorter time to tumor progression when the number of SG2M fractions was large. In contrast, the G2M-hypotetraploid tumors showed a longer time to tumor progression in comparison with other tetraploid and hypertetraploid tumors, but the difference was not significant.

Aneuploidy↗

Charged-particle mutagenesis II. Mutagenic effects of high energy charged particles in normal human fibroblasts.

The biological effects of high LET charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 micrometer2 and 0.09 to 5.56 x 10(-3) micrometer2, respectively. The maximum values were obtained by 56Fe with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(-5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.

Cell Death↗

Basal ganglia germinoma with crossed cerebellar diaschisis--case report.

An 8-year-old boy presented with a germinoma of the right basal ganglia manifesting as gradual onset of mild left hemiparesis. Computed tomography (CT) and magnetic resonance imaging disclosed a mass lesion in the right basal ganglia with mild right cerebral hemiatrophy. Single photon emission CT revealed decreased cerebral blood flow in both the right cerebral and left cerebellar hemispheres, or crossed cerebellar diaschisis. The histology of a specimen from a stereotactic needle biopsy was compatible with two-cell pattern germinoma. After irradiation and chemotherapy, the mass lesion disappeared completely. The clinical symptoms and crossed cerebellar diaschisis gradually improved.

Basal Ganglia Diseases↗

[Leiomyosarcoma of ileocecal mesentery--a case report].

We report a case of leiomyosarcoma whose origin was near the root of ileocecal mesentery and extended into the retroperitoneum. Preoperative imaging examination, including CT, MRI and angiography clearly displayed its origin and retroperitoneal extension. These results contributed to treatment planning.

Cecum↗

[Clinical relevance of abdominal imaging examinations in malignant lymphoma].

We prospectively evaluated the clinical importance of abdominal imaging examinations (US, CT, upper gastrointestinal barium X-ray) in 233 consecutive patients who gave informed consent for the examinations. The examinations revealed intra-abdominal lesions in 99 of 233 patients. Intra-abdominal lymph nodes were most frequently affected, followed by stomach, spleen, liver, small intestine and large intestine. In Hodgkin's lymphoma, no gastrointestinal involvement was noted but one in the small intestine. Prognosis was poorer with advancing stage according to Ann Arbor classification. However, the presence or absence of intra-abdominal lesions did not influence the prognosis when patients were matched for the stage. Abdominal imaging examinations altered the bed-side staging to more advanced stages in 22 of 163 patients with stage I through stage III lymphoma, influencing prognosis as well as the decision of therapeutic modalities. These three diagnostic modalities were complementary to one another. In conclusion, every one of these abdominal imaging examinations is important for planning the management of patients with malignant lymphoma.

Abdomen↗

Commitment reversion model of unrestricted cell growth.

Through the analysis of accumulated experimental data of cell growth, a model of unrestricted cell growth is presented here. This model is based hypothetically on the cellular commitment to senescence as in the previously presented commitment theory. Cells are divided into 3 types, namely uncommitted cells, committed cells and terminal cells. The division of an uncommitted cell produces an uncommitted cell itself and a committed cell of the first generation. This committed cell goes through a limited number of cell divisions until the cells become non-dividing terminal cells. It is hypothesized that during a committed cell division, there is a very small probability that an uncommitted cell may be generated. With computer simulations, it is estimated that a committed cell of the first generation may divide around 30 times until they become non-dividing terminal cells, and that the probability of an uncommitted cell regeneration for each committed cell division may be 2(-H). This hypothesis may possibly clarify some aspects of the biological phenomena of cell growth, which can not be explained by the previous commitment theory, such as the growth pattern of cultured diploid cells, cancer initiation and promotion, and cancer progression and metastasis.

Animals↗

Giant aneurysm at the junction of the left internal carotid and persistent primitive trigeminal arteries--case report.

A 67-year-old female presented with an unruptured giant aneurysm at the junction of the left internal carotid artery (ICA) and the persistent primitive trigeminal artery (PTA), manifesting as progressive left abducens nerve paresis. The PTA was clipped by the left suboccipital approach. The aneurysm was then successfully thrombosed by ligation of the left ICA at the cervical portion following left superficial temporal artery-middle cerebral artery anastomosis. The left abducens nerve paresis improved postoperatively. Magnetic resonance imaging was of considerable value in the pre- and postoperative evaluation of the giant aneurysm.

Abducens Nerve↗

Charged-particle mutagenesis. 1. Cytotoxic and mutagenic effects of high-LET charged iron particles on human skin fibroblasts.

Cytotoxic and mutagenic effects of high-LET charged iron (56Fe) particles were measured quantitatively using primary cultures of human skin fibroblasts. Argon and lanthanum particles and gamma rays were used in comparative studies. The span of LETs selected was from 150 keV/microns (330 MeV/u) to 920 keV/microns (600 MeV/u). Mutations were scored at the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus using 6-thio-guanine (6-TG) for selection. Exposure to these high-LET charged particles resulted in exponential survival curves. Mutation induction, however, was fitted by the linear model. The relative biological effectiveness (RBE) for cell killing ranged from 3.7 to 1.3, while that for mutation induction ranged from 5.7 to 0.5. Both the RBE for cell killing and the RBE for mutagenesis decreased with increasing LET over the range of 1.50 to 920 keV/microns. The inactivation cross section (sigma i) and the action cross section for mutation induction (sigma m) ranged from 32.9 to 92.0 microns2 and 1.45 to 5.56 X 10(-3) microns2; the maximum values were obtained by 56Fe with an LET of 200 keV/microns. The mutagenicity (sigma m/sigma i) ranged from 2.05 to 7.99 X 10(-5) with an inverse relationship to LET.

Cell Survival↗

Blocking type immunoglobulins in patients with nongoitrous primary hypothyroidism in area of iodine deficiency.

We have evaluated the role of circulating serum immunoglobulins (IgG) which inhibit the growth of thyroid in the etiology of thyroid atrophy in endemic cretinism. Twenty nongoitrous cretins (13 women and 7 men, age range: 9-33) were classified on the basis of clinical criteria for cretinism in China. They were born and living in an iodine deficient area, Xinjiang, northwest China. Antimicrosomal antibody titers were negative in all serum. Nine patients (seven women and two men; age range: 11-23) were biologically primary hypothyroid. Seven subjects were of a myxedematous form and two subjects were of a mixed form. We have studied thyroid-growth inhibiting immunoglobulin (TGII) activity that was measured as an inhibitory effect of 4 mg/ml IgG on TSH-induced [3H]-thymidine incorporation into the DNA of a rat thyroid follicular cell line, FRTL5 cells. Six (five women and one man) out of the nine patients with primary hypothyroidism (66.7 percent) had TGII. We also measured other growth-blocking IgG that inhibited [3H]-thymidine incorporation into DNA stimulated by insulin-like growth factor-I (IGF-I), a growth factor working through a cAMP-independent pathway. Five (three women and two men) out of nine patients (55.6 percent) with nongoitrous primary hypothyroidism had IGF-I-blocking IgG. These results indicate that TGII plays an important role in atrophy of the thyroid in spite of increased serum TSH concentrations, and IgG which inhibits thyroid growth stimulated by IGF-I also might play a role in thyroid atrophy in some endemic cretins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Amplification of L-myc oncogene in malignant meningioma. Case report].

Amplification of L-myc oncogene was noticed in a malignant meningioma originating from the right sphenoidal wing of a 54-year-old female. The patient underwent three surgical resections plus radiotherapy over a period of 11 years and then the growth rate of the tumor became much greater with a severely invasive appearance. Using Southern blot hybridization, L-myc amplification was examined on the specimen resected at the fourth operation. As a result, approximately five-fold amplification was confirmed, which has not been previously reported except for that in a small cell carcinoma of the lung. This result may suggest that L-myc amplification is responsible to some extent for the malignant transformation in this meningioma.

Female↗

Isolated cerebral varix with magnetic resonance imaging findings--case report.

A rare case of isolated cerebral varix of the left deep sylvian vein was discovered incidentally in an 11-year-old boy by computed tomographic scanning, magnetic resonance (MR) imaging, and cerebral angiography. MR imaging was most useful in diagnosis of cerebral varix. Review of 21 similar reported cases shows no significant in age, sex, location, or size character.

Brain↗

Thyroid atrophy in myxedematous endemic cretinism: possible role for growth-blocking immunoglobulins.

We have examined the ability of IgGs obtained from 8 endemic cretins to inhibit TSH-stimulated thyroid cell growth in culture. Clinical and laboratory evidence for hypothyroidism was present in six subjects; the two remaining patients had borderline low serum T4, normal T3 and exaggerated TSH response to TRH. In six patients 2 mg IgG exhibited an inhibitory effect in the cellular growth expressed by a diminished incorporation of 3H-thymidine into the DNA of TSH-stimulated FRTL-5 cells (range: 26-87% inhibition). Seven patients presented clinically with thyroid atrophy of relatively small thyroid enlargements for the degree of chronic iodine deficiency that was present in the area. The remaining subject had a large multinodular goiter and IgG purified from this patient had no inhibitory effect in the FRTL-5 cellular growth. A direct relationship was noted between the degree of thyroid growth inhibition (%) and the basal serum TSH concentration. We conclude that the presence of thyroid growth inhibiting immunoglobulin may be related to the absence of thyroid growth or even thyroid atrophy in endemic cretins.

Adolescent↗

Initiation of wound healing by proteinases released from damaged cells.

The wound-healing process is initiated as soon as the tissue is injured. Herein, we demonstrate that c-fos and c-myc mRNA transcripts are promptly increased in the wounded tissue in vivo and in vitro. A buffer solution from scraped serum-starved quiescent fibroblasts, when added to resting fibroblasts, caused an increase of c-fos and c-myc mRNA among the indicator cells. Soluble factors contained in the wounding supernatant are responsible for these phenomena, and we call them wounding factors. Addition of proteinase inhibitors to the culture medium drastically reduced the c-fos mRNA induction by the wounding factors. Exogenously added trypsin or thrombin mimicked the activity of wounding factors. These results suggest that wounding causes soluble factors including various proteinases to be released from the damaged cells, which trigger the adjacent cells to respond to the injury.

Animals↗

Soluble factors including proteinases released from damaged cells may trigger the wound healing process.

The wound healing process is initiated as soon as tissue is injured. Herein, we demonstrate that c-fos and c-myc mRNA transcripts are promptly increased in the wounded tissue in vivo and in vitro. A buffer solution from scraped serum-starved quiescent fibroblasts, when added to resting fibroblasts, caused the increase of c-fos and c-myc mRNA among the indicator cells. Soluble factors contained in the wounding supernatant are responsible for these phenomena and we call them wounding factors. Addition of proteinase inhibitors to the culture medium drastically reduced the c-fos mRNA induction by the wounding factors. Exogenously added trypsin or thrombin mimicked the activity of wounding factors. These results suggest that wounding causes soluble factors including various proteinases to be released from the damaged cells, which trigger the adjacent cells to respond to the injury.

Animals↗