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Biomedical subjects

T Tsutsui

Publications and source records attributed to T Tsutsui.

At least 289 records · Page 16Linked to original sources
PubMed1986

Temporal order of replication of genes responsible for hypoxanthine phosphoribosyl transferase and Na+/K+ ATPase in chemically transformed human fibroblasts.

The cytotoxic and mutagenic effects of a direct perturbation of DNA during various portions of the DNA synthetic period (S phase) of a chemically induced, transformed line (Hut-11A cells) derived from diploid human skin fibroblasts were examined. The cells were synchronized by a period of growth in low serum with a subsequent blockage of the cells at the G1/S boundary by hydroxyurea. This method resulted in over 90% synchrony, although approximately 20% of the cells were noncycling. Synchronized cells were treated for each of four 2-h periods during the S phase with 5-bromodeoxyuridine (BrdU) followed by irradiation with near-ultraviolet (UV). The BrdU-plus-irradiation treatment was cytotoxic and mutagenic, while treatment with BrdU alone or irradiation alone was neither cytotoxic nor mutagenic. The cytotoxicity was dependent upon the periods of S phase during which treatment was administered. The highest lethality was observed for treatment in early to middle S phase, particularly in the first 2 h of S phase, whereas scare lethality was observed in late S phase. The BrdU-plus-irradiation treatment induced ouabain- and 6-thioguanine-resistant mutants, while BrdU alone or irradiation alone was not mutagenic. Ouabain-resistant mutants were induced during early S phase by the BrdU-plus-irradiation treatment. 6-Thioguanine-resistant mutants, however, were induced during middle to late S phase. These results suggest that a certain region or regions in the DNA of Hut-11A cells, as designated by their specific temporal relationship in the S phase, may be more sensitive to the DNA perturbation by BrdU treatment plus near-UV irradiation for cell survival and that gene(s) responsible for Na+/K+ ATPase is replicated during early S phase and gene(s) for hypoxanthine phosphoribosyl transferase is replicated during middle to late S phase.

Bromodeoxyuridine↗
PubMed1986

Selective immunoglobulin M deficiency associated with disseminated molluscum contagiosum.

A 16-year-old girl with disseminated molluscum contagiosum (MC) was found to have a very low level of serum IgM, elevated levels of IgG and IgA, and a high level of IgE. She had normal numbers of peripheral blood IgM+, IgG+ and IgA+ B-lymphocytes but their terminal differentiation into plasma cells could not be induced by pokeweed mitogen (PWM) in vitro. On the other hand, the patient's T-cells showed normal helper functions in the PWM system and normal interferon (IFN) production in vitro. However, the IgM+ B-cells can be induced to differentiate into IgM secreting cells by Epstein-Barr virus (EBV), suggesting that the genetic mechanism for synthesis of the component immunoglobulin proteins is present. T-cell functions were impaired, as shown by delayed type cutaneous hypersensitivity (DTH) and mitogen response. The data suggest that the selective IgM deficiency of the patient is due mainly to defects in B-cells at the terminal differentiation stage, but immunological abnormalities are present in both B and T-cell systems. Neutrophil functions examined were normal. MC was treated by intravenous injection of IFN without any side effects; however, no clinical improvement was achieved.

Adolescent↗
PubMed1986

Effects of an expanding supratentorial mass on the auditory brain-stem responses in baboons.

This study was carried out to investigate the effects of an expanding supratentorial mass on auditory brain-stem responses (ABRs). A balloon was inserted into the supratentorial epidural space of seven baboons (in two cases, in the right occipital area; in five cases, in the right temporal area). The balloons were inflated at a rate of 0.2 ml/minute to increase intracranial pressure (ICP). ICP (right frontal epidural pressure) and blood pressure (BP) were continuously recorded. Recordings of ABRs (vertex to mastoid on both sides) were made serially. Pupillary changes were also recorded. At 30 mmHg ICP, the amplitude of wave V on the right side was observed to be significantly attenuated (p less than 0.02). At 50 mm Hg ICP, the latency of wave V on the right side was significantly prolonged compared with that at 30 mm Hg ICP (p less than 0.02). At 70 mmHg ICP, significantly decreased amplitude of wave V on the left side was also observed (p less than 0.02, from the control), associated with significant increased latency of wave IV on the right side (p less than 0.01, from the control; p less than 0.05, from 50 mm Hg ICP). Finally, waves IV and V on both sides substantially disappeared at 100 mm Hg ICP. Anisocoria appeared in four animals at 30-50 mm Hg (mean +/- SD; 45 +/- 8.7) ICP. The amplitude of wave V was significantly decreased in these circumstances (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The effects of a supratentorial mass lesion on brain-stem auditory evoked potentials and short latency somatosensory evoked potentials.

Nineteen patients with unilateral supratentorial mass lesion and without any evident clinical signs of transtentorial herniation were studied with Computed Tomography (CT), brain-stem evoked potentials (BAEPs) and central conduction time (CCT) of short latency somatosensory evoked potentials (SEPs). Sixteen had tumours, two had intracranial haematoma and one had chronic subdural haematoma. CT detected the initial signs of transtentorial herniation in every case. Preoperative I-V interpeak latency (IPL) was significantly (M + 2SD) prolonged in 26% of cases on the lesion side and in 21% of cases on the opposite side. The mean I-V IPL was significantly prolonged both on the lesion side and the opposite side (P less than 0.01, P less than 0.02, respectively). Suppression of Wave V (M-2SD) was seen only in two cases, however, the mean amplitude of Wave V was significantly decreased both on the lesion side and on the opposite side (P less than 0.001, P less than 0.01, respectively). CCT of SEPs was significantly (M + 2SD) prolonged in 33% of cases on the lesion side and in only 13% on the opposite side. The mean CCT was, however, significantly prolonged both on the lesion and on the opposite side (P less than 0.001, P less than 0.02, respectively). Postoperative I-V IPL was significantly prolonged in only 11% of cases while the mean I-V IPL was still significantly prolonged (P less than 0.01) and the mean amplitude of Wave V was still suppressed (P less than 0.001) on the lesion side.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Vincristine sulfate-induced cell transformation, mitotic inhibition and aneuploidy in cultured Syrian hamster embryo cells.

Vincristine, a naturally occurring Vinca alkaloid and widely used anti-neoplastic agent, was examined for its ability to induce cell transformation, inhibition of growth and mitosis, and genetic effects in Syrian hamster embryo cells in culture. Treatment of the cells with doses of less than or equal to 1 ng/ml vincristine sulfate (VCR) had no effect on cell growth, while exposure to greater than or equal to 3 ng/ml reduced the growth rate and treatment with 30 ng/ml resulted in no detectable increase in cell number. At this latter dose the mitotic index of the cells increased significantly suggesting that VCR delayed completion of mitosis. Exposure of the cells to VCR at doses of 1-10 ng/ml for 48 h resulted in morphological transformation of the cells in a doserelated fashion. The vincristine-treated transformed colonies were morphologically indistinguishable from colonies transformed by benzo[a]pyrene or other chemical carcinogens. Morphological transformation was induced by VCR at non-toxic and slightly toxic doses as measured by a reduction in colony-forming ability of the treated cells. Over the dose range which resulted in cell transformation, VCR failed to induce either detectable gene mutations at two genetic loci, unscheduled DNA synthesis, or chromosome aberrations in the Syrian hamster embryo cells. However, a significant dose-dependent increase in aneuploid cells with a near-diploid chromosome number was induced by VCR. Both chromosome losses and gains were induced which is consistent with a non-disjunctional mechanism. These results further support our hypothesis that aneuploidy is one possible mechanism for induction of this early step in the neoplastic transformation of Syrian hamster embryo cells. Furthermore, these findings indicate that VCR may have some carcinogenic potential if exposure to rapidly dividing cells occurs.

Aneuploidy↗
PubMed1986

Alteration in diethylstilbestrol-induced mutagenicity and cell transformation by exogenous metabolic activation.

It was shown previously that diethylstilbestrol (DES) can induce morphological and neoplastic transformation of Syrian hamster embryo cells in culture in the absence of detectable gene mutations or DNA damage. However, in the presence of exogenous metabolic activation with rat liver post-mitochondrial supernatant, DES can induce unscheduled DNA synthesis. In this report we have examined whether with exogenous metabolic activation DES can also induce biological effects possibly related to its carcinogenicity, i.e. specific locus mutations in Syrian hamster embryo cells and cell transformation. We observed that DES was mutagenic only in the presence of exogenous metabolic activation. DES induced morphological transformation both in the absence and presence of exogenous metabolic activation. Enhanced cell transformation was observed in the presence of exogenous metabolic activation. These results indicate that two pathways may exist for the induction of cell transformation by DES. One does not apparently involve direct DNA damage, and the other, which requires rat liver post-mitochondrial supernatant-mediated exogenous metabolic activation, is associated with DNA damage and mutagenicity. These results may provide an experimental model to elucidate the biological properties of DES metabolites.

Animals↗
PubMed1986

Arterial pressure pulsation during nonpulsatile biventricular bypass experiments: possible idioperipheral pulsation.

During nonpulsatile biventricular bypass (NPBVB) experiments, regular fluctuations of arterial pressure were observed in all five long-term animals whose ventricles were fibrillated. Analysis of the characteristics of this fluctuation was performed retrospectively. The pulse pressure of this fluctuation increased gradually after the first 2 weeks. They were 6.7, 7.6, 10.2, and 12.4 mm Hg on the fortieth, sixtieth, eightieth, and ninetieth postoperative day, respectively, in the animal surviving for 99 days. Cycle rate was generally high for the first 40 days, and then decreased to approximately 40 cycles/min in calves alive for greater than 90 days. The beat rate of these arterial pressure fluctuations was lower than atrial but similar to respiratory cycle rates. However, no flow fluctuations were observed in conjunction with the arterial pressure oscillations. Therefore, neither atrial contractions nor the mechanical effects of respiration were causing the pressure pulsations. Though further investigations are necessary, it is highly suggestive that this phenomenon was derived from the vasomotor center and can be called "idioperipheral pulsation." It is conceivable that the NPBVB animals adapted to the nonpulsatile condition by adding active pulsatile components of their own to maintain adequate peripheral circulation.

Animals↗
PubMed1986

Comparison of fast flow and initial slope index values for cerebral blood flow following subarachnoid haemorrhage.

Forty five patients with subarachnoid haemorrhage proved by lumbar puncture underwent serial measurements of cerebral blood flow and central conduction time. When the initial slope index (ISI) value for cerebral blood flow is considered there is a clear relationship between reduction of cerebral blood flow and deteriorating clinical grade. This relationship is not so clearly demonstrated using the fast flow (f1) value for cerebral blood flow. When cerebral blood flow is compared to central conduction time those patients with a central conduction time longer than 6 X 4 ms have a significantly lower CBFisi but not a significant lower CBFf1. Furthermore, using the ISI value, there is a linear relationship between the fall in cerebral blood flow and the lengthening of CCT below a threshold blood flow of about 35 ml/100 g/min. This relationship is not demonstrated with the CBFf1 value. It therefore appears that the ISI value for cerebral blood flow shows a greater correlation between clinical and electrophysiological events than the f1 value.

Adolescent↗
PubMed1986

[Clinical study of protein and amino acids metabolism in surgical infection--significance of administration of branched chain amino acids].

Anastomotic leakage and fistula of alimentary tract are accompanied by peritonitis because of exudation of contents in the digestive canal. In order to inquire about metabolism of protein and amino acids in surgical infection, this study was performed by the method of a time related cross-over trial, comparing high branched chain amino acids (BCAA) solution with low BCAA solution. The following results were obtained. When metabolism is physiologically compensated in infection, it was suggested that there appeared to be gluconeogenesis, ureagenesis and a liver disturbance accompanied in the early phase of sepsis. Administration of BCAA leads to an inhibition of muscle protein break down and a promotion of visceral protein synthesis in the case of severe infection. Administration of BCAA enriched amino acids solution have an important therapeutic measure under severe stressed condition and a significant role in medicine.

Adult↗
PubMed1986

Requirement of long progression time for the expression of neoplastic phenotypes following direct perturbation to specific region(s) of DNA of Syrian hamster embryo cells.

We have studied the neoplastic transformation of early passage Syrian hamster embryo cells in culture, which were initiated by a specific perturbation of DNA replicated during different periods of S phase. The cells were treated with a "1-h pulse" of 5-bromodeoxyuridine (BrdUrd), followed by a "5-min" irradiation with near ultraviolet (near UV) light. The treated cells were successively subcultured and tested for growth in soft agar and tumorigenicity in newborn hamsters. Neoplastic transformation was induced by treatment with BrdUrd followed by near UV irradiation within the first 4 h of S phase, which was 5 h in duration. Cells treated with BrdUrd plus near UV irradiation during late S phase (the last hour) or during the absence of DNA synthesis (outside of the S phase) were not transformed. In addition, cultures treated in either G1, G2, or S phase with BrdUrd alone or with near UV alone also were not transformed. While morphological transformation, somatic mutation, and DNA and chromosomal aberrations can be observed either immediately or after a few cell divisions, 100 to 200 population doublings after the treatment were required for the emergence of a neoplastic subpopulation, as measured by anchorage independent growth and tumorigenicity. Furthermore, cellular DNA replicated during the first 4 h of S phase is sensitive to the perturbation which leads to neoplastic transformation. These results indicate that the direct perturbation of specific region(s) of cellular DNA can initiate the neoplastic transformation process; but for full expression of the neoplastic phenotypes, a long progression time is required for the acquisition of anchorage-independent growth and tumorigenicity.

Animals↗