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Biomedical subjects

J Kato

Publications and source records attributed to J Kato.

At least 379 records · Page 21Linked to original sources

[Clinical studies of renal pelvic and ureteral tumors: an analysis of 611 registered cases and progress of treatment].

A review of 611 cases of renal pelvic or ureter tumor registered in Tokai Urological Tumor Registry for the past 10 years from 1980 and comparison of results between the first and latter half was made. The number of renal pelvis tumor was 347 and that of ureter tumors was 264. Clinical stages and pathological grades of the tumor were as follows; Ta, 11.9; T1, 31.8; T2, 14.4; T3, 24.3; T4, 17.6% and G1, 10.5; G2, 49.3; G3, 33.0%. Higher stages and grades were observed in the recent 5 years. Of 409 cases (66.9% in total cases) treated by total nephroureterectomy, 28.3% of the first and 49.0% of the latter half were treated adjunctively by chemotherapy. Five years relative survival rates of these two groups were 49.4 and 47.3%, respectively, suggesting no improved results. A new treatment strategy such as neoadjuvant chemotherapy or lymphadenectomy is expected to improve the prognosis.

Adult↗

Platelet-derived growth factor indirectly stimulates angiogenesis in vitro.

We evaluated the effect of platelet-derived growth factor (PDGF) on capillary formation using an in vitro angiogenesis model system in which microvascular fragments and myofibroblasts (Mfs) isolated from rat epididymal lipid tissues were grown in co-culture. In this system Mfs induce capillary formation by producing an endothelial cell growth factor and by secreting extracellular matrix components that cause endothelial cells to form cordlike structures. Addition of PDGF enhances in vitro capillary growth. Although some recently described microvascular endothelial cells display PDGF receptors and respond to PDGF, we found no evidence for direct PDGF action on the rat epididymal microvascular endothelial cells. Rather, we found that PDGF increased the proliferation of Mfs, as well as the production of Mf-derived endothelial cell growth factor and matrix collagen type I. Our results suggest that even in cases where the microvasculature lacks PDGF receptors, PDGF may accelerate capillary formation by activating connective tissue cells in the vicinity of endothelial cells.

Animals↗

[Usefulness of Vmax and time constant in the evaluation of left ventricular function immediately after cardiac operation].

It is difficult to evaluate the cardiac function accurately, immediately after cardiac operation, because of the restriction of measurements and the variations of loading. To evaluate the exact cardiac function during and after cardiac surgery, we examined the usefulness of unloaded maximal shortening velocity of contractile element (Vmax) and time constant of isovolumic pressure fall (TC) in the condition of hasty changing of preload and afterload. In our experiment, we used canines as our subject. Following the sedation of the canines, the left ventricular pressure (LVP) curve was recorded by using the catheter-tip manometer which was introduced into the apex of the heart. The LVP was measured in the following instances: 1) at control condition, 2) 5 minutes after the administration of dobutamine of 2 or 5 micrograms/kg/min, 3) 5, 10, 15, and 30 minutes interval after the ligation of the left anterior descending artery (LAD). In every situations, preload and afterload were changed by the temporary occlusion of the inferior vena cava or descending thoracic aorta. Vmax and TC were analyzed easily only from the LVP by the personal computer. We used Grunkemeier's method to calculate Vmax which was analyzed only from the LVP curve. We presumed that the mean value of Vmax analyzed by Grunkemeier's method was almost the same as the data by Mason's method by calculating the mean value from the given number of heart beats. Because the correlation of two methods was linear, and furthermore the slope of this regression line was 0.97 and the Y-intercept was 0.19. Vmax was the index that was comparatively independent from the loading condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Administration and dosage of iohexol, a nonionic contrast medium, for dynamic renal computed tomography.

We investigated the optimal method of administering iohexol, which contains 300 mg iodine/ml (Omnipaque 300), a nonionic contrast medium, to maintain adequate renal contrast while reducing artifacts during dynamic CT scanning. In this study, 76 patients with renal disease received 10-50 ml of iohexol as follows: group I (14 patients), 20 ml injected as an intravenous bolus for 5 sec, followed by 30 ml intravenous drip infusion for 5 min; group II (18 patients), bolus of 20 ml injected for 5 sec; group III (13 patients), 20 ml diluted with sterile water (total volume 40 ml), and injected as a bolus for 8 sec; group IV (15 patients), 20 ml injection for 5 sec followed by intravenous drip infusion of 200 ml of Hartmann-Ringer's solution given at maximum speed; and group V (14 patients), 10 ml diluted with sterile water (total volume 20 ml) injected as a bolus for 5 sec. We found that corticomedullary differentiation was most distinct on the images obtained from group IV. We concluded that a lower concentration of iohexol (150 mg iodine/ml) given by intravenous fluid loading can provide superior CT images.

Adult↗

[Computerized recording system during cardiopulmonary bypass utilizing the "GEM 6 PLUS analyzer"].

We developed a new computerized recording system to reduce artificial errors by perfusionists during cardiopulmonary bypass. This system included the efficient functions to record the progress of perfusion flow, perfusion pressure, urine output and temperatures from several sources. Furthermore, it could automatically record considerable data of the "GEM 6 PLUS analyzer" which was developed for monitoring of pH, PCO2, PO2, BE, Ca2+, K+ and hematocrit during cardiopulmonary bypass. We considered it very important that the errors of hematocrits associated with electrolytic concentrations. Therefore, we corrected the hematocrit according to a formula based on our experiments, i.e., HCT = GEMHCT + 0.28 x ([Na+]+[K+]) -44. And also we expect that the "GEM 6 PLUS analyzer" will be improved to measure Na+ value in near future.

Body Temperature↗

Changes in bone formation during experimental tooth movement after denervation of the rabbit inferior alveolar nerve.

The effects of nerve fibers on bone formation during tooth movement were examined using eight rabbits with denervation of inferior alveolar nerve (IAN). IAN on one side for all the animals was denervated and and sham operation was performed on the other side of denervation. The distance of tooth movement on the denervated and sham operated sides was very similar and 1.20 +/- 0.17 and 1.24 +/- 0.12 (mean +/- S.D. mm), respectively. From the fluorescent observations, the denervated and sham operated sides in the animals without tooth movement i.e. control group showed similar morphology. The animals with tooth movement i.e. experimental group showed significant new bone formation than the control group. However, the amount of new bone formation on the denervated side was less than the sham operated side. It was suggested that the nerve fibers might play some roles on bone formation during the tooth movement.

Alveolar Process↗

Purification and characterization of DNA topoisomerase IV in Escherichia coli.

The subunits of topoisomerase IV (topo IV), the ParC and ParE proteins in Escherichia coli, were purified to near homogeneity from the respective overproducers. They revealed type II topoisomerase activity only when they were combined with each other. In the presence of Mg2+ and ATP, topo IV was capable of relaxing a negatively or positively supercoiled plasmid DNA or converting the knotted P4 phage DNA, whether nicked or ligated, to a simple ring. However, supercoiling activity was not detected. The topoisomerase activity was not detectable when the purified ParC and ParE proteins were combined with the purified GyrB and GyrA proteins, respectively. This is consistent with the result that neither a parC nor a parE mutation was compensated by transformation with a plasmid carrying either the gyrA or the gyrB gene. Simultaneous introduction of both the gyrA and gyrB plasmids corrected the phenotypic defect of parC and parE mutants. The results suggest that DNA gyrase can substitute for topo IV at least in some part of the function for chromosome partitioning. Antisera were prepared against the purified ParC, ParE, GyrA, and GyrB proteins and used to investigate cellular localization of these gene products. ParC protein was found to be specifically associated with inner membranes only in the presence of DNA. This result suggests that one of the functions of topo IV might be to anchor chromosomes on membranes as previously proposed for eukaryotic topoisomerase II.

Bacterial Proteins↗

Human guanylin: cDNA isolation, structure, and activity.

Guanylin is a mammalian peptide homologue of heat-stable enterotoxins that acts on intestinal guanylate cyclase to elicit an increase in cyclic GMP. We have isolated a cDNA encoding an apparent precursor of guanylin from a human intestinal cDNA library. The mRNA is expressed at high levels in human ileum and colon. Human guanylin stimulated increases in T84 cell cyclic GMP levels, displaced 125I-labelled heat-stable enterotoxin (STa) binding to this cell line, and stimulated increases in short-circuit current (Isc) of isolated rat proximal colonic mucosa. This peptide may play a role in regulating fluid and electrolyte absorption in human intestines.

Amino Acid Sequence↗

Regional distribution of copper, zinc and iron in the brain in Long-Evans Cinnamon (LEC) rats with a new mutation causing hereditary hepatitis.

In Long-Evans Cinnamon (LEC) rats of three different ages (7, 13 and 32 weeks old) concentrations of Cu, Zn and Fe were measured in 8 regions of the brain. The LEC groups aged 7 and 13 weeks showed low concentrations of Cu in all regions compared to Long-Evans Agouti (LEA) rats. In 32-week-old LEC rats, however, Cu concentrations increased in 7 regions, in particular, significantly so in the striatum, hypothalamus, cerebellum, midbrain and cortex. Changes of Zn concentration were not found in any region. The Fe concentration increased in cortex and olfactory lobes. The three LEC groups showed a very high concentration of hepatic Cu and a low concentration of serum Cu compared to LEA rats. In LEC rats aged 32 weeks, however, hepatic Cu decreased and serum Cu increased compared to the other two LEC groups. These results suggest that the increase of the cerebral Cu concentration is closely related to the inherently abnormal Cu metabolism and then to the changes of Cu metabolism from about 13 weeks after birth.

Animals↗

Rat guanylin cDNA: characterization of the precursor of an endogenous activator of intestinal guanylate cyclase.

Guanylin is a recently discovered endogenous activator of intestinal guanylate cyclase that was purified from intestinal tissue. Clones have been isolated which demonstrate that the guanylin peptide is contained within a 115 amino acid apparent preprohormone encoded by a 600 base messenger RNA in rat jejunum. The messenger RNA is found predominantly in intestinal tissues, showing a striking gradient of expression ranging from undetectable in esophagus and stomach to abundant in colon. Guanylin may serve a paracrine function to regulate intestinal guanylate cyclase activity, cyclic GMP levels, and thereby, fluid and electrolyte absorption. We hypothesize that the heat stable enterotoxins mimic the endogenously produced guanylin to cause diarrhea.

Amino Acid Sequence↗

Growth-stimulatory monoclonal antibodies against human insulin-like growth factor I receptor.

Monoclonal antibodies (mAbs) against purified human placental insulin-like growth factor I (IGF-I) receptors were prepared and characterized. Three IgG mAbs were specific for the human IGF-I receptor and displayed negligible crossreactivity with the human insulin receptor. They stimulated 125I-labeled IGF-I (125I-IGF-I) or 125I-IGF-II binding to purified human placental IGF-I receptors and to IGF-I receptors expressed in NIH 3T3 cells in contrast to the well-studied mAb alpha IR-3, which inhibits 125I-IGF-I or 125I-IGF-II binding to both forms of IGF-I receptors. The mAbs introduced in this study stimulated DNA synthesis in NIH 3T3 cells expressing human IGF-I receptors approximately 1.5-fold above the basal level and the IGF-I- or IGF-II-stimulated level. In contrast, alpha IR-3 inhibited both basal and IGF-I or IGF-II-stimulated DNA synthesis by approximately 30%. Inhibition of IGF-II-stimulated DNA synthesis by alpha IR-3 was as potent as its inhibition of IGF-I-stimulated DNA synthesis, although IGF-II binding to the IGF-I receptors was not inhibited by IGF-II as potently as was IGF-I. With the purified IGF-I receptors, both inhibitory and stimulatory mAbs were shown to activate autophosphorylation of the IGF-I receptor beta subunit and to induce microaggregation of the receptors. These results suggest that conformational changes resulting from receptor dimerization in the presence of either type of mAb may affect the signal-transducing function of the IGF-I receptor differently. These additional mAbs and alpha IR-3 immunoprecipitated nearly 90% of IGF-I binding activity from Triton X-100-solubilized human placental membranes, indicating that IGF-I receptor reactive with these mAbs is the major form of the IGF-I receptor in human placenta.

3T3 Cells↗

The effects of morphine administered into the vertebral artery on the somatosympathetic A- and C-reflexes in anesthetized cats.

The effects of morphine (0.2-200 micrograms/kg) administered into the brain stem via a vertebral artery on the somatosympathetic A- and C-reflexes evoked in a cardiac sympathetic nerve by electrical stimulation of somatic myelinated (A) and unmyelinated (C) afferent nerve fibers in anesthetized cats were examined. The intravertebral arterial administration of 20-200 micrograms/kg morphine depressed dose-dependently both the somatosympathetic A- and C-reflexes. Following the administration of 200 micrograms/kg morphine, the amplitudes of the sympathetic A- and C-reflexes were depressed to 71 +/- 8% and 80 +/- 8% of the control magnitude, respectively. Injection of 2-200 micrograms/kg morphine caused hypotension in a dose-dependent manner. It is concluded that morphine administered in the brain stem via the vertebral artery produced a nonselective and slight depression of both the somatosympathetic A- and C-reflexes by acting at the level of brain stem.

Anesthesia↗

Suppression of atrial natriuretic peptide (ANP) receptor recovery from homologous down-regulation by 8-bromo-cGMP in endothelial cells.

In a previous study we reported that cyclic GMP (cGMP) selectively down-regulates the atrial natriuretic peptide clearance receptor (C-ANP receptor) in the cultured bovine pulmonary artery endothelial (CPAE) cell line. Our efforts in the current study are directed towards determining the effects of cGMP on C-ANP receptor recycling and de novo synthesis following homologous down-regulation by atriopeptin III (APIII, rat ANP 103-126). [125I]APIII binding to CPAE cells was decreased to 45.3 +/- 1.0% of control following the pretreatment with 100 nM APIII for 24 h. After the removal of APIII, the decreased [125I]APIII binding gradually recovered up to 68.8 +/- 1.8% of control for 24 h: a 'long-term recovery'. When CPAE cells were pretreated with 1 nM APIII for 30 min, [125I]APIII binding was also decreased to 62.6 +/- 2.6% of control. Following the removal of APIII, the decrease in [125I]APIII binding quickly recovered to 87.7 +/- 2.7% of control for 1 h: a 'short-term recovery'. 8-bromo-cGMP suppressed the long-term recovery of ANP receptor in a dose-dependent manner, while it had no effect on the short-term recovery. Both actinomycin D (1 ng/ml) and cycloheximide (10 ng/ml) significantly (P less than 0.01) suppressed the long-term recovery, but failed to affect the short-term recovery, whereas, the short-term recovery was significantly (P less than 0.01) inhibited by either 10 mM NH4Cl or 0.2 mM chloroquine which inhibits the recycling of internalized ANP receptor. These findings suggest that new ANP receptor synthesis is necessary for long-term but not for short-term recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

Guanylin: an endogenous activator of intestinal guanylate cyclase.

Intestinal guanylate cyclase mediates the action of the heat-stable enterotoxin to cause a decrease in intestinal fluid absorption and to increase chloride secretion, ultimately causing diarrhea. An endogenous ligand that acts on this guanylate cyclase has not previously been found. To search for a potential endogenous ligand, we utilized T84 cells, a human colon carcinoma-derived cell line, in culture as a bioassay. This cell line selectively responds to the toxin in a very sensitive manner with an increase in intracellular cyclic GMP. In the present study, we describe the purification and structure of a peptide from rat jejunum that activates this enzyme. This peptide, which we have termed guanylin, is composed of 15 amino acids and has the following amino acid sequence, PNTCEICAYAACTGC, as determined by automated Edman degradation sequence analysis and electrospray mass spectrometry. Analysis of the amino acid sequence of this peptide reveals a high degree of homology with heat-stable enterotoxins. Solid-phase synthesis of this peptide confirmed that it stimulates increases in T84 cyclic GMP levels. Guanylin required oxidation for expression of bioactivity and subsequent reduction of the oxidized peptide eliminated the effect on cyclic GMP, indicating a requirement for cysteine disulfide bond formation. Synthetic guanylin also displaces heat-stable enterotoxin binding to cultured T84 cells. Based on these data, we propose that guanylin is an activator of intestinal guanylate cyclase and that it stimulates this enzyme through the same receptor binding region as the heat-stable enterotoxins.

Amino Acid Sequence↗

Inhibition of endothelial cell clearance of atrial natriuretic peptide by cyclic GMP treatment.

In a previous study, we reported that cyclic GMP (cGMP) selectively down-regulates the clearance receptor (C-receptor) for atrial natriuretic peptide (ANP) in the cultured bovine pulmonary artery endothelial (CPAE) cell line. The present study was undertaken in order to examine the effect of cGMP on the internalization of the ANP-receptor complex in CPAE cells. Maximum binding of [125I]APIII to the cells significantly decreased following the treatment with 1 mM 8-bromo-cGMP for 48 or 72 h. Scatchard analysis of the binding assay data from the treated cells showed a decrease in Bmax (616 to 411 fmol/mg protein) without a significant change in Kd. Removal of cell surface-bound APIII by acetic acid revealed that not only the surface binding, but also the internalization of APIII significantly decreased in 8-bromo-cGMP-treated cells, indicating a decrease in receptor-mediated uptake of ANP into the cells. These results suggest that cGMP regulates the clearance of ANP by vascular endothelial cells.

Analysis of Variance↗

Antitumor activity of basic fibroblast growth factor-saporin mitotoxin in vitro and in vivo.

Many cancer cell lines express basic fibroblast growth factor (FGF) receptors, making them potential targets for the delivery of FGF-based cytotoxic compounds. To this end, we have investigated the antitumor activity of a novel mitotoxin, Fibroblast Growth Factor-saporin (FGF-SAP), a conjugate of FGF and the ribosome-inactivating protein, saporin. In vitro, FGF-SAP is cytotoxic for human melanoma, teratocarcinoma, and neuroblastoma cells expressing FGF-receptors. Mice treated with FGF-SAP i.v., on a variety of schedules, showed dramatic tumor growth inhibition with minimal toxicity. Thus, FGF-SAP appears to be a well-tolerated and potent antitumor agent. The potential of FGF-targeted cytotoxicity is discussed.

Animals↗

Systemic administration of procaine suppresses the somato-sympathetic reflex discharges in anesthetized cats.

Somato-sympathetic reflex discharges (SSRDs) which were induced from the lumbar sympathetic truck elicited by train pulse stimulation of femoral nerves in anesthetized cats were examined during and after intravenous infusion of 1 mg.kg(-1).min(-1) of procaine. The infusion demonstrated that amplitudes were suppressed with prolonged latencies and/or their tendencies in A- and C-reflex potentials of SSRDs. Heart rate and blood pressure decreased slightly, and the decreases correlated with time courses of suppressed SSRDs. These results suggest that the systemic procaine infusion may be a reliable method to alleviate somato-sympathetic reflexes under such conditions as extreme stimulation of somatic afferent nerves observed in surgical procedures.

Journal Article↗