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Biomedical subjects

F Suzuki

Publications and source records attributed to F Suzuki.

At least 469 records · Page 26Linked to original sources

Differential effects of parathyroid hormone and somatomedin-like growth factors on the sizes of proteoglycan monomers and their synthesis in rabbit costal chondrocytes in culture.

In the proteoglycans extracted from rabbit costal chondrocytes in culture, two populations of proteoglycans were distinguished by density gradient centrifugation under dissociative conditions. The major component was the faster sedimenting population (proteoglycan I), the putative 'cartilage-specific' proteoglycans, and the minor component was the slower sedimenting population (proteoglycan II). The monomeric size of proteoglycan I was closely related to the differentiation-state of chondrocytes and was a good marker of the differentiated chondrocytes. Treatment of the cultures with parathyroid hormone (PTH) induced an increase in the monomeric size of proteoglycan I. This increase was ascribed to an increase in the molecular size of the glycosaminoglycan chain in proteoglycan I. On the other hand, somatomedin-like growth factors, such as multiplication-stimulating activity (MSA) and cartilage-derived factor (CDF), did not affect the size of proteoglycan I, while they markedly stimulated the synthesis of proteoglycan I. In contrast, treatment with nonsomatomedin growth factors, such as fibroblast growth factor (FGF) and epidermal growth factor (EGF), resulted in not only a decrease in glycosaminoglycan synthesis but also a slight decrease in size of proteoglycan I. However, synthesis and size of proteoglycan II were little affected by these agents. Thus, the present study clearly shows that PTH and somatomedin-like growth factors have differential functions in bringing about the expression of the differentiated phenotype of chondrocytes: PTH influences chain elongation and termination of glycosaminoglycans in proteoglycan I, while somatomedin-like growth factors affect primarily the synthesis and secretion of proteoglycan I.

Animals↗

Inhibition of adipose S-100 protein release by insulin.

The release of S-100 protein brought about in rat epididymal fat pads by 10 microM epinephrine was inhibited by about 50% in the presence of more than 8 nM insulin. The inhibitory effect of insulin was also observed in the release of S-100 protein induced by isoproterenol or adrenocorticotropin (ACTH), but not in the release induced by a high concentration (5 mM) of dibutyryl cyclic AMP. Since insulin suppressed (to about 50%) the increase in cyclic AMP content induced by epinephrine under the same conditions, it is suggested that the inhibitory mechanism is mediated by the cyclic AMP levels in adipocytes. The S-100 protein release induced by catecholamine was significantly decreased (to about 50%) in the fat pads obtained from insulin-injected rats. In contrast, in the fat pads obtained from diabetic or long-term starved rats, the S-100 protein release was greatly enhanced, showing several-fold higher levels of basal release in the absence of hormones, and S-100 protein contents in the epididymal adipose tissues of these rats were significantly lower than those of the control rats. These results suggest that the S-100 protein content in adipocytes is regulated by insulin as well as the lipolytic hormones.

Adipose Tissue↗

Maturation of spermatozoa in the epididymis of the Chinese hamster.

Chinese hamster spermatozoa gain their ability to move when they descend from the testis to the distal part of the caput epididymis, but it is not until they enter the corpus epididymis that they become capable of fertilizing eggs. The maturation of the spermatozoa proceeds as they further descend the tract and perhaps continues even in the vas deferens. During transit between the distal caput and proximal cauda epididymides, small membrane-limited vesicles (and tubules) appear on the plasma membrane over the acrosomes of the spermatozoa. The number of vesicles appearing on the sperm brane reaches a maximum when the spermatozoa are in the proximal cauda epididymis. It declines sharply in the distal cauda epididymis. Spermatozoa in the vas deferens are free of the vesicles. The origin, chemical nature, and functional role of the vesicles that appear on the sperm surface during epididymal transit must be the subject of further investigation.

Animals↗

Determination of methionine sulfoxide in protein and food by hydrolysis with p-toluenesulfonic acid.

Methionine sulfoxide in peptides and proteins was determined by use of 3 N p-toluenesulfonic acid as a hydrolyzing agent. Samples were hydrolyzed at 110 degrees C for 22 h in an evacuated sealed tube and analyzed for amino acid content. Amino acid analysis showed that the recovery of methionine sulfoxide from a synthetic peptide and its mixture with proteins was consistently better than 90%. The recovery of all other amino acids except tryptophan was complete, and was similar to that observed after hydrolysis with 6 N HCl. The presence of carbohydrates had no effect on the yield. Thus, the present procedure can be used for general and simultaneous determination of methionine sulfoxide as well as other amino acids in proteins.

Amino Acids↗

Cartilage-derived anti-tumor factor (CATF) inhibits the proliferation of endothelial cells in culture.

Previous studies showed that a cartilage-derived anti-tumor factor (CATF), which was extracted from bovine cartilage with 1 M guanidine hydrochloride, inhibited the growth of solid sarcoma 180, but not the growth of ascites tumors of sarcoma 180 [Suzuki, F. et al. Jpn. J. Bone Metab., 2, 231-235 (1984)]. This study showed that CATF inhibited the proliferation and DNA synthesis of endothelial cells isolated from bovine pulmonary artery, but not the proliferations of sarcoma 180, L1210 and L cells. These results suggest that CATF has anti-angiogenic properties, thereby inhibiting the growth of solid tumors.

Animals↗

Ability of sera from mice treated with Ge-132, an organic germanium compound, to inhibit experimental murine ascites tumours.

Sera from C57Bl/6 mice treated orally with Ge-132 exhibited antitumour activity against Ehrlich (allogeneic) and RL male 1 (syngeneic) ascites tumours in BALB/c mice. Sera obtained from mice 24 h after Ge-132 administration displayed the greatest antitumour effect and this was dose dependent. Sera prepared from mice 12, 36, or 48 h after Ge-132 treatment had no protective effect. Circulating interferon (IFN) was induced at 24 h after administration of Ge-132 but was not detected in the sera at 12, 36, or 48 h after administration. The antiviral activity of sera from Ge-132-treated mice was inactivated by treatments with trypsin, low pH, and anti-IFN gamma antiserum. The inactivated preparations of serum IFN induced by Ge-132 did not exhibit antitumour activity when administered to tumour-bearing mice. These results suggest that antitumour activity in the sera of Ge-132-treated mice may be expressed through activities of Ge-132-induced lymphokine(s), such as IFN gamma.

Animals↗

Induction of spermidine/spermine N1-acetyltransferase by parathyroid hormone in rabbit costal chondrocytes in culture.

Parathyroid hormone (PTH) increased the activity of spermidine/spermine N1-acetyltransferase, a rate-limiting enzyme of polyamine biodegradation, in rabbit costal chondrocytes in culture. The enzyme activity increased in a dose-dependent manner after addition of PTH to the culture, reaching a maximum at 8 h. The increase in the enzyme activity was abolished by cycloheximide or actinomycin D. Dibutyryl cyclic AMP also induced the acetyltransferase to some extent. These results suggest that the induction of spermidine/spermine N1-acetyltransferase by PTH may play some significant role in the expression of the differentiated phenotype of chondrocytes.

Acetyltransferases↗

Stimulation by glucocorticoids of the differentiated phenotype of chondrocytes and the proliferation of rabbit costal chondrocytes in culture.

Hydrocortisone stimulated glycosaminoglycan (GAG) synthesis, a characteristic of the cartilage phenotype, of rabbit costal chondrocytes in confluent quiescent culture, as judged by the incorporations of [35S]sulfate and [3H]glucosamine. Hydrocortisone also stimulated incorporation of [3H]serine into proteoglycan. The stimulation of GAG synthesis by hydrocortisone was dose-dependent and maximal at a physiological concentration of 10(-7) M. Hydrocortisone also stimulated GAG synthesis in cultures in the log-phase of growth. In this case, its maximal effect was observed at a concentration of 10(-6) M. The magnitude of the increase of GAG synthesis in response to hydrocortisone was larger in confluent culture than in log-phase cultures. Hydrocortisone stimulated DNA synthesis dose-dependently, and its effect was observable at a physiological concentration. However, no stimulation of DNA synthesis by hydrocortisone was observed in serum-free medium, in contrast to that of GAG synthesis. Hydrocortisone also increased protein synthesis and the cell number. Dexamethasone also stimulated the syntheses of both GAG and DNA. These results show that glucocorticoids stimulated both the differentiated phenotype of chondrocytes and the proliferation of rabbit costal chondrocytes in culture. Moreover, the effect of glucocorticoids was primarily on the differentiated phenotype of chondrocytes and its effect on proliferation was permissive.

Animals↗

Induction of interferon and activation of NK cells and macrophages in mice by oral administration of Ge-132, an organic germanium compound.

After oral administration of an organic germanium compound, Ge-132 (300 mg/kg), a significant level of interferon (IFN) activity was detected in the sera of mice at 20 hr and it reached a maximum of 320 U/ml at 24 hr. This IFN activity was lost after heat- or acid-treatment, suggesting that the induced IFN is of gamma-nature. The molecular weight of this IFN was estimated to be 50,000 daltons by gel filtration. The NK activity of spleen cells was increased 24 hr after the oral administration of Ge-132, and cytotoxic macrophages were induced in the peritoneal cavity by 48 hr. In the mice receiving an intraperitoneal (ip) injection of trypan blue or carrageenan 2 days before oral administration of Ge-132, neither induction of IFN nor augmentation of NK activity occurred, and X-ray irradiation of mice also rendered the mice incapable of producing IFN, all indicating that both macrophages and lymphocytes are required for this IFN induction. Both NK and cytotoxic macrophages appeared 18 hr after ip administration of the induced IFN with a titer as low as 20 U/ml. These facts suggest that both the augmentation of NK activity and activation of macrophages in mice after oral administration of Ge-132 are mediated by the induced IFN.

Administration, Oral↗

Effects of synthetic analogs and fragments of bovine parathyroid hormone on adenosine 3',5'-monophosphate level, ornithine decarboxylase activity, and glycosaminoglycan synthesis in rabbit costal chondrocytes in culture: structure-activity relations.

Previously, we demonstrated that PTH increases the level of cAMP, the activity of ornithine decarboxylase (ODC; EC 4.1.1.17; which is a rate-limiting enzyme in polyamine biosynthesis), and glycosaminoglycan (GAG) synthesis (which is characteristic of the chondrocyte phenotype) in rabbit costal chondrocytes in culture. These studies suggested that the accumulation of cAMP and the induction of ODC by PTH are good markers of the differentiated phenotype of cultured chondrocytes. In the present study, the biological effects of a series of bovine PTH (bPTH) fragments and analogs on these three parameters of PTH action were examined. bPTH-(1-34), [Nle8,Nle18,Tyr34]bPTH-(1-34) amide and bPTH-(1-27) amide increased cAMP levels, ODC activity, and GAG synthesis in a dose-dependent manner over the concentration range of 10(-9)-10(-5) M. The order of decreasing potency was: bPTH-(1-34), [Nle8,Nle18,Tyr34]bPTH-(1-34) amide, and bPTH-(1-27) amide. On the other hand, [Nle8,Nle18,Tyr34]bPTH-(3-34) amide, bPTH-(5-27) amide, and [Tyr34]bPTH-(20-34) amide failed to increase cAMP levels, ODC activity, or GAG synthesis when present in concentrations up to 10(-5) M. However, [Nle8,Nle18,Tyr34]bPTH-(3-34) amide, bPTH-(5-27) amide, and [Tyr34]bPTH-(20-34) amide inhibited bPTH-(1-34)-stimulated increases in cAMP and ODC activity. These results partially define the principal structural determinants within the PTH molecule required for biological activity and expression of the differentiated phenotype of chondrocytes.

Animals↗

Usefulness of invasive and non-invasive electrophysiologic studies in the selection of antiarrhythmic drugs for the patients with paroxysmal supraventricular tachyarrhythmia.

A comparison of the effects of several antiarrhythmic agents was made in a study of 70 patients - 15 with manifest Wolff-Parkinson-White (WPW) syndrome, 17 with concealed WPW syndrome, 18 with AV nodal re-entrant tachycardia, 14 with paroxysmal atrial fibrillation and 6 with paroxysmal atrial flutter - employing intracardiac stimulation and esophageal pacing. For the termination of paroxysmal supraventricular tachycardia, intravenous administration of verapamil or aprindine was more effective than that of disopyramide or procainamide. In AV nodal re-entrant tachycardia, verapamil was the most effective for termination. In the manifest WPW syndrome, disopyramide or aprindine was indicated especially for patients with the accessory pathways of the short antegrade refractory period, because these drugs lengthened the refractory period of the accessory pathways. For the purpose of converting atrial fibrillation or flutter to the sinus rhythm, type IA drugs such as disopyramide were indicated. However, verapamil was effective for slowing down the ventricular rate in atrial fibrillation or flutter except in cases of manifest WPW syndrome. A 6-month follow-up study showed that oral administration of verapamil was also useful for putting a stop to the attacks in 24 out of 32 patients with paroxysmal supraventricular tachycardia, while oral disopyramide prevented the recurrence of atrial fibrillation in only 4 of 10 patients.

Administration, Oral↗

A new method for assessing ventriculoatrial conduction in the human heart.

The presence or absence of ventriculoatrial (VA) conduction in the human heart is assessed by investigating whether 1:1 retrograde atrial capture is observed during constant cycle length ventricular pacing. In this study, a new pacing protocol for assessing VA conduction was designed in which the ventricular extrastimulus was delivered during basic ventricular and atrial simultaneous pacing (VE-VASP method). The effect of this pacing protocol on VA conduction was investigated in 12 patients who showed no evidence of VA conduction with the constant cycle length ventricular pacing method. In 5 of 12 patients, intact VA conduction was demonstrated with the VE-VASP method, while VA conduction was not observed in the remaining 7 patients. These results suggest that VE-VASP method sometimes demonstrates the presence of intact VA conduction in patients who show no evidence of VA conduction during constant cycle length ventricular pacing.

Adult↗

Active site of intestinal gamma-glutamyltransferase faces luminal side of brush border membrane.

Purified gamma-glutamyltransferase from hog small intestine was competitively inhibited by glutathione in vitro when L-gamma-glutamyl-p-nitroanilide was used as a substrate. An S-acetyldextran derivative of glutathione inhibited the enzyme as well as glutathione, although dextran had no inhibitory effect. gamma-Glutamyltransferase in the rat small intestine could utilize in situ L-gamma-glutamyl-p-nitroanilide circulated in the lumen, and was inhibited by the impermeable derivative of glutathione which was on the luminal side. These data suggested that the active site of intestinal gamma-glutamyltransferase faced the luminal side of the brush border membrane.

Aniline Compounds↗

Differentiation and de-differentiation of cultured chondrocytes: increase in monomeric size of 'cartilage-specific' proteoglycans by dibutyryl cyclic AMP and complete inhibition of their synthesis by retinoic acid.

Dibutyryl cyclic AMP (DBcAMP) induced an increase in the monomeric size of 'cartilage-specific' proteoglycans (PG-I) in rabbit costal chondrocytes in culture. This increase in size was due to an increase in the average molecular weight of the glycosaminoglycan (GAG) chains. In contrast, retinoic acid completely inhibited the synthesis of PG-I. However, the synthesis and monomeric size of 'ubiquitous' proteoglycans (PG-II) were little affected by these agents. These results suggested that modulation of the differentiated state of chondrocytes is closely related to not only the synthesis of 'cartilage-specific' proteoglycans but also their monomeric size.

Animals↗