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Biomedical subjects

F Suzuki

Publications and source records attributed to F Suzuki.

At least 253 records · Page 14Linked to original sources
PubMed1994

Cell-type-specific expression and regulation of a c-fos-NGF fusion gene in neurons and astrocytes of transgenic mice.

A mouse line transgenic for nerve growth factor (NGF) was developed using the mouse prepro-NGF cDNA inserted within a plasmid containing the proximal region (-10 to -550 bp) of the c-fos promoter and the transcription termination and polyadenylation signals of the rabbit beta-globin gene. No significant modification of gross behavior or central nervous system anatomy was detected in adult animals as assessed by immunohistochemistry and in situ hybridization for NGF and choline acetyltransferase. The expression of the transgene and the possible regulation of its expression by agents acting on the promoter were investigated in vitro. Despite the presence of an additional pool of NGF mRNA specific to the transgene, basal levels of NGF in the supernatant of transgenic astrocytes were similar to normal ones. On the other hand, transgenic neurons spontaneously synthesized and released levels of NGF two to three times higher than normal neurons, while mRNA levels were barely detectable by conventional Northern blotting. The tissue-specificity of NGF expression was respected, with higher levels in hippocampal than neocortical neurons. Increases of NGF mRNA by agents acting on the promoter could be observed in normal and transgenic astrocytes only after inhibition of the protein synthesis by cycloheximide, suggesting a similar rapid turnover of normal and transgenic transcripts. Cyclic AMP agonists specifically increased the secretion of NGF protein by transgenic astrocytes and neurons, while activators of the protein kinase C had a similar effect on transgenic and normal cells. Differences between amounts of NGF secreted by neurons and astrocytes with regards to their respective content in mRNA suggest that transgenic transcripts are subject to normal cell- and tissue-specific post-transcriptional regulations. Agents acting on the c-fos promoter through the protein kinase C or cyclic AMP routes differentially increased the secretion of NGF by transgenic astrocytes or neurons, supporting this hypothesis.

Animals↗
PubMed1994

Effects of a traditional Chinese herbal medicine, Kanzo-bushi-to, on the resistance of thermally injured mice infected with herpes simplex virus type 1.

The protective effect of Kanzo-bushi-to (TJS-038) was investigated on the opportunistic infection of herpes simplex virus type 1 (HSV) in thermally injured mice (TI-Mice). We have previously reported that TI-Mice were approximately 100 times more susceptible to HSV infection than normal mice (N-Mice) and that CD8+ suppressor T (ST)-cells induced by burn injury were involved in causing this increased susceptibility of TI-Mice. Increased susceptibility of TI-Mice to the infection was reversed to the levels observed in N-Mice when TI-Mice were treated intraperitoneally with TJS-038 at a dose of 5 mg/kg 1 and 4 days after thermal injury. The activity of ST-cells was greatly decreased in TI-Mice treated with TJS-038. The generation of Vicia villosa lectin-adherent CD4+ CD28+ TCR-alpha/beta+ contrasuppressor T (Contra-ST)-cells associated with the appearance of ST-cells was expanded and occurred earlier in spleens of TJS-038-treated TI-Mice as compared with that of untreated TI-Mice. The improved resistance of TJS-038-treated TI-Mice to the infection was transferred to untreated TI-Mice by adoptive transfer of Contra-ST-cells prepared from TJS-038-treated TI-Mice. These results suggest that TJS-038 may restore the resistance of TI-Mice to the HSV infection through the expanded generation of Contra-ST-cells.

Animals↗
PubMed1994

T wave "humps" as a potential electrocardiographic marker of the long QT syndrome.

OBJECTIVES: This study attempted to determine the prevalence and electrocardiographic (ECG) lead distribution of T wave "humps" (T2, after an initial T wave peak, T1) among families with long QT syndrome and control subjects. BACKGROUND: T wave abnormalities have been suggested as another facet of familial long QT syndrome, in addition to prolongation of the rate-corrected QT interval (QTc), that might aid in the diagnosis of affected subjects. METHODS: The ECGs from 254 members of 13 families with long QT syndrome (each with two to four generations of affected members) and from 2,948 healthy control subjects (age > or = 16 years, QTc interval 0.39 to 0.46 s) were collected and analyzed. Tracings from families with long QT syndrome were read without knowledge of QTc interval or family member status (210 blood relatives and 44 spouses). RESULTS: We found that T2 was present in 53%, 27% and 5% of blood relatives with a "prolonged" (> or = 0.47 s, "borderline" (0.42 to 0.46 s) and "normal" (< or = 0.41 s) QTc interval, respectively (p < 0.0001), but in only 5% and 0% of spouses with a borderline and normal QTc interval, respectively (p = 0.06 vs. blood relatives). Among blood relatives with T2, the mean [+/- SD] maximal T1T2 interval was 0.10 +/- 0.03 s and correlated with the QTc interval (p < 0.01); a completely distinct U wave was seen in 23%. T2 was confined to leads V2 and V3 in 10%, whereas V4, V5, V6 or a limb lead was involved in 90% of blood relatives with T2. Among blood relatives with a borderline QTc interval, 50% of those with versus 20% of those without major symptoms manifested T2 in at least one left precordial or limb lead (p = 0.05). A T2 amplitude > 1 mm (grade III) was observed, respectively, in 19%, 6% and 0% of blood relatives with a prolonged, borderline and normal QTc interval with T2 in at least one left precordial or limb lead. Among the 2,948 control subjects, 0.6% exhibited T2 confined to leads V2 and V3, and 0.9% had T2 involving one or more left precordial lead (but none of the limb leads). Among 37 asymptomatic adult blood relatives with QTc intervals 0.42 to 0.46 s, T2 was found in left precordial or limb leads in 9 (24%; 5 with limb lead involvement) versus only 1.9% of control subjects with a borderline QTc interval (p < 0.0001). CONCLUSIONS: These findings are consistent with the hypothesis that in families with long QT syndrome, T wave humps involving left precordial or (especially) limb leads, even among asymptomatic blood relatives with a borderline QTc interval, suggest the presence of the long QT syndrome trait.

Adolescent↗
PubMed1994

Nephrocalcin in patients with renal cell carcinoma.

Nephrocalcin, an acidic glycoprotein that inhibits calcium oxalate crystal growth, has been previously localized in proximal tubules of kidneys by an immunohistochemical staining method and purified from tissue culture media of 2 renal carcinoma cell lines. A polyclonal antibody specific to nephrocalcin was raised in rabbits and the level of nephrocalcin was quantitatively determined in urine of 19 renal cell carcinoma patients (0.241 +/- 0.341 microgram nephrocalcin per mg. creatinine) and compared to healthy controls (0.022 +/- 0.012 micrograms nephrocalcin per mg. creatinine). Nephrocalcin levels after tumor nephrectomy decreased dramatically in 5 patients and to a lesser degree in 7. A specific nephrocalcin fraction that was eluted from an anion exchange column with low ionic strength was detected in urine of the renal cell carcinoma patients, and this fraction decreased or disappeared after tumor nephrectomy in 6 of 9 patients studied. Amino acid composition, phosphate content and dissociation constants toward calcium oxalate monohydrate crystals were investigated in the nephrocalcin from tumor patients and compared to that from healthy controls. Our studies demonstrate that nephrocalcin in patients with renal cell carcinoma is atypical and usually in much higher quantity. Further studies are needed to determine the clinical significance of these observations.

Biomarkers, Tumor↗
PubMed1994

Sperm-egg recognition in the mouse: characterization of sp56, a sperm protein having specific affinity for ZP3.

Recognition between mammalian gametes occurs when the plasma membrane of the sperm head binds to the zona pellucida (ZP), an extracellular coat surrounding eggs. ZP3, one of three glycoproteins in the ZP, is the egg protein recognized by sperm. A mouse sperm surface protein, sp56 (M(r) = 56,000), has been identified on the basis of its specific affinity for ZP3 (Bleil, J. D., and P. M. Wassarman. 1990. Proc. Natl. Acad. Sci. USA. 87:5563-5567). Studies presented here were designed to characterize mouse sperm sp56 and to further test whether or not this protein specifically recognizes ZP3. sp56 was purified by both ZP3 affinity chromatography and by ion exchange chromatography followed by size-exclusion chromatography. The purified native protein eluted from size-exclusion columns as a homomultimer (M(r) approximately 110,000). Each monomer of the protein contains intramolecular disulfide bonds, consistent with its extracellular location. Immunohistochemical and immunoblotting studies, using monoclonal antibodies, demonstrated that sp56 is a peripheral membrane protein located on the outer surface of the sperm head plasma membrane, precisely where sperm bind ZP3. Results of crosslinking experiments demonstrated that the ZP3 oligosaccharide recognized by sperm has specific affinity for sp56. Collectively, these results suggest that sp56 may be the sperm protein responsible for sperm-egg recognition in the mouse.

Amino Acid Sequence↗
PubMed1994

Double ventricular responses during extrastimulation of atrioventricular nodal reentrant tachycardia.

In patients with dual atrioventricular (AV) nodal pathways, double ventricular responses to a single atrial depolarization have been shown to occur, but virtually only during atrial pacing in sinus rhythm. We report on a patient with a slow-fast form of AV nodal reentrant tachycardia who exhibited double ventricular responses following extrastimulation during AV nodal reentrant tachycardia. The phenomenon of double ventricular responses during the tachycardia was demonstrated by extrastimulation from the proximal coronary sinus. Retrograde unidirectional block in the slow pathway, and an anterograde effective refractory period that was shorter in the fast pathway than that in the slow pathway, are suggested.

Atrioventricular Node↗
PubMed1994

Proto-oncogene expression in a human chondrosarcoma cell line: HCS-2/8.

HCS-2/8 is a stable human chondrosarcoma cell line with many chondrocytic characteristics and has the capacity to form chondrosarcomas in nude mice. The cells display both biochemically and morphologically definable changes in sparse, subconfluent, confluent and over-confluent phases of in vitro culture. Such features of HCS-2/8 cells may reflect the processes of both proliferation and differentiation of chondrocytes in vivo. We examined the correlations of these changes of HCS-2/8 cells with their transcript levels of 21 proto-oncogenes by Northern analysis. We found no detectable transcripts of 9 proto-oncogenes (c-sis, c-met, c-src, c-lyn, c-fgr, c-ros, c-pim, Blym and N-myc), but detected transcripts of 12 other proto-oncogenes (int-2, erbB, c-abl, c-raf-1, c-fyn, K-ras, H-ras, c-mos, c-myc, c-myb, c-fos, and c-jun). In the over-confluent phase, the levels of c-fos and c-raf-1 were increased several dozen times and about 5 times, respectively, while the level of c-abl was about 1/5th of that in the sparse, subconfluent and confluent phases of culture. The level of int-2 increased about 10-fold in the confluent and over-confluent phases of in vitro culture. The transcript levels of c-mos and K-ras were high in the sparse phase, low in the subconfluent and confluent phases and high in the over-confluent phase. The levels of the other 6 proto-oncogenes in HCS-2/8 cells were constant in all phases of in vitro culture.

Chondrosarcoma↗
PubMed1994

The response of atrioventricular junctional tissue to temperature.

To determine the optimal temperature for catheter heat mapping without damaging cardiac tissue, we studied the electrophysiologic and histologic responses of the atrioventricular (AV) conduction system exposed to a specific range of temperatures. In 18 closed-chest dogs, an electrode catheter with a thermistor, tip was positioned transvenously at the AV junction. Radiofrequency current (RFC) was applied in incremental temperature steps until transient 2nd-degree AV block was induced. Catheter tip temperature (CTT) was measured at each step. RFC was immediately discontinued when AV block occurred. AV conduction was evaluated before and 4 weeks after the procedure. Acute transient 2nd-degree AV block was induced in 45 applications, during which the average CTT was 48.7 +/- 2.7 degrees C. In another 40 applications in which 2nd degree AV block was not induced, the average CTT was significantly lower [46.3 +/- 2.5 degrees C] (p < 0.001). Eleven of 16 dogs showed acute 2nd-degree AV block, but had normal AV conduction at 4 weeks (Group A). In the other 5 dogs, 1st-degree AV block was seen at 4 weeks (Group B). The lowest CTTs in Groups A and B were 45 and 49 degrees C, respectively. Histologic findings in 2 dogs from Group A revealed that 10-15% (by area) of the AV node was fibrotic. These findings suggest that the induction of fully reversible AV block can be achieved by titration of RFC, during the application of RFC to the AV junction. In conclusion, RF energy was used to produce a tip temperature of between 45 degrees C and 49 degrees C, which induced reversible and significant interruption of conduction of in tissue in the AV junction, and presumably also in target sites in clinical RF ablation.

Animals↗
PubMed1994

Sequencing and expression of sheep angiotensinogen cDNA.

A sheep liver cDNA library was screened with a BstEII fragment of human angiotensinogen cDNA to obtain sheep angiotensinogen cDNA. The cDNA sequence showed that preangiotensinogen consisted of 452 amino acid residues (49 kDa) of angiotensinogen and 24 residues of a signal peptide. Recombinant sheep angiotensinogen (56 kDa) was expressed in COS-7 cells.

Amino Acid Sequence↗
PubMed1994

[Effect of concanavalin A on morphology and DNA synthesis of resting chondrocyte cultures].

Rabbit chondrocytes were isolated from resting cartilage of ribs of 4-week-old New Zealand rabbits. Chondrocytes were seeded at low density and grown to confluency in medium (DME) with 10% fetal bovine serum, 50 micrograms/ml ascorbic acid, and antibiotics, at 37 degrees C under 5% CO2 in air, and then serum concentration was reduced to 0.3%. At the low serum concentration, chondrocytes adopted fibroblastic morphology. Addition of concanavalin A to the culture medium induced a morphologic alteration of the fibroblastic cells to polygonal or spherical chondrocytes that were surrounded by refractile matrix. Wheat germ agglutinin and garden pea lectin induced similar cell shape changes without any increase in matrix synthesis. Concanavalin A decreased [3H]thymidine incorporation into DNA in a dose-dependent manner with an ED50 of 0.4-1 micrograms/ml in the presence of various concentrations of serum ranging from 0.3 to 20%. The concanavalin A inhibition of DNA synthesis was abolished by 10 mmol/L methyl-D-mannopyranoside. The inhibition of chondrocyte proliferation does not seem to be specific to concanavalin A. Wheat germ agglutinin, lentil lectin, phytohemagglutinin, Ulex europeaus agglutinin, and garden pea lectin also decreased, dose-dependently, [3H]thymidine incorporation into DNA in chondrocytes. Other lectins at 0.01-20 micrograms/ml had little effect on [3H] thymidine incorporation. Because the molecular structure of concanavalin A and its mode of actions have been extensively characterized, chondrocytes exposed to this lectin will be useful as a novel model in studying of the control of cellular differentiation.

Animals↗
PubMed1994

[Deterioration of liver function following endoscopic injection sclerotherapy of esophageal varices--significance of a new index for liver function "delta TB"].

Changes of liver functions associated with endoscopic injection sclerotherapy (EIS) in which less than 6 ml of 5% ethanolamin oleate was used were investigated in 50 patients with remarkable esophageal varices. The index used for evaluating hepatic reserve was the difference of total bilirubin in serum between immediately and 15 hours after EIS and was tentatively named as "delta TB" (normal range < or = 0.1). In the patients classified as Child-Pugh A (n = 25), Child-Pugh B (n = 19) and Child-Pugh C (n = 6), delta TB was 0.04 +/- 0.30, 0.23 +/- 0.41, and 0.54 +/- 0.21, respectively. One month after the entire sessions of EIS, the changes of liver function tests before and after EIS were compared in 45 cases. It was disclosed that delta TB was elevated in parallel with the severity of their liver dysfunction before EIS. Also, delta TB seems to reflect the prognosis of the patients treated by EIS for some extent, since the survival period of the cases treated by EIS were correlative with delta TB (r = -0.734, p < 0.01), and delta TB of 20 cases who survived for longer than 5 years after EIS was 0.04 +/- 0.32. Therefore, delta TB seems to be a useful marker for estimating the influence of EIS on liver function.

Adult↗
PubMed1994

[A case of Rubinstein-Taybi syndrome with bilateral vesicoureteral reflux].

The case was in a 7-month-old boy. Rubinstein-Taybi syndrome was diagnosed from the broad halluces and the characteristic physiognomy noticed since birth. He was brought to us at 7 months of age with fever as the chief complaint. Voiding cystourethrogram showed bilateral vesicoureteral reflux. The testis was palpable in the inguinal canal on either side, but could not be brought to the scrotum. No abnormalities were detected in the penis. From the above findings, he was diagnosed to have bilateral 4th degree vesicoureteral reflux and undescended testes as complicating Rubinstein-Taybi syndrome. The condition was treated by bilateral anti-reflux repair and bilateral orchidopexy at 8 months of age. There has been no recurrence of vesicoureteral reflux for 3 years. A brief discussion was made about the urological complications of Rubinstein-Taybi syndrome.

Cryptorchidism↗
PubMed1994

[Complete eradication by endoscopic injection sclerotherapy reduces the recurrence of esophageal varices].

Endoscopic intravariceal injection sclerotherapy (EIS) using sclerosant mixed with contrast medium was done in 100 patients without hepatocellular carcinoma. They were followed longer than 12 months (mean; 58 +/- 29 months) after EIS. The recurrence rate of esophageal varices in cases with complete eradication (n = 79) and cases with incomplete eradication of (n = 21) was 8.9% and 85.7%, respectively (p < 0.01). In 21 cases, complete eradication was achieved by intravariceal injection and additional therapy using paravariceal injection was not performed. The recurrence rate of this group was only 4.8%. Endoscopic varicealography during injection sclerotherapy were evaluated in 91 cases. At final session of EIS, narrowing of diameter (less than 1 mm) and irregularity of vessel walls were observed in small vessels (devastated vessels). Appearance rate of devastated vessel in 75 cases with completely eradicated esophageal varices was 65.3%. In contrast, among 16 cases with incomplete eradication of varices, devastated vessels were seen only in 6.3% (p < 0.01). It is concluded that the important point in preventing the recurrence of esophageal varices after EIS was the complete eradication of esophageal varices by intravariceal injection sclerotherapy resulting in the eradication of the routes to esophageal varices from port-splenic venous system. For the sake of accomplishment of this treatment, appearance of devastated vessel is very useful.

Adult↗
PubMed1994

Transforming growth factor alpha (TGF alpha) expression in degenerating motoneurons of the murine mutant wobbler: a neuronal signal for astrogliosis?

The enhanced expression of the trophic factor transforming growth factor alpha (TGF alpha) in reactive astrocytes following CNS injury suggests that TGF alpha has a role in the development of astrogliosis. We explored this hypothesis in the murine mutant wobbler, which presents a progressive motoneuronal degeneration associated with an astrogliosis. Evolution of astrogliosis, and expression of TGF alpha precursor (pro-TGF alpha) and of its receptor were examined over the course of the disease, using genetically diagnosed animals and immunocytochemical techniques. We report here that degenerating motoneurons of the cervical spinal cord and a subset of astrocytes express pro-TGF alpha, prior to the onset of astrogliosis, when the first clinical manifestations of the disease are observed at 4 weeks of age. TGF alpha expression appeared strongly correlated with motoneuronal degeneration. All pro-TGF alpha-immunoreactive neurons exhibited a degenerative morphology, and the number of pro-TGF alpha-immunoreactive neurons increased with the progression of the disease. At the glial level, we observed that astrogliosis was a transitory phenomenon in the wobbler mice, developing in coordination with the motoneuronal expression of pro-TGF alpha. Astrogliosis became evident in 6-week-old wobbler mice, when the number of pro-TGF alpha-immunoreactive motoneurons was maximal, and regressed in older mutant mice in correlation with the disappearance of pro-TGF alpha-immunoreactive motoneurons. Furthermore, TGF alpha/EGF receptor immunoreactivity was exclusively localized in a subset of reactive astrocytes, its expression following closely the course of the astrogliosis. These data show that TGF alpha synthesis by the affected motoneurons is an early event in the course of the wobbler disease, and suggest a role for TGF alpha as a neuronal inducer of astrocytic reactivity.

Animals↗
PubMed1994

[Deterioration of liver function following endoscopic injection sclerotherapy of esophageal varices--significance of the new liver function test "intravariceal injection (I.I.) index"].

Changes of liver functions associated with endoscopic injection sclerotherapy (EIS) were investigated in 143 patients with remarkable esophageal varices. The index used for evaluating hepatic reserve was the ratio between the increase of total bilirubin and the increase of LDH after EIS [I.I. index = (delta T.Bil./delta LDH) x 100] in cases treated by intravariceal injection of 5% ethanolamine oleate. I.I. index value caused by hemolysis was stable and always below 0.2, while the elevation of I.I. index above 0.2 was regarded as the reflection of the deterioration of liver function. After the entire sessions of EIS, the changes of liver function tests before and after EIS were estimated in 104 cases using 3 factors as follows; (1) delta T.Bil.; increase of total bilirubin more than 0.5 mg/dl (2) delta PT; decrease of prothrombin time more than 5% (3) delta ICG R15; increase of ICG R15 more than 5%. I.I. index of group I (without any changes of 3 factors mentioned above; n = 66) was 0.22 +/- 0.16, approximately within normal range. However, in group II (with 1 factor; n = 29), group III (with 2 factors; n = 5), group IV (with all factors; n = 4), I.I. index was elevated according to the severity of their liver dysfunction. The cases whose I.I. index value increased gradually during the course of EIS, were apt to deteriorate the liver functions and therefore, should be carefully observed. Also, I.I. index seems to reflect the prognosis of the patients treated by EIS for some extent, since the survival period of the cases treated by EIS were correlative with the value of I.I. index (r = -0.542, p < 0.01), and I.I. index of 32 cases who survived for longer than 5 years after EIS was almost normal (0.22 +/- 0.15).

Adult↗
PubMed1993

5-HT3 receptor antagonists. 3. Quinoline derivatives which may be effective in the therapy of irritable bowel syndrome.

A series of quinolinecarboxylic acid derivatives has been previously described as a new class of 5-HT3 receptor antagonists due to deviation of a carbonyl moiety from the place of an aromatic ring in their minimum-energy conformations. These derivatives were evaluated in a wrap-restraint stress-induced defecation model in rats. Reference compounds, ondansetron (1), granisetron (2), and YM060 (4), potently inhibited a stress-induced increase in stools excreted from fed rats (ID50 = 0.27, 0.12, and 0.0052 mg/kg, po, respectively). However, quinoline derivatives exhibited different activities depending on structural class. 4-Hydroxyquinoline-3-carboxylic acid derivatives 5 and 6a possess high affinity for the 5-HT3 receptor (Ki = 6.1 and 1.5 nM, respectively) and exhibit potent activity in the Bezold-Jarisch (B-J) reflex test (ED50 = 0.0017 and 0.000 10 mg/kg, i.v., respectively), but they did not effectively inhibit the increase in fecal pellet output at the dose of 1 mg/kg, po. On the other hand, most of 1-substituted 2-oxoquinoline-4-carboxylates 10 showed less potent activity in the B-J reflex test than 1 or 2 but inhibited restraint stress-induced defecation more potently than 1 or 2. The ID50 value of endo-8-methyl-8- azabicyclo[3.2.1]oct-3-yl 1-isobutyl-2-oxo-1,2-dihydro-4- quinolinecarboxylate 10e was 0.013 mg/kg, po. With respect to the selected compounds 6a and 10e, effects of 5-HT- and thyrotropin-releasing hormone (TRH)-induced defecation, castor oil-induced diarrhea and wrap-restraint stress-induced colonic propulsion in rats were examined. These 5-HT3 receptor antagonists did not effectively inhibit castor oil-induced diarrhea, which has been reported not to be mediated via the 5-HT3 receptor. Although 10e showed 800-fold decreased potency compared with 4 in the B-J reflex test, 10e exhibited activity as potent as 4 in 5-HT- and TRH-induced defecation assays; 10e exhibited 7-fold increased potency compared with 4 in wrap-restraint stress-induced colonic propulsions. From these results, 10e appears to interact selectively with 5-HT3 receptors in the gastrointestinal system and might be effective in the therapy of irritable bowel syndrome (IBS).

Animals↗