Biomedical subjects

S Sugano

Publications and source records attributed to S Sugano.

At least 109 records · Page 6Linked to original sources

PubMed1998

Expression of transforming growth factor-beta1 and transforming growth factor-beta Type-II receptor mRNA in papillary thyroid carcinoma.

Transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of epithelial cell proliferation. Signal transduction by TGF-beta1 involves direct binding to the TGF-beta Type-II receptor and then the formation of a heterodimeric complex of TGF-beta Type-I and Type-II receptor. To explore the role of TGF-beta1 in thyroid carcinoma, we examined the expression of TGF-beta1 and TGF-beta Type-II receptor mRNA by northern blotting analysis in both 14 papillary thyroid carcinomas and surrounding normal thyroid tissues. Relative mRNA level was determined by scanning densitometry of the autoradiogram and corrected for loading differences using a human beta-actin cDNA probe. The relative mRNA levels of TGF-beta1 in 12 out of 14 papillary thyroid carcinomas were higher than those in surrounding normal thyroid tissues. In contrast, the relative mRNA levels of TGF-beta Type-II receptor were reduced to 60.1+/-18.3% of those of normal thyroid tissues in 10 papillary thyroid carcinomas. There were no clear relationships between the relative mRNA levels for TGF-beta1 and TGF-beta Type-II receptor and the histological characteristics of papillary thyroid carcinomas. The relative mRNA levels for TGF-beta1 and TGF-beta Type-II receptor did not show significant differences in thyroid carcinomas with or without lymph node metastases. There was a negative correlation between the TGF-beta Type-II receptor mRNA level and tumor size, while no significant correlation was observed between the TGF-beta1 mRNA level and tumor size. In conclusion, most papillary thyroid carcinomas overexpress TGF-beta1 mRNA but exhibit a reduction in TGF-beta Type-II receptor mRNA. The reduction of TGF-beta Type-II receptor mRNA may play a role in the pathogenesis of papillary thyroid carcinoma.

Adult↗

PubMed1998

Retinal complications and plasma C5a levels during interferon alpha therapy for chronic hepatitis C.

OBJECTIVE: The pathogenesis of retinal complications, such as retinal hemorrhage and cotton-wool spots formation, during interferon (IFN) therapy is unclear. We studied the relationship between the presence of retinal complications and levels of plasma-activated complement 5 (C5a), a known potent intravascular aggregator of granulocytes, during IFN-alpha therapy. METHODS: Forty-five patients with chronic hepatitis C but without diabetes mellitus and hypertension were studied. IFN-alpha was used 10 MU per day for 2 wk and 3 times weekly for an additional 22 wk. In 25 patients with IFN therapy, the optic fundi were examined before therapy began, every 4 wk thereafter, and whenever patients complained of visual symptoms. C5a levels were measured before, and during the 4th, 8th, 12th, and 24th wk, and at any time that a retinal complication was discovered. Twenty patients served as IFN-untreated controls. They had six optic fundi examinations, each 4 wk apart. C5a levels were measured three times, 4 wk apart, in 10 controls. RESULTS: No retinal hemorrhage or cotton-wool spots were detected before IFN-alpha therapy or in any of the controls. However, retinal hemorrhage occurred in six patients (24%) during IFN-alpha therapy. Five of six episodes occurred within the first 8 wk. Only three patients with retinal hemorrhage had visual symptoms. Cotton-wool spots developed in four patients with retinal hemorrhage. Retinal hemorrhage and cotton-wool spots resolved gradually despite continuous administration of IFN-alpha. Before IFN therapy and in controls, all C5a levels were <7 ng/ml. When retinal hemorrhage occurred, C5a was significantly increased (27.3+/-15.6 ng/ml,p < 0.01) relative to levels from the same patients before and after the hemorrhage (5.7+/-1.1 ng/ml), and also relative to levels in IFN-a-treated patients without retinal hemorrhage (5.7+/-1.1 ng/ml) and compared with levels in IFN-untreated controls (5.4+/-0.7 ng/ml). CONCLUSIONS: Retinal hemorrhage or cotton-wool spots often occur during IFN-alpha therapy for chronic hepatitis C. This study suggests that a high C5a level may be an important step in the pathogenesis of retinal capillary infarction, hemorrhage, and cotton-wool spots formation.

Adult↗

PubMed1998

Establishment of a 24-hour electrocardiogram recording system using a Holter recorder for miniature swine.

A Holter recording system was established for the Göttingen miniature swine. For this purpose, we first developed a jacket to hold a Holter recording set, and subsequently determined a bipolar lead suitable for obtaining stable electrocardiogram (ECG) recording without artifacts. To make the jacket, we measured the lengths of eight sites of the body of 14 miniature swine. Several types of jackets were made and tested. We observed the behaviour of animals with these jackets by videotape recorder (VTR) recording. These observations permitted development of a jacket suitable for Holter recording. The jacket permits easy placement of the recorder, and long-term ECG recording can be performed without difficulty. In order to determine a suitable lead for long-term recording, we recorded ECGs from six adult miniature swine using three types of leads, the M-X, R-L and A-B leads. The R-L lead frequently exhibited baseline drift, and QRS complexes often disappeared in this lead due to low amplitude. ECG recording with the M-X and A-B leads was of sufficient quality to permit analysis. This system is expected to be useful for further cardiovascular research in miniature swine.

Anesthesia↗

PubMed1998

Power spectral analysis of heart rate variability in a horse with atrial fibrillation.

This study has demonstrated the power spectral analysis of heart rate variability in a horse with atrial fibrillation. A large peak in the high frequency (HF) area of the power spectrum appeared in the horse. Hourly heart rate, the low frequency (LF) power, the HF power, and LF/HF ratio were almost constant during the recording period. The values of HF and LF power in the horse with atrial fibrillation were much larger than those in normal horses. The normalized unit of HF (HF n.u.) was much larger than that of LF (LF n.u.). Furthermore, the LF/HF ratio was very small in the horse. These results suggest that the ventricular rhythm has a respiratory related periodicity in the horse with atrial fibrillation and the predominant parasympathetic activity may modulate the intrinsic behavior of the atrioventricular node during atrial fibrillation.

Animals↗

PubMed1998

Airway responsiveness to acetylcholine in congenitally bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs in vivo and in vitro.

The characteristics of airway responsiveness to acetylcholine (ACh) in congenitally bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs were clarified in vivo and in vitro. We measured the change in ventilatory mechanics in response to ACh inhalation by means of the bodyplethysmograph and the contractile responses of isolated trachea to ACh and carbachol (CCh). Further, muscarinic receptor subtypes involved these responses were identified. The basal values for ventilatory mechanics in BHS were not significantly different from those in BHR. Respiratory resistance to ACh was progressively increased in a time- and dose-dependent manner in BHS. The contractile responses of tracheal smooth muscle to ACh in BHS were significantly greater than those in BHR, but CCh-induced responses in BHS and BHR were similar. ACh- and CCh-induced contractions were mediated via M3 receptors. These results suggested that the falling-down of BHS in response to ACh inhalation was caused by the strong constriction of the airway and the reduction in ventilation. Moreover, the airway hyperresponsiveness to ACh in BHS might be partly dependent on the change in acetylcholinesterase activity.

Acetylcholine↗

PubMed1998

Histamine-induced airway contraction in congenitally bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs.

Airway hyper-responsiveness is known as an important pathogenesis of asthma. In the present study, the airway responsiveness to aerosolized and injected histamine in congenitally bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs was investigated. In addition, the role of the vagal reflex in histamine-induced airway contraction was evaluated by vagal blocking with atropine inhalation or bilateral vagotomy. A significantly higher bronchoconstrictive reaction, i.e., a decrease in tidal volume (VT) and an increase in respiratory resistance (Rrs), to histamine-inhalation was observed in BHS than in BHR. A noticeably lower reduction in VT was noted after atropine pretreatment for both BHS and BHR, whereas an increase in Rrs was inhibited only in BHS. The intravenous injection of histamine caused a noticeable bronchoconstrictive reaction in both BHS and BHR with a dose-dependent relationship, but no significant differences were observed and the bilateral vagotomy failed to induce any difference between the two animal groups. These results demonstrated that the airway responsiveness to histamine is considerably different in BHS from that in BHR, but the difference is largely dependent on the route of administration of histamine. The important role of the vagal reflex on the elicitation of airway contraction was elucidated in both animal groups, and it appeared that the BHS possessed relatively higher dependency on the vagal reflex mechanism than the BHR.

Administration, Inhalation↗

PubMed1997

Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.

Using 'oligo-capped' mRNA [Maruyama, K., Sugano, S., 1994. Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 138, 171-174], whose cap structure was replaced by a synthetic oligonucleotide, we constructed two types of cDNA library. One is a 'full length-enriched cDNA library' which has a high content of full-length cDNA clones and the other is a '5'-end-enriched cDNA library', which has a high content of cDNA clones with their mRNA start sites. The 5'-end-enriched library was constructed especially for isolating the mRNA start sites of long mRNAs. In order to characterize these libraries, we performed one-pass sequencing of randomly selected cDNA clones from both libraries (84 clones for the full length-enriched cDNA library and 159 clones for the 5'-end-enriched cDNA library). The cDNA clones of the polypeptide chain elongation factor 1 alpha were most frequently (nine clones) isolated, and more than 80% of them (eight clones) contained the mRNA start site of the gene. Furthermore, about 80% of the cDNA clones of both libraries whose sequence matched with known genes had the known 5' ends or sequences upstream of the known 5' ends (28 out of 35 for the full length-enriched library and 51 out of 62 for the 5'-end-enriched library). The longest full-length clone of the full length-enriched cDNA library was about 3300 bp (among 28 clones). In contrast, seven clones (out of the 51 clones with the mRNA start sites) from the 5'-end-enriched cDNA library came from mRNAs whose length is more than 3500 bp. These cDNA libraries may be useful for generating 5' ESTs with the information of the mRNA start sites that are now scarce in the EST database.

Animals↗

PubMed1997

Cloning and characterization of mouse Dhm2 cDNA, a functional homolog of budding yeast SEP1.

We have isolated mouse Dhm2 cDNAs encoding a homolog of budding yeast SEP1, whose product is involved in many cellular processes including meiosis, cellular senescence, and telomere maintenance. The putative Dhm2 protein (Dhm2p), which consists of 1687 amino acids and whose molecular weight is 191,400, matches the size of Sep1p and shares extensive homology with Sep1p especially in their N-terminal regions. A multicopy plasmid containing of the Dhm2 cDNA complements the slow growth phenotype, sporulation defect, and DNA recombination defect caused by the sep1 mutation in yeast, indicating that Dhm2 is a functional homolog of SEP1. Since Dhm1, another SEP1 homolog we reported previously, only partially compensates for the sep1 mutation, we conclude that Dhm2 is a true homolog of SEP1. Northern analysis revealed that 5.8 kb mRNA corresponding to Dhm2 open reading frame is produced highly in testis. These results strongly suggest that Dhm2p participates in gametogenesis in mouse.

Animals↗

PubMed1997

Cloning of the promoter regions of mouse TGF-beta receptor genes by inverse PCR with highly overlapped primers.

In order to isolate promoters of mouse TGF-beta receptor genes, we used inverse PCR with highly overlapped primers corresponding to the 5' sequence of the receptor cDNAs. Nested primer sets only covered a 30- to 40-base region of the sequences. HinfI-digested and self-ligated mouse genomic DNA was used as a PCR template. Only one band for each receptor was seen after PCR. The amplified DNA fragments could direct luciferase production when the luciferase coding sequence was ligated after the fragments. The sequence of the fragment which correspond to the type II receptor showed partial homology with the promoter region of the human TGF-beta type II receptor. Thus, the inverse PCR with highly overlapped primers could be an easy way to isolate the promoter regions of many genes.

Animals↗

PubMed1997

Genomic structure and promoter analysis of the gene encoding MM3, a member of transmembrane 4 superfamily.

We have isolated genomic clones encoding hamster MM3, a member of transmembrane 4 superfamily (TM4SF). Nucleotide (nt) sequence analysis revealed that it is composed of 5 exons spanning about 8 kb. The exon-intron organization of the MM3 gene was quite different from those of other TM4SF members. We also identified its transcription start points (tsp) and the promoter region. Deletion analysis of the promoter revealed that about 160-bp region containing TATA-box, CAAT-box and GC-box was necessary for efficient transcription in cultured cells.

Amino Acid Sequence↗

PubMed1997

Hepatic actinomycosis: case report and review of the literature in Japan.

Hepatic actinomycosis is rare. We report an 86-year-old Japanese man with a 3-day history of high fever and anorexia who had an actinomycotic liver abscess complicated by disseminated intravascular coagulation (DIC). A definitive diagnosis was made when an Actinomyces species was cultured from aspirated pus. The clinical course was satisfactory. Treatment included prompt percutaneous drainage coupled with long-term intravenous administration of high-dose minocycline and piperacillin, combined with therapy for DIC. We reviewed 11 cases in Japan of Actinomyces involving the liver, including the case reported here. In most patients, there were no predisposing factors. Common symptoms and laboratory findings included fever, abdominal pain, leukocytosis, and elevated C-reactive protein. In 6 of the 11 patients a partial hepatectomy was performed because hepatic tumor was suspected. Five patients presented with a liver abscess. Hepatic actinomycosis should be considered in the differential diagnoses of pyogenic liver abscess and space-occupying lesions of the liver.

Actinomyces↗

PubMed1997

Human cytomegalovirus open reading frame UL11 encodes a highly polymorphic protein expressed on the infected cell surface.

Human cytomegalovirus (HCMV) open reading frame (ORF) UL11 locates within a polymorphic region of the viral genome identified previously by a restriction-fragment-length-polymorphism. We report here that ORF UL11 encodes a polymorphic protein expressed on the surface of HCMV-infected cells. First, we determined the nucleotide sequence of ORF UL11 from ten strains and compared it among the strains. Out of 205 amino acids consisting of the predicted N-terminal region beside the putative transmembrane stretch in strain AD169, 88 residues were divergent on more than one strain. In contrast, the predicted C-terminal side including the putative transmembrane domain was identical at the amino acid sequence level. In addition, the number and location of predicted cysteine residues were also conserved. Next, we screened a cDNA library from HCMV-infected cells and obtained a cDNA clone containing the full-length ORF UL11. Finally, we identified the gene product of UL11 on the surface of HCMV-infected cells by FACS analysis with polyclonal antibodies generated against a glutathione S-transferase/UL11 fusion protein. The fusion protein contained a region within the N-terminal side next to the predicted transmembrane stretch. These results indicate that the N-terminal side of UL11 protein containing variable amino acid residues protrudes from the infected cell surface.

Amino Acid Sequence↗

PubMed1997

Chronic splanchnic hemodynamic effects of low-dose transdermal nitroglycerin versus low-dose transdermal nitroglycerin plus spironolactone in patients with cirrhosis.

We studied the hemodynamic changes following a four-week administration of either low-dose transdermal nitroglycerin (a constant release of 5 mg of nitroglycerin/day) (N = 10) or low-dose transdermal nitroglycerin plus spironolactone (100 mg/day) (N = 9) in patients with cirrhosis and portal hypertension. Two patients in the latter group did not undergo repeat measurements after dropping out because of severe headaches or developing ascites during the study. Transdermal nitroglycerin induced a significant reduction in the hepatic venous pressure gradient (HVPG) (-11.7 +/- 14.9%, P < 0.05), which was associated with a significant reduction of cardiac output (-10.5 +/- 7.3%). Nitroglycerin plus spironolactone induced a significant reduction in the HVPG (-18.3 +/- 16.0%, P < 0.05) associated with a significant reduction of cardiac output (-13.8 +/- 5.6%), right atrial pressure (-35.0 +/- 30.0%), mean arterial pressure (-7.5 +/- 6.8%), and plasma volume (-10.2 +/- 7.0%). The difference of the mean HVPG reduction between the groups was insignificant. A decrease in the HVPG greater than 10% was observed in six of 10 patients (60%) and in five of seven patients (71.4%), defined as "responders," at four weeks. The difference in percentage of responders between the groups was insignificant. We found that in some cirrhotic patients, low-dose transdermal nitroglycerin is potentially useful in the treatment of portal hypertension. Spironolactone as an adjunct to low dose transdermal nitroglycerin did not demonstrate therapeutic advantages in the treatment of portal hypertension in cirrhotics. That there were nonresponders indicates that there are variable responses in splanchnic hemodynamics to these drugs.

Administration, Cutaneous↗

PubMed1997

Transplantable rat thyroid cancer cell line FRTC transformed with muramyl dipeptide.

A rat thyroid cancer cell line, FRTC, was established from the normal rat thyroid cell line, FRTL-5. FRTL-5 cells were cultured in vitro with N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) for 4 days and were transplanted intraperitoneally into Fisher rats. Disseminated tumour formation in the peritoneum was found in ten out of ten rats in which MDP-treated FRTL-5 cells were transplanted. Colloid-like structures stained with anti-thyroglobulin (Tg) antibodies were observed in the tumours. On the other hand, no tumour was found in any of the rats in which untreated FRTL-5 cells were transplanted. No morphological changes were observed in FRTL-5 cells after long-term in vitro culture in the presence of MDP. MDP had no effect on thymidine incorporation, the production of cAMP or the expression of c-myc in FRTL-5 cells in vitro. Cells from the tumour (FRTC) secreted Tg in vitro and expressed Tg, thyroid peroxidase (TPO) and thyrotropin (TSH) receptor mRNA. The expression of TSH receptor mRNA increased in FRTC cells after TSH stimulation. FRTC cells produced cAMP in response to TSH stimulation in a dose-dependent manner. However, the growth of FRTC cells was TSH independent. Expression of c-myc and c-fos was observed in FRTC cells in vivo as well as in vitro. FRTC cells formed tumours in Fisher rats when transplanted subcutaneously. FRTC cells have several characteristics of differentiated thyroid cancer cells and may provide a good model for the study of human differentiated thyroid cancers.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1997

Selective production of transgenic mice using green fluorescent protein as a marker.

The low efficiency of transgenic animal production by microinjection has been a serious problem especially for the production of transgenic livestock. We developed a method to selectively produce transgenic mice using green fluorescent protein (GFP) as a marker. Using this method, we obtained eight fetuses and four live-born mice derived from 55 GFP-positive blastocysts. PCR analysis showed 11 out of 12 mice (fetuses and newborn mice) were transgenic. Southern blot analysis showed that 8 out of 12 were transgenic. GFP expression was also observed in bovine blastocysts, suggesting that this method should contribute to the efficient production of transgenic livestock.

Animals↗

PubMed1997

Fiber composition of the superior laryngeal nerve in rats and guinea pigs.

The fiber composition of the superior laryngeal nerve (SLN) which is served as the laryngeal afferent pathway was clarified in rats and guinea pigs. The proportions of the number of myelinated and unmyelinated fibers in the SLN were almost the same in both rats and guinea pigs. The unmyelinated fibers show the peak distribution of axon diameter ranging from 0.79 to 1.00 micron in both species, whereas the peak distribution of myelinated fibers ranged from 2.51 to 3.16 microns in rats and from 3.98 to 5.01 microns in guinea pigs. The mean axon diameter of unmyelinated fibers was significantly larger in rats (mean: 1.12 microns) than in guinea pigs (0.96 micron), whereas that of myelinated fibers was significantly larger in guinea pigs (4.04 microns) than in rats (3.30 microns). Such findings would reflect the cardiopulmonary reflexes elicited from the larynx in these animal species.

Afferent Pathways↗

PubMed1997

Bradykinin-induced airway contraction in two lines of guinea pigs with congenitally different airway sensitivity.

The airway responsiveness to bradykinin (0.1, 1 and 10 microg/kg, i.v.) was examined in two lines of guinea pigs, BHS (bronchial hypersensitive) and BHR (bronchial hyposensitive) lines, with different airway sensitivity to inhalation of acetylcholine (ACh)-aerosol. Normal Hartley strain guinea pigs were used as a control group. The airway contraction was measured by recording intratracheal pressure (P[IT]) and respiratory airflow (V) under the condition of artificial ventilation in anesthetized guinea pigs. The results show airway responsiveness to bradykinin in BHS guinea pigs to be significantly greater than in BHR and normal Hartley strain guinea pigs.

Airway Resistance↗

PubMed1997

The afferent activity of the superior laryngeal nerve, and respiratory reflexes specifically responding to intralaryngeal pressure changes in anesthetized Shiba goats.

This study was aimed at characterizing the superior laryngeal nerve (SLN) afferent activities under four different respiratory conditions, i.e., tracheostomy breathing (TB), upper airway breathing (UAB), tracheal occlusion (TO) and upper airway occlusion (UAO), and investigating respiratory changes in response to transmural pressures applied to the larynx in anesthetized Shiba goats. The activity recorded from the whole SLN increased at both inspiration and expiration during TB, UAB and TO, while an expiratory augmentation accompanied by an inspiratory inhibition was found during UAO. Based on recordings from 109 thin filament-preparations, 47 units were identified as 'drive' receptors, 31 as 'pressure' receptors (22 'positive' and 9 'negative' pressure receptors), and the rest 31 as 'non-modulated type' of receptors. The posterior cricoarytenoid (PCA) muscle activity showed a clear inspiratory modulation during UAB and was significantly enhanced by negative pressure applied to the isolated upper airway, where such an augmented activity was abolished by bilateral section of the SLN. No significant changes were found in the respiratory cycle during application of negative pressures to the larynx. The respiratory modulation of the SLN in Shiba goats was essentially identical to that reported for rabbits, rats and guinea pigs, but not in dogs. The reflex response of the upper airway muscles to the laryngeal pressure changes in Shiba goats were found to be less noticeable than in rabbits and dogs.

Airway Obstruction↗