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Biomedical subjects

R Suzuki

Publications and source records attributed to R Suzuki.

At least 19 recordsLinked to original sources

Role of colony-stimulating factor-1 in macrophage activation in tumor-bearing mice.

We previously reported a dramatically increased number of macrophages in tumor-bearing mice. In this study, we investigated the involvement of CSF in that phenomenon. CSF-1 responding cells as macrophages precursors increased significantly in number in the spleens of tumor-bearing mice as compared with those in normal mice. Splenic cells and sera from the tumor-bearing mice respectively expressed CSF-1 in mRNA and serum protein levels, but failed to express the other CSF (granulocyte-macrophage-CSF or IL-3). Nonadherent splenic mononuclear cells (< 0.5% macrophages) from normal mice proliferated and differentiated into mature macrophages in culture within 7 days with recombinant mouse CSF-1 (rCSF-1). Both macrophages harvested from tumor-bearing mice and those activated in vitro with rCSF-1 expressed mostly Mac-1, -2 (and -3) Ag, showed yeast phagocytosis, produced IL-1 but not IL-2 or IL-3, and displayed potent cytotoxicity against NK cell resistant Meth-A tumor cells. These macrophages also expressed lipocortin I mRNA and secreted lipocortin I protein, and suppressed mitogenic responses of splenic lymphocytes. rCSF-1-activated macrophages derived from nonadherent splenic cells expressed both CSF-1 and CSF-1 receptor (c-fms) mRNA. Administration of rCSF-1 into normal mice induced hemopoietic and immunologic alternations similar to those observed in tumor-bearing mice. These results suggest that CSF-1 is involved in the dramatic increase of macrophages in tumor-bearing mice, possibly through an autocrine or paracrine loop.

Animals

Gamma/delta T cell antigen receptors expressed on tumor-infiltrating lymphocytes from patients with solid tumors.

The expression of gamma/delta T cell antigen receptors (TcR) in T cell lines or clones derived from tumor-infiltrating lymphocytes (TIL) from patients with solid tumors was investigated. gamma/delta TcR T cell lines were derived from TIL from patients with Wilms tumor, sarcoma or metastatic melanoma by stimulation with autologous tumor cells alone and recombinant interleukin 2 and they exhibited nonspecific cytotoxicity against autologous and allogeneic tumor cells, or cells of the K562 or the MEL21 tumor cell lines. Two T cell lines were derived from a patient with Wilms tumor. One of them expressed a non-disulfide-linked gamma/delta TcR using the 60-kDa gamma chain, whereas, the other expressed a disulfide-linked gamma/delta TcR. A T cell line was derived from a patient with sarcoma and expressed a disulfide-linked gamma/delta TcR, whereas, a T cell line derived from a patient with melanoma expressed a non-disulfide-linked gamma chain of 62 kDa. Several T cell clones were developed from patients with metastatic melanoma or Wilms tumor and expressed either disulfide- or non-disulfide-linked gamma/delta TcR. Northern analysis of RNA from certain of these clones revealed a full-length gamma chain transcript, whereas, the alpha or beta chain transcripts were either absent or truncated. These T cell clones exhibited nonspecific cytotoxicity. Both disulfide- and non-disulfide-linked TIL T cell lines and clones expressed the delta TCS1 determinant. gamma/delta TcR+ cells in freshly prepared TIL from these patients were present in low proportions (less than 5%) and their delta TCS1/delta 1 ratios were within the range observed in the peripheral blood of normal donors. These results demonstrate that both disulfide- and non-disulfide-linked gamma/delta TcR are expressed on T cell lines and clones derived from TIL from solid tumors. Non-disulfide-linked gamma/delta TcR using the 56-66-kDa gamma chain are frequently found on TIL-derived T cell lines and clones. These 56-66-kDa gamma chains are rarely expressed on T cell lines or clones derived from peripheral blood lymphocytes of normal donors.

Cell Line

Postcataract against-the-rule astigmatism after phacoemulsification procedure. Characteristic changes over time.

To further determine whether postoperative astigmatism is related to the amount of preoperative astigmatism, we analyzed two types of against-the-rule (AR) astigmatism induced by phacoemulsification and aspiration (PEA) procedures. The operations all utilized 10-0 polyester (Mersilene) in double running fashion for the closure of the corneoscleral incisions. The induction and spontaneous regression of several types of astigmatism were analyzed over 6 months. Surgery was all done by one surgeon, with the same surgical procedure and the same number of sutures. In postoperative AR astigmatism less than 0.7 D at 6 months, although the amount of the astigmatism 1 week postoperatively was remarkably increased (2.66 +/- 0.17 D), postoperative astigmatism was decreased 6 months following surgery. On the other hand, in postoperative AR astigmatism greater than 1.5 D at 6 months, the power of the astigmatism 1 week postoperatively (2.12 +/- 0.13 D) was not much higher than the preoperative level (1.38 +/- 0.08 D), but tended to continue increasing even 6 months after surgery. There was no difference in the power of astigmatism between 1 and 3 months postoperatively. The eyes with preoperative astigmatism (e.g. 1.38 +/- 0.08 D) and especially preoperative AR astigmatism (e.g. 1.60 +/- 0.11 D), showed an increase of their astigmatism after the PEA procedure. We discussed some risk factors which may induce greater postoperative AR astigmatism.

Astigmatism

Unusual rapidly growing gastric myxoid neurofibroma: a case report.

A 62-year-old man was first found to have a gastric tumor in the fornix during a routine health examination 16 months previously. The case was not associated with von Recklinghausen's disease. Initially, the tumor was approximately 4 mm in diameter, but grew very rapidly to 20 mm in 13 months, and to 30 mm in the following month, without manifesting clinical symptoms. Malignancy was suspected because of the rapid growth and the endoscopic findings: a rough-granular elevated lesion with a wide stalk, and with erosions and mucus on its surface. Although endoscopic biopsy was done several times, the routine histological examinations were inconclusive. Endoscopic resection was therefore carried out. Examination of the resected specimen showed that the main elements consisted of wavy, long-spindled cells, which crossed irregularly, and whose interstitium was myxomatous. Immunohistochemically the specimen showed strongly positive reaction for S-100 protein and positive reaction for neuron specific enolase (NSE). Based on these immunohistochemical findings, a final diagnosis of gastric myxoid neurofibroma was made, which showed rapid growth due to myxomatous change. The patient showed a good postoperative course and no recurrence has been recognized by follow-up endoscopy.

Humans

Peritumoral cerebral edema in meningiomas: the role of the tumor-brain interface.

We investigated the role of the tumor-brain interface in the production of peritumoral cerebral edema in meningiomas by analysing the size, shape, histological type and location of the tumor, and radiological and operative findings. Our results suggest that changes of the boundary zone between the tumor and the brain such as the disappearance of the subarachnoid space, cortical thinning or loss, and possibly partial loss of the arachnoid membrane are the most important factors in edema production, and that multiple other factors determine the morphological changes which occur at the tumor-brain interface.

Adult

Involvement of prejunctional alpha 2-adrenoceptor in bovine ciliary muscle movement.

The effects of adrenergic agents on bovine ciliary muscle were studied in vitro. Norepinephrine, phenylephrine, or isoproterenol did not affect the muscle tone. High concentrations of guanethidine (10(-5) M) partly inhibited the nerve-mediated contractions of the muscle. The nerve-mediated contractions also were inhibited in the following order: norepinephrine > epinephrine >> isoproterenol. The inhibition was blocked by yohimbine or phentolamine, but not by optimum concentrations of prazosin, moxisylyte, propranolol, and carteolol. Usual concentrations of phosphodiesterase inhibitors markedly inhibited the nerve-mediated and carbachol-induced contractions. These results suggest that an adrenergic alpha 2 receptor located at the nerve terminals inhibits the contraction of cholinergically innervated ciliary muscle. Adrenergic innervation seems to play an inhibitory role in the muscle tissue when the muscle tone is elevated.

Animals

Effect of phosphodiesterase inhibitors on bovine ciliary muscle and outflow facility.

To understand the aqueous outflow mechanism, we compared changes in the outflow facility with the response of ciliary muscle in fresh bovine eyes. The facility was measured in intact ocular globes. Theophylline, caffeine, and isobutylmethylxanthine (IBMX), all phosphodiesterase (PDE) inhibitors, increased outflow facility in a dose-dependent manner. However, neither epinephrine nor isoproterenol increased the outflow facility, regardless of their concentrations up to 10(-3) M. Neither epinephrine nor isoproterenol (0.01-1 microM)) relaxed the tone of bovine ciliary muscle, whereas theophylline and IBMX remarkably relaxed the muscle which had been contracted by carbachol, and also inhibited the nerve-mediated contraction. It is interesting that PDE inhibitors have a much greater influence on changes in outflow facility and ciliary muscle contraction than beta-adrenergic agonists.

1-Methyl-3-isobutylxanthine

Expression of the amino-terminal half of the NS1 region of the hepatitis C virus genome and detection of an antibody to the expressed protein in patients with liver diseases.

A cDNA fragment encompassing the 5'-terminal half of the NS1 region of the hepatitis C virus (HCV) genome was cloned. The cDNA was expressed in insect cells using a recombinant baculovirus, and a protein band of approximately 21K was identified by immunoblotting with a serum sample from a patient with chronic hepatitis C. Antibody to the protein was detected in sera from 13.4% of patients with chronic non-A, non-B hepatitis (NANBH), 20.8% of patients with liver cirrhosis and 16.8% of patients with hepatocellular carcinoma with no serum markers for hepatitis B virus infection. However, the antibody was not detected in sera from patients with acute NANBH. The prevalence of antibody to the protein encoded by the NS1 region was lower than that of antibody to the HCV core protein, but much higher than that of antibody to the envelope protein. Thus, the NS1 region of the HCV genome is suggested to encode a protein produced during the course of HCV replication.

Animals

Effects of long-term oral administration of amiodarone on the electromechanical performance of rabbit ventricular muscle.

1. The effects of long-term administration of oral amiodarone on transmembrane action potential and contraction of ventricular muscle were investigated in rabbits. 2. ECGs of rabbits that received oral amiodarone 50 mg or 100 mg kg-1 daily for 4 weeks, showed a significant prolongation of RR, QT and corrected QT (QTc) intervals, whereas PQ and QRS were unaffected. Serum and myocardial tissue amiodarone concentrations were 0.14-0.18 micrograms ml-1 and 1.47-3.63 micrograms g-1 wet wt. respectively. 3. Right ventricular papillary muscles isolated from treated rabbits were characterized by a moderate prolongation of action potential duration (APD) compared with controls. A slight decrease of the maximum upstroke velocity (Vmax) was also observed at the higher dose. The APD prolongation by chronic amiodarone, unlike acute effects of sotalol, E-4031, Cs+ and 4-aminopyridine, did not show marked reverse use-dependence. 4. APD and Vmax restitution following slow basic stimuli (0.03 Hz) were unaffected by chronic treatment with amiodarone. 5. Acute application of amiodarone (10 microM) caused a significant decrease in APD and developed tension, as well as a marked use-dependent Vmax inhibition with fast recovery kinetics. 6. These findings suggest that a major and consistent electro-physiological effect of chronic amiodarone is repolarization delay (Class-III action) showing minimal frequency-dependence. However, when amiodarone above a certain concentration is present in the extracellular space, a fast kinetic Class-I action would be added as an acute effect.

Action Potentials

Electrophysiological effects of diprafenone, a dimethyl congener of propafenone on guinea-pig ventricular cells.

1. The effects of diprafenone and propafenone on transmembrane action potential were examined and compared in papillary muscles and single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, both diprafenone and propafenone > or = 10(-6) M caused a significant and dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential. 3. In the presence of either drug, trains of stimuli at rates > or = 0.1 Hz led to an exponential decline in Vmax. A time constant (tau R) for Vmax recovery from the use-dependent block was 15.5 s for diprafenone and 8.8 s for propafenone. 4. The use-dependent block of Vmax with diprafenone was enhanced when the resting potential was depolarized by high (8, 10 mM) [K+]o, whereas that with propafenone was virtually unchanged. tau R with diprafenone was shortened by the depolarization, while that with propafenone was rather prolonged. 5. In single myocytes perfused with diprafenone or propafenone, 10 ms conditioning clamp to 0 mV caused a significant decrease in Vmax of subsequent action potential. A prolongation of the clamp pulse duration resulted in a modest enhancement of the Vmax inhibition with diprafenone, while a large enhancement of the Vmax inhibition occurred with propafenone. 6. These findings suggest that diprafenone, like propafenone, may block the sodium channel during both the activated and inactivated states. The relative contribution of inactivation block is less important for diprafenone than for propafenone. The different voltage-dependence of use-dependent block with diprafenone from propafenone would contribute to its high antiarrhythmic potency.

Action Potentials

Expression of processed envelope protein of hepatitis C virus in mammalian and insect cells.

The putative envelope protein of hepatitis C virus (HCV) was expressed in insect cells by using a baculovirus expression vector and in monkey COS cells under the control of exogenous promoters. The expressed envelope proteins, identified by immunoblot analysis using sera from patients with chronic HCV infection, were a series of glycoproteins of 35 to 24 kDa (gp35-24) in insect cells and a single species of glycoprotein of 35 kDa (gp35) in monkey cells. The size difference of these proteins was due to the different degrees of glycosylation. The envelope proteins expressed in these cells were produced by common specific cleavage from the precursor protein, and cleavage positions of the envelope protein were mapped at about amino acids 190 and 380. The gp35-24 proteins expressed in insect cells were used for detection of antibody against HCV envelope protein in patient sera. The results showed that (i) the antibody is detected in 2 to 17% of various patients with hepatitis C, (ii) three patients were apparently cured after acquiring the antienvelope antibody, and (iii) in sera of patients with more than a 20-year history of infection, the antibody sometimes coexisted with HCV. These results suggest that the antienvelope antibody is neutralizing only in limited number of patients with hepatitis C.

Animals

Similarities and differences between the Kelman phacoemulsification and extracapsular cataract extraction procedures in the spontaneous regression of corneal astigmatism from against-the-rule astigmatism.

We perspectively examined the induction and spontaneous regression of corneal astigmatism from preoperative against-the-rule astigmatism [Kelman phacoemulsification (KPE), n = 618; extracapsular cataract extraction (ECCE), n = 192] among cataract extraction surgeries (KPE, n = 1,648; ECCE, n = 443). All data were set on a double-angle coordinate graph, from which the mean +/- SE of the axis and the amount of astigmatism were obtained simultaneously. In the KPE group, the surgically induced astigmatism was independent of preoperative state or age. In the ECCE group, surgically induced astigmatism shifted toward with-the-rule astigmatism, and postoperative recovery was delayed longer in patients over 80 years of age than in those under 70. Postoperative against-the-rule astigmatism was more frequent after KPE. Our first trial to calculate astigmatism from a double-angle coordinate graph was useful in showing astigmatism changes.

Aged

Ibudilast may improve retinal circulation in patients with diabetes mellitus.

Ibudilast selectively vasodilates cerebral vessels without reducing blood pressure. We investigated the effect of the drug on retinal circulation in 8 patients with diabetes mellitus, using the video-densitometric image analysis of fluorescein angiography. We compared the build up time, the time constant of washout rate and the mean circulation time (MCT) before and after oral therapy with ibudilast. After 2 weeks of daily administration (30 mg), MCT was shortened significantly (4.2 +/- 2.8 vs. 3.0 +/- 1.6 s, p = 0.0215). Since retinal circulation in patients with diabetes mellitus was improved by ibudilast, the drug may be useful to treat disorders such as diabetic retinopathy.

Administration, Oral

Effect of moxisylyte hydrochloride (alpha 1-blocker) on the retinal circulation of patients with diabetes mellitus.

Moxisylyte hydrochloride (alpha 1-blocker) selectively vasodilates cerebral vessels without reducing blood pressure. We investigated the effect of the drug on retinal circulation in 15 patients (17 eyes) with diabetes mellitus, using the video-densitometric image analysis of fluorescein angiography. We compared the build-up time (BT), the time constant of washout rate (TC) and the mean circulation time (MCT) before and after oral therapy with moxisylyte. In 16 eyes, BT was shortened significantly and MCT was only slightly shortened 1 h after oral therapy with moxisylyte. After 2 weeks of daily administration, MCT was shortened and TC of the artery was increased significantly in 6 eyes. Since retinal circulation in patients with diabetes mellitus was improved by moxisylyte, the drug may be useful to treat ocular disorders such as diabetic retinopathy.

Administration, Oral

Sudden against-the-rule astigmatism 6 months after intraocular lens implantation with the Kelman phacoemulsification procedure: 4 of 809 cases.

Of 809 eyes that underwent the Kelman phacoemulsification and aspiration (KPE) procedure, we report on 4 patients (0.49%) who developed sudden against-the-rule (AR) astigmatism after intraocular lens implantation. These patients had had with-the-rule astigmatism preoperatively to 3 months postoperatively and suddenly developed AR astigmatism 6 months after surgery. To study the development and progression of AR astigmatism in these patients (group A), we compared their 6-month time course with that of 257 patients (group B) with postoperative AR astigmatism. In group A, the degree of astigmatism was not significantly different from group B astigmatism preoperatively (1.03 +/- 0.16 vs. 1.04 +/- 0.04 dptr) and 6 months postoperatively (1.32 +/- 0.13 vs. 1.26 +/- 0.05 dptr). However, 1 week postoperatively, the astigmatism of the 4 cases was much greater (5.72 +/- 0.14 dptr) than that of the others (2.32 +/- 0.07 dptr). These rare 4 cases, which had no other unusual characteristics, are indicative of the importance of a careful follow-up even if the post-KPE course seems uneventful.

Aged

Outcome of preoperative against-the-rule astigmatism after phacoemulsification: characteristic changes over time. Part II.

To determine the outcome of preoperative against-the rule (AR) astigmatism among 1,648 phacoemulsification and aspiration (PEA) procedures, we analyzed the post-cataract time course of astigmatism over 6 months in 618 eyes divided into three groups. In preoperative AR astigmatism less than 0.75 dptr (n = 208), the astigmatism increase 1 week postoperatively was rapid. In preoperative AR astigmatism greater than or equal to 1.5 dptr (n = 185), no difference in the power of astigmatism was apparent between 1 and 3 months postoperatively. The third group (0.75 less than or equal to preoperative AR astigmatism less than 1.5 dptr, n = 143) showed intermediate characteristics. The eyes with preoperative low AR astigmatism showed exacerbation of astigmatism after the PEA procedure, whereas the degree of astigmatism, corneal curvatures and the rate of AR astigmatism became lower in the eyes with higher preoperative AR astigmatism.

Aged

Intraocular muscle function in pseudoexfoliation syndrome.

Pseudoexfoliation (PE) material has been studied pathologically. However, there are no reports about intraocular muscle function in pseudoexfoliation syndrome (PXS). We studied intraocular muscle function in 12 patients (70.3 +/- 10.1 years of age) with ipsilateral PE material by measuring the time course of pupillary diameter change and accommodogram. Initial intraocular pressure (16.3 +/- 4.2 mmHg) was significantly higher in eyes with PXS than in normal fellow eyes (13.1 +/- 3.5 mmHg). The pupillary diameter of an affected eye was smaller than that of a fellow eye after bilateral topical application of tropicamide. Continuous near-point testing revealed no significant difference; accommodative contractile time, relaxation time, and/or accommodopattern showed different patterns from the fellow eye. The results suggest that intraocular muscle function is disturbed in PXS.

Accommodation, Ocular