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Biomedical subjects

T Masuda

Publications and source records attributed to T Masuda.

At least 469 records · Page 26Linked to original sources

Synergistic infectivity of highly and minimally infectious clones of human immunodeficiency virus in vitro.

To explore the biologic significance of the presence of a heterogeneous human immunodeficiency virus (HIV) population within infected individuals with regard to ultimate disease progression, the effect of coinfection of more than one variant of HIV on infectivity and cytopathogenicity in CD4-positive cells was examined. Using the lowest and highest infectious clones of HIV obtained by the plaque-cloning method, a clear consistent synergism of infectivity and cytopathic effects was detected when different cell lines were coinfected with a mixture of the two clones. These data suggest that the emergence of a highly infectious variant of HIV due to mutation may modify the infectivity of a minimally infectious latent variant with the final progression of HIV infection to overt AIDS.

Cell Line↗

Interaction between two distinct plaque-cloned human immunodeficiency viruses (HIVs): the possible existence of heterozygous virus.

To know the biological significance of the HIV variation, we investigated the interaction between two different HIV clones. Two distinct clones were mixed and propagated by infecting MT-4 cells. After passaging the mixture viruses 8 times, and cloning by the plaque method, we obtained not only viruses of homogeneous type like each parental clone but also heterogeneous-type viruses which showed a mixture of two parental viruses with regard to phenotype and genotype. To further segregate a single virus from the mixture, we recloned the heterogeneous viruses using the plaque method. We found that about 40% of recloned viruses from heterogeneous-type viruses were still heterogeneous.

Animals↗

Application of monoclonal antibodies to the detection of black-pigmented Bacteroides spp. in subgingival plaques by immunoslot blot assay.

The aim of the present study was to assess the application of monoclonal antibodies to the detection of black-pigmented Bacteroides spp. in subgingival plaques by immunoslot blot assay. Subgingival plaque samples from adult periodontal patients were examined by immunoslot blot assay with monoclonal antibodies that specifically recognize Bacteroides gingivalis, Bacteroides intermedius serogroups I and II, and Bacteroides melaninogenicus. The assay can detect specifically these Bacteroides spp. in the subgingival plaques. Therefore, we investigated the distribution of these Bacteroides spp. in the subgingival plaques of patients classified by Russell's periodontal index. Reactivities of their plaques with monoclonal antibodies toward B. gingivalis and B. intermedius serogroup I were clearly related to the severity of the periodontal disease, but this was not the case with B. intermedius serogroup II and B. melaninogenicus. These results indicate that this immunoslot blot assay using monoclonal antibodies toward these Bacteroides spp. provides simple detection and monitoring of these organisms in periodontal patients.

Adult↗

Interference with human immunodeficiency virus (HIV) replication by CD8+ T cells in peripheral blood leukocytes of asymptomatic HIV carriers in vitro.

A long asymptomatic period is one of the characteristics of human immunodeficiency virus (HIV) infection, despite its fatal consequences. Antiviral defense in HIV-infected individuals controls viral replication during this period. In the present study, we demonstrate that peripheral blood leukocytes (PBL) of asymptomatic HIV-1 carriers, following exogenous HIV-1 infection in vitro, do not support viral replication. These cells do not produce detectable amounts of reverse transcriptase or accumulate unintegrated proviral DNA. This is a striking contrast to the behavior of HIV-1-infected PBL of seronegative individuals, which produce large amounts of RT and unintegrated DNA. Such resistance to HIV-1 replication is not seen in PBL of patients with advanced disease. Since the binding of HIV-1 to CD4 molecule is not impaired in PBL of asymptomatic carriers, the interference with HIV replication must occur after the stage of virus binding. PBL lose their resistance when CD8+ lymphocytes are removed. In addition, these PBL are not resistant to an exogenous infection with HIV-2. These observations suggest that certain populations of CD8+ lymphocytes of asymptomatic HIV-1 carriers operate on the target cells in PBL to block viral replication in an HIV-1-specific manner. Such CD8+ lymphocyte-mediated interference with HIV replication could play an important role in the maintenance of the period of disease latency.

AIDS-Related Complex↗

Intracellular calcium concentration of acinar cells in feline tracheal submucosal glands.

We measured the intracellular free calcium ion concentration [( Ca2+]i) of acinar cells in isolated feline tracheal submucosal glands in response to secretagogues using the Ca2(+)-sensitive fluorescent dye fura-2. The secretagogues included cholinergic, adrenergic agonists, substance P (SP), and vasoactive intestinal polypeptide (VIP) which induce mucus glycoprotein secretion from feline tracheal submucosal glands. Methacholine (MCh) produced a significant increase in [Ca2+]i of up to 9.8 times that of control in a dose-dependent fashion at concentrations of 10(-8) to 10(-3) M. [Ca2+]i increase by MCh reached a peak within 30 s after stimulation and thereafter showed a sustained rise. In Ca2(+)-free medium, MCh produced an initial transient rise, which was less than 30% of that in a Ca2(+)-containing solution, and which lasted for 60 s with no prolonged sustained rise in [Ca2+]i. Atropine abolished MCh-evoked [Ca2+]i increase. Phenylephrine and SP produced a prolonged increase in [Ca2+]i without an initial transient increase. Phenylephrine (up to 10(-4) M) evoked an increase in [Ca2+]i by up to 240% that of control, which was abolished by prazosin. SP (up to 10(-4) M) also evoked an increase in [Ca2+]i by 155% that of control, which was abolished by atropine. By contrast, both isoproterenol (up to 10(-5) M) and VIP (up to 10(-5) M) failed to alter [Ca2+]i. These findings indicate that the mucus glycoprotein secretion evoked by muscarinic cholinergic, alpha-adrenergic agonist or SP can be mediated by intracellular Ca2+, whereas that by beta-adrenergic agonists or VIP cannot.

Animals↗

Effects of easily chewable diet and unilateral extraction of upper molars on the masseter muscle in developing mice.

The effects of easily chewable diets and unilateral extraction of upper molars on the masseter muscle were studied in developing mice. A liquid diet requiring no mastication suppressed the development of the masseter muscles more than a fine-grained diet, and extraction of unilateral upper molars also caused inhibition of muscle development. Moreover, both unilateral extraction of upper molars and a liquid diet had an additive effect on the suppression of the postnatal development of the masseter muscle, and bilateral suppression of the development of the masseter muscle was induced following unilateral extraction of upper molars. These findings suggest that the sensory input from the sensory endings in the periodontal ligament may also play an important role in the postnatal development of the masseter muscle and that there may be some crossing pathways to convey the sensory input coming from the side of the extracted upper molars to the contralateral motor neurons via the interneuronal circuits.

Animals↗

Hemodynamic changes by recombinant erythropoietin therapy in hemodialyzed patients.

Recombinant human erythropoietin therapy was given to 15 patients undergoing long-term hemodialysis with normal cardiac function. None of the patients had hypertension before the erythropoietin therapy and had received no antihypertensive agents. Before and after the erythropoietin therapy M-mode and pulsed Doppler echocardiographic studies, measurements of plasma volume by radioiodinated human serum albumin, and measurements of atrial natriuretic factor were carried out. After 6 weeks of erythropoietin therapy, hematocrit increased from 20.0 to 33.0%. Cardiac output, stroke volume, left ventricular diastolic dimensions, and left ventricular wall stress were all significantly decreased. Total peripheral resistance, interventricular septal thickness, and left ventricular posterior wall thickness were significantly increased. In Doppler echocardiographic studies, the mean velocity of aortic ejection flow and left ventricular acceleration time were decreased. The blood volume derived from plasma volume and hematocrit was not changed, whereas plasma atrial natriuretic factor concentration was significantly decreased. These data suggest that recombinant human erythropoietin administration suppressed the hyperdynamic cardiac state that was required to maintain oxygen delivery to the peripheral tissues in severe uremic anemia.

Adult↗

Identification of activated T cell receptor gamma delta lymphocytes in the liver of tumor-bearing hosts.

T cell receptor (TcR)gamma delta cells are known to be a minor population of T lymphocytes in the blood (less than 10%) and other peripheral lymphoid organs in healthy donors. We demonstrated here that a large proportion of TcR gamma delta cells, i.e., up to 30% of mononuclear cells (MNC) were detectable in the liver, but not other lymphoid organs of cancer patients. More importantly, the majority of such TcR gamma delta cells (greater than 70%) were shown to be lymphoblastic by electron microscopy. An activation marker of T lymphocytes, Leu-19 (CD56) was also highly expressed on the hepatic TcR gamma delta cells. The possibility of hepatic TcR gamma delta cells being activated was further examined in mice. C3H/He mice injected with syngeneic tumor cells were demonstrated to have an increased number of liver MNC; such MNC showed an ability to proliferate in vitro. These mice eventually had a considerable proportion of TcR gamma delta cells in the liver, showing activation markers, the Ia and LFA-1 antigens. These results suggest that the liver may be an important organ for activation and probably expansion of TcR gamma delta cells especially in tumor bearing hosts.

Animals↗

Structural and functional alterations of mesenteric vascular beds in spontaneously hypertensive rats.

The morphology and reactivity of mesenteric arteries from spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY) were investigated. Isolated, perfused mesenteric vascular beds were prepared from 6-, 11- and 18-week-old SHR and WKY. At these ages, the walls and media of large mesenteric arteries were significantly thicker in SHR than in WKY. The number of smooth muscle cell layers in the media was significantly larger in SHR than in WKY. This difference between SHR and WKY increased as rats grew older, in parallel with differences in the blood pressure. Flow rate-perfusion pressure curves indicated that the vascular basal resistance to flow increased more profoundly in SHR preparations than in WKY preparations as rats grew older. This may be related to the structural alterations of the resistance vessel wall in SHR. The pressor responses to KCl were greater in SHR preparations than in WKY preparations as rats grew older. This may be caused partly by the increase of the number of smooth muscle cell layers in the media of SHR resistance vessels. The pressor response to norepinephrine (NE) was significantly higher in SHR preparations than in WKY preparations at all ages investigated. In marked contrast to the vascular basal resistance and the pressor response to KCl, the pressor response to NE was extremely exaggerated in SHR at the age of 6 weeks. This extremely high NE response in younger SHR may not be caused by the structural alteration in resistance vessels. It may be caused by a functional change, which is regulated by the signal transduction process in smooth muscle cells of resistance vessels. These results suggest that the development of hypertension in SHR may be caused by genetic structural and functional abnormalities of resistance vessels. Both abnormalities may be caused by the hyperreactivity to NE through an altered signal transduction process in smooth muscle cells of resistance vessels in SHR.

Analysis of Variance↗

[Long-term bioeffects of extracorporeal shock waves on renal tissue and blood pressure in normotensive and spontaneously hypertensive rats].

In order to examine chronic effects of shock waves on renal structure and blood pressure, normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were uninephrectomized and shock waves were given on the lower half of the residual kidney by Piezolith with the focus pressure of 1020 bar. In the first experiment, 36 WKY were divided into 6 groups; Group 1 served as control, Group 2, 4 and 6 received a single session of 1250, 2500 and 5000 shocks, respectively, whereas the animals in Group 3 and 5 received repeated dose of 1250 or 2500 shocks within 3 days after the first session. All the animals in Group 6 died within 48 hours due to remarkable renal hemorrhage, leaving only 5 Groups for the evaluation of long-term study. The blood pressure, measured by tail-cuff method 60 days after shock wave administration, was not significantly different between the control and shock-waved WKY. Neither was there any remarkable difference between the blood pressures measured prior to and 60 days after the intervention in each Group. At 16th week after the shock wave administration, the animals were sacrificed. There was a slight but statistically significant increase in serum creatinine level in Groups 2, 4 and 5, as compared to the level of control animals in Group 1. On light microscopic sections, there was no remarkable histological change in the kidney of Group 2, however, the renal parenchyma was frequently replaced with interstitial fibrosis in Groups 3, 4 and 5.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Airway hyperresponsiveness and mucus secretion].

A large amount of mucus and mucoid impaction are observed in the autopsied lungs of bronchial asthmatics. It is possible that mucus hypersecretion and accumulation of intrabronchial mucus result in bronchial obstruction and structural bronchial hyperresponsiveness. Bronchial gland plays a main role in human airway secretion. We describe here some results using isolated gland preparation which enable us to examine airway mucus secretion in a well-defined condition. Chemical mediators released from mast cells augment the secretory responses induced by cholinergic nerve stimulation through accelerated acetylcholine release in the nerve terminals. PAF produces an increase in mucus glycoprotein secretion in the presence of platelets mainly through the thromboxane release from platelets. Substance P which is released by an axon reflex in response to various stimuli and inflammations in the airways, also produced an increase in mucus secretion. Epithelial cells release an inhibitory factor to mucus glycoprotein secretion from bronchial glands. Epithelial cell damages due to inflammation in the airways may induced a reduction of the inhibitory factor release in bronchial asthmatics, resulting in mucus hypersecretion.

Asthma↗

[Involvements of neuropeptides in pentylenetetrazol-induced convulsion in rats and effects of TRH and ceruletide on the convulsion].

To study the possible involvements of neuropeptides in the occurrence of convulsion, pentylenetetrazol (PTZ) was given to male Wistar rats weighing 250-350 g, and the concentration of neurotensin (NT), and the maximal number of binding sites (Bmax) and dissociation constant (Kd) of NT receptor in the frontal cortex were measured. The effect of the pretreatment of thyrotropin-releasing hormone (TRH) or ceruletide (CER) on the convulsion was also studied. NT was extracted from the homogenates of rat frontal cortex by boiling, and measured by radioimmunoassay. Membrane fractions were incubated with increasing concentrations of 125I-NT. Nonspecific binding was determined in the presence of unlabeled NT and subtracted from total binding to obtain the specific binding. The Bmax and Kd were calculated by Scatchard analysis. Generalized convulsion appeared after intraperitoneal administration of 50 mg/kg PTZ with a latency of 68.2 +/- 4.4 sec. One hour after the administration, neurotensin-like immunoreactivity (NTLI) concentration was reduced from 4.7 +/- 0.6 to 2.3 +/- 0.1 ng/g wet wt (p less than 0.01) and the Bmax of NT receptor from 17.2 +/- 2.8 to 10.8 +/- 1.1 fmol/mg protein (p less than 0.01). However no significant changes were observed in somatostatin-like immunoreactivity (SSLI) concentration and the Bmax and Kd of SS receptor. These facts indicate that PTZ stimulates the release of NT resulting in down regulation of NT receptor. Pretreatment with intracerebroventricular (icv) administration of 30 micrograms/10 microliters NT 30 min before the 50 mg/kg PTZ administration shortened the duration of the convulsion from 135.0 +/- 42.8 to 11.5 +/- 11.9 sec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Clinical results of sequential and "Y" grafting with the internal mammary artery].

One hundred and sixty-five patients (125 men, 40 women; age ranged from 40 to 81 years), underwent coronary artery bypass grafting in the 3 years period from 1986 to 1988. The internal mammary artery (IMA) was applied to 125 patients (75.8%). The sequential left IMA grafting to the left anterior descending coronary artery (LAD) and the diagonal branch (Dg) was performed in 9 out of 125 patients. In 3 of 9 patients, the right IMA was simultaneously grafted to the obtuse marginal branch (OM). In situ bilateral IMAs grafting to the LAD and Dg or LAD and OM were used in 13 patients. In three patients, "Y" grafting (the free right IMA was anastomosed to the side of the in situ left IMA) was performed for LAD and Dg. Eighty-one of 82 IMA grafts (99%) were patent about 1 month after operation. Three patients (1.8%) died during hospitalization, one from Low Output Syndrome, two from cerebral infarction. Perioperative complication included myocardial infarction in 5 (3.0%), cerebral infarction in 10 (6.0%). We concluded that the IMA could be applied in multivessel grafting as well as single vessel grafting in severe diffuse coronary artery disease in the Japanese, and the early patency was good even in the sequential and "Y" grafting.

Adult↗

[Left ventricular asynergy and myocardial necrosis accompanied by subarachnoid hemorrhage: contribution of neurogenic pulmonary edema].

One hundred-thirty patients with acute subarachnoid hemorrhages were investigated to examine the relationship of neurogenic pulmonary edema to cardiac lesions. Abnormal electrocardiograms were observed in 99 of these patients. Left ventricular asynergy was detected in nine of the 99 patients by two-dimensional (2D) echocardiography. In addition to 2D echocardiography, chest radiography, electrocardiography, serum CPK measurements and cardiac catheterization were performed for these nine patients in the acute stages of their subarachnoid hemorrhages. Abnormal electrocardiographic findings included prolongation of QT intervals and marked ST-T changes, which were observed in all nine patients. Pulmonary edema associated with increased pulmonary arterial wedge pressures were noted in seven, and increases in CPK and MB-CPK in all patients, suggesting the occurrence of myocardial necrosis. An increase in serum catecholamine was observed in all patients. Coronary angiography was performed in two patients and revealed normal coronary arteries in both. Biopsy findings were available in three and demonstrated severe fragmentation at the sites of left ventricular asynergy. Pulmonary edema, electrocardiographic abnormalities and left ventricular asynergy improved markedly during the courses of hospitalization. We concluded that left ventricular asynergy and myocardial necrosis may occur during the acute stage of subarachnoid hemorrhage and could produce neurogenic pulmonary edema rather than or in addition to permeability edema.

Adult↗

[A study of combined chemotherapy with MMC, ADM, CDDP, etoposide (VP-16), 5'DFUR (MAC-VD therapy) in advanced cancer and local relapse of the stomach].

Eighteen patients with progressive/locally recurrent cancer of the stomach were given therapy with MMC, ADM, CDDP, Etoposide (VP-16), and 5'DFUR (MAC-VD therapy). Drugs were administered intravenously with MMC 10 mg/m2, ADM 20 mg/m2, and CDDP 50 mg/m2 on day 1; orally with etoposide 100 mg/day for five consecutive days from day 3; and orally with 5'DFUR 600 mg/day for three weeks from day 3 followed by discontinuation for one subsequent week. This drug regimen was one course of the treatment and repeated as far as possible. There were 16 evaluable cases; the sex distribution was ten males and six females. Patients ranged in age from 43 to 78 years. P.S. 1 was two cases; 2 ten cases; and 3 four cases. The overall response rate, CR + PR, was 1 + 7/16 (50%), while this rate for primary disease was 2 + 5/16 (43.8%). Of the two CR cases, one primary lesion became operable and CR was demonstrated histologically. The overall response rates, CR + PR, for metastatic lesions were 1 + 3/9 (44.4%) for the liver; 0 + 1/4 (25.0%) for the abdominal lymph nodes; 0 + 1/2 (50.0%) for the superficial lymph nodes; 0 + 1/2 (50.0%) for the bones; and 0 + 1/1 (100%) for the lung. The median duration of the response was 3.7 months (range between 1.5 and 8.2+) and the median duration of survival 5.1+ months (range between 2.2+ and 13.3+). At the same time, the hematological side effects of both leukocytopenia and hypohemoglobinemia were seen in 43.8% of the cases. Non-hematological side effects included alopecia in 18.8% and nausea/vomiting in 12.5%. There was no case of discontinuation due to side effects. It was concluded that the therapy with MMC, ADM, CDDP, etoposide and 5'DFUR (MAC-VD therapy) proved to be a very promising drug regimen in the treatment of stomach cancer with high rates of response and is expected to be a step forward in the establishment of interdisciplinary treatment.

Administration, Oral↗

[The changes in tumor markers such as serum CEA, CA 19-9, TPA and CA 125 in the chemotherapy of patients with advanced gastric cancer].

Twenty-five patients with advanced gastric cancer were treated with a combination chemotherapy. The levels of serum CEA, CA 19-9, TPA and CA 125 were measured before and during chemotherapy (4 and 8 weeks). One complete and 10 partial responses were obtained, and the response rate was 44%. Pretreatment positive rates of these four tumor markers were all more than 60%, and the positive rate of combination assay was 96%. The mean percent changes of these four tumor markers were similar and correlated well with the response to chemotherapy. There was a significant correlation between tumor reduction and decrease of serum CEA in the responders with measurable lesions. These results suggest that the measurement of changes of serum tumor markers may be useful for monitoring the response to chemotherapy in patients with gastric cancer. It also may be useful to determine early the effectiveness of the treatment.

Adolescent↗