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Biomedical subjects

N Minato

Publications and source records attributed to N Minato.

At least 19 recordsLinked to original sources

CD3+4-8- alpha beta T cell population with biased T cell receptor V gene usage. Presence in bone marrow and possible involvement of IL-3 for their extrathymic development.

Analysis of TCR of a series of CD4-8- (double negative; DN) alpha beta T cell lines induced with IL-3 revealed that their V gene usage was biased for V alpha 4 and V beta 2. This has been confirmed in the primary short-term cultures. Thus, IL-3 induced the generation of DN alpha beta T cells with predominant V beta 2 gene expression from the CD4+/CD8+ T cell-depleted spleen or bone marrow (BM) cells of both normal and nude BALB/c mice within 10 days. It was further indicated that the V beta 2+ beta-chain genes contained few junctional N regions in both IL-3-induced primary DN alpha beta T cells and continuous lines. Search for the in vivo counterpart of in vitro IL-3-induced DN alpha beta T cells revealed that BM, but not spleens, of normal BALB/c and B6 mice did contain a significant proportion of DN alpha beta T cells, and that the majority of them expressed V beta 2+ beta-chain genes with few junctional N regions. The presence of V beta 2+ DN alpha beta T cells was similarly observed in the BM of BALB/c nude mice, but their proportion varied markedly among various strains of mice, which was not linked to H-2 haplotypes. The results indicated that V beta 2+ DN alpha beta T cells in the BM represented one of the thymus-independent T cell populations, whose development was under the major histocompatibility Ag complex-unlinked genetic control. TCR of these T cells were shown to be functional as judged by the proliferative response to anti-V beta 2 antibody. Taken together, present results suggested that IL-3 could induce differentiation and/or proliferation of DN alpha beta T cells with uniquely limited repertoire, which existed preferentially in BM in vivo, and implied the possible involvement of extrathymic endogenous ligands as a positive selection force.

Animals

One-stage operation for synchronous primary cancers of the lung and the trachea.

A rare combination of synchronous primary adenocarcinoma of the right upper lobe of the lung and adenoid cystic carcinoma of the subglottic trachea was simultaneously managed by lobectomy with lymph node dissection and sleeve resection of the upper trachea through median sternotomy and cervical collar incisions. This combined approach should be a perfectly acceptable one for synchronous tumors of the proximal trachea and of the right upper and middle lobes and left upper lobe of the lung.

Adenocarcinoma

Versatile one-piece total artificial heart for bridge to transplantation or permanent heart replacement.

A versatile, one-piece total artificial heart (TAH) system that can be driven by either an electromechanical acutator (EM-TAH) or a pneumatic source (P-TAH) has been developed. The common units for both TAHs are the conically shaped left and right pusher-plate-type pumps (63 ml SV) that sandwich a thin centerpiece (18 mm) having a respective actuator. The EM actuator, mounted in the middle of the centerpiece, consists of a direct-current brushless motor and a roller screw while the pneumatic actuator consists of a low-pressure air source. The outer diameter of the pumping unit is 97 mm with its central thickness being 82 mm; overall volume is 510 cc. The TAH is operated in the left master alternative ejection mode with the left pump fill signal. High-flex-life Hexsyn rubber is used as the diaphragm, and the blood-contacting surface is coated with dry gelatin. The TAH can provide 3-8 L/min flow with a preload of 1-10 mm Hg against 100 mm Hg afterload. Anatomical fit of the pumping unit has been demonstrated in the pericardial space of 26 heart transplant recipients with average body weight of 78 kg. To date, 2 P-TAH and 4 EM-TAH (1 week) implantations were performed in 80-100 kg calves demonstrating excellent anatomical fit, controllability, and biocompatibility. This versatile TAH is suitable for a bridge to transplantation or permanent heart replacement.

Animals

Potential clinical applications of the oxygen carrying solutions.

Two major areas of research of the oxygen carrying solutions are 1) utilization of hemoglobin and 2) perfluorochemicals. Even though they are not perfect red blood cell substitutes, the "oxygen carrying solutions" have many potential clinical applications because they will reach tissues more easily than normal human red cells and can deliver oxygen directly to tissues. In this paper, important examples of such usages are suggested. Additional clinical and non-clinical applications of the oxygen carrying solutions may be added in the near future.

Artificial Organs

Aortic valve replacement for Takayasu's arteritis.

We report 12 cases of aortic valve replacement performed for Takayasu's arteritis and discuss the genesis of aortic regurgitation and the clinical outcome after aortic valve replacement. This group of twelve patients who underwent aortic valve replacement between April 1982 and March 1990 included four male and eight female patients, aged 24 to 67 years (mean age 48 years). Preoperative angiography showed systemic multiple stenoocclusive or aneurysmal dilated vascular lesions in addition to aortic regurgitation. The multiple lesions included a lesion in the aortic arch branch in nine (75%), in the pulmonary artery in seven (58%), an aneurysmal dilation in the ascending aorta of more than 6 cm in four (33%), a coronary lesion in four (33%), a thoracic aortic lesion in six (50%), and a lesion in the abdominal aorta and its visceral branch in six (50%). Simple aortic valve replacement alone was performed in two patients and in combination with another operation in ten patients, with aortic root reconstruction in two, ascending aortic plication in three, coronary artery bypass grafting in two, aortic arch branch bypass grafting in one, aortic arch branch bypass grafting and coronary ostium endarterectomy in one, and mitral valve replacement and ascending aortic plication in one. There was no operative death, and only one patient died later, 18 months after the operation, because of secondary amyloidosis. The postoperative recovery of the clinical status and cardiac function was good. Intraoperative observations suggested that aortic valve regurgitation may be caused by an extension of aortitis, although histopathologic examinations of the valve showed nonspecific findings. One of the characteristic problems in Takayasu's arteritis is the necessity for prednisolone administration in some patients preoperatively or postoperatively, or both. We conclude that aortic valve replacement for patients with Takayasu's arteritis is an effective and safe treatment. Our data related to the genesis of aortic regurgitation in Takayasu's arteritis remain insufficient to draw conclusions, and further analysis is planned.

Aortic Valve

Direct imaging of the tricuspid valve annular motions by fiberoptic cardioscopy in dogs. I. Does De Vega's annuloplasty preserve the annular motions?

Applying the technology of direct imaging by fiberoptic cardioscopy, physiologic and pathophysiologic motions of the tricuspid valve anulus were studied in 10 anesthetized normal dogs (control group) and in 9 dogs that had chronic tricuspid regurgitation (TR group). The heart was perfused with transparent modified Tyrode's solution by working heart method, and the anuli, outlined by sutured beads, were observed and recorded on a high-speed video system in real time. Tricuspid valve annular area was calculated at 14 points during the cardiac cycle. The control group was studied in the normal condition, and the tricuspid regurgitation group was studied during four interventions: nontricuspid annuloplasty group and three tricuspid annuloplasty groups with reducing tricuspid valve annular area to 80%, 65%, and 50% of that of the non-tricuspid annuloplasty group by De Vega's procedure. Tricuspid valve annular area in the control group increased by 7% during atrial systole and was reduced by 34% mainly during ventricular systole, in which the free wall annular area and the septal annular area narrowed by an equal 34%. Chronic tricuspid regurgitation lessened tricuspid valve annular area narrowing to 20% in percent reduction (p < 0.01). In the TR group the decrease in tricuspid valve annular area narrowing was attributed mainly to lessened narrowing of the free wall anulus (percent reduction of tricuspid valve annular area, 19%; p < 0.01). The amplitudes in tricuspid valve annular area narrowing were unchanged in the tricuspid annuloplasty groups even when tricuspid valve annular area, was reduced to 50% by De Vega's tricuspid annuloplasty (percent reduction of tricuspid valve annular area, 16%; not significant). These findings suggest that De Vega's tricuspid annuloplasty is a reasonable method that does preserve the physiologic annular motions in the opening and closing mechanism of the tricuspid valve.

Animals

Direct imaging of the tricuspid valve annular motions by fiberoptic cardioscopy in dogs with tricuspid regurgitation. II. Does flexible ring annuloplasty preserve the annular motions?

Applying the technology of direct imaging by fiberoptic cardioscopy in a working-heart condition, we studied the tricuspid valve annular motions with flexible rings in nine dogs with chronic tricuspid regurgitation. Three annuloplasty studies with a totally flexible polytetrafluoroethylene ring, an elastic silicone ring, and a rigid metal ring were compared with a nonannuloplasty study. The annuloplasty was performed by reducing tricuspid valve annular area to 65% of that of nonannuloplasty condition. The anuli were observed and recorded on a videotape in real time. The three rings effectively reduced and remodeled the dilated anuli and improved the valve coaptation. The patterns of annular motions with the polytetrafluoroethylene and silicone ring were similar to that of normal anulus; the free wall anulus contracted centripetally, and the septal anulus moved toward the free wall side during systole. Pliability of both the anteroseptal and posteroseptal commissures with the flexible rings made these motions possible. The polytetrafluoroethylene ring followed a natural undulation of the anulus, whereas the silicone and rigid metal rings forced the annular planes to horizontal ones. Percent reductions of tricuspid valve annular area were 25%, 21%, and 23% in the nonannuloplasty, polytetrafluoroethylene, and silicone ring studies, respectively, without significant differences in annular contraction. In contrast, rigid metal rings completely disturbed the annular motions. These findings indicated that the two flexible rings did preserve the physiologic annular motions to the degree that the anuli had in the chronic tricuspid regurgitation condition. Especially, the totally flexible polytetrafluoroethylene ring preserved not only the annular motions but also the natural undulation, which resulted in reinforcing the valve coaptation. We believe that the flexible ring, especially a totally flexible one, is superior to the rigid ring in the aspect of reinforcing the valve coaptation to prevent further regurgitation.

Animals

[Postoperative evaluation of left ventricular peak filling rate and peak ejection rate by radionuclide ventriculography for aortic regurgitation].

Postoperative left ventricular (LV) time-activity curve and the first derivative in radionuclide method were evaluated in 28 patients with aortic regurgitation to clarify the postoperative cardiac function and to determine the adequate timing of operation. Twenty-eight patients were divided into two groups by preoperative echocardiogram. In Group I cases, echo-finding showed LV contractile dysfunction associated with both enlarged LV end-systolic dimension (LVDs) over 5 cm and depressed fractional shortening (%FS) below 25%. In Group II cases, the finding showed compensated cardiac function with relatively small LVDs below 5 cm or not so depressed %FS over 25%. Preoperative diastolic parameter of LV peak filling rate (PFR) in Groups II of 22 cases was depressed in comparison of normal control, although systolic parameters of peak ejection rate (PER) or ejection fraction were mildly depressed. Postoperatively, those parameters of PFR and PER were improved to normal control level (1. PFR: pre op = 206 +/- 73----post op = 311 +/- 79, p less than 0.001 2. PER: pre op = 309 +/- 65----post op = 389 +/- 103 %EDV/sec. p less than 0.001). In contrast, the preoperative parameters of PFR and PER in Group I of 6 cases were strikingly impaired, and post-operative those parameters were not improved to normal level (1. PFR: op = 154 +/- 39----post op = 190 +/- 88 2. PER: pre op = 223 +/- 74----post op = 244 +/- 78 %EDV/sec, NS). No postoperative complications occurred in Group II cases, in contrast, 2 cases in Group I were complicated with low output syndrome or ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve Insufficiency

High-molecular-weight Ly-5 isoforms expressed on T cells: activation-dependent expression.

Interleukin 2 (IL-2)-dependent granular T lymphocyte (GTL) lines derived from murine spleen were shown to express a Ly-5 antigen with the so-called 'B220-epitope' recognized by 6B2 mAbs, which were normally exhibited on B-lineage cells. Immunoprecipitation analysis revealed that the Ly-5 isoform on GTL lines represented the highest-molecular-weight Ly-5 so far described (260 kd), distinct from the B220 isoform on a pre-B cell line (240 kd). The size difference between them was also evident after the endoglycosidase treatment (210 versus 190 kd), strongly suggesting that these Ly-5 isoforms had core proteins of distinct size. Sequential immunoprecipitation by 6B2 and 14.8 mAbs further indicated that the 260 kd Ly-5 on GTL lines predominantly expressed '6B2 epitope' while '14.8 epitope' dominated in the B220 (240 kd) on a pre-B cell line. Northern blot analysis of the Ly-5 transcripts using probes for the known alternative exons failed to show any evidence for mRNA of the 260 kd Ly-5 distinct from that of B220. Polymerase chain reaction analysis, however, suggested that the 260 kd isoform mRNA might be transcribed from a distinct promoter with a yet undefined exon(s). The 6B2+ Ly-5 isoform was hardly detected on normal splenic T cells, but was shown to be induced rapidly on the majority of T cells following IL-2 stimulation in vitro, indicating that this particular Ly-5 isoform behaved as an 'activation antigen' on T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Interleukin 7 preferentially supports the growth of gamma delta T cell receptor-bearing T cells from fetal thymocytes in vitro.

Murine fetal thymus cells were cultured with various interleukins (IL-1, 2, 3, 4, 5, 6, and 7) in the absence or presence of phorbol 12-myristate 13-acetate (PMA), and it was found that only IL-4 and IL-7 induced a prominent proliferative response in the presence of PMA. A large proportion of cells grown in the cultures of fetal thymus cells (days 15 and 17 of gestation) stimulated with PMA plus IL-4 or with PMA plus IL-2 remained CD4-CD8-. In marked contrast, nearly 70% of the cells generated in the cultures of the same fetal thymocytes stimulated with PMA plus IL-7 expressed CD8 on their surface. Approximately 30% of these cells expressed TCR gamma, delta, whereas TCR alpha beta+ cells were virtually undetectable. The cells grown in cultures stimulated with PMA plus IL-7 comprised three populations: CD4-Lyt-2-3-, CD4-Lyt-2 + Lyt-3- and CD4-Lyt-2 + Lyt-3+, and that TCR gamma delta+ T cells were found in all three populations. It was also found that the addition of IL-7 in the culture of adult CD4-CD8- thymocytes on the monolayer of a thymic stromal cell line, which selectively promotes the generation of alpha beta T cells, resulted in the generation of gamma delta T cells. These results strongly suggest that IL-7 plays an important role in the development of gamma delta T cells.

Animals

Evaluation of left ventricular early diastolic function after coronary artery bypass grafting relating to myocardial damage.

This clinical study was undertaken to evaluate resting left ventricular early diastolic function relating to perioperative myocardial damage after coronary artery bypass graft (CABG) with radionuclide ventriculography. Forty-eight cases undergoing CABG were divided into two groups--Group I: not complicated with perioperative myocardial infarction (PMI), and Group II: complicated with PMI. In group I (42 cases), early diastolic parameters such as peak filling rate (1/3 PFR) and mean filling rate (1/3 FR(m)) during first third diastole were not impaired in the postoperative and follow up periods. In contrast, in Group II (6 cases), early diastolic parameters were significantly decreased to 157 +/- 74% EDV/sec of 1/3 PFR(pre op: 234 +/- 74, p less than 0.05) and 153 +/- 80% EVD/sec of 1/3 FR(m) (pre op: 231 +/- 86, p less than 0.05) in the postoperative period, and these parameters were still decreased in follow up period. The time to peak filling rate, normalized to diastolic time (TPFR/DT) of Group II cases, was severely prolonged in both periods. From these results, the complication of perioperative myocardial infarction was suggested by the decrease of early diastolic function and the prolongation of the time to peak filling rate. Early diastolic function was a more sensitive parameter than systolic function in the detection of impaired cardiac function in those cases with perioperative myocardial damage after CABG.

Adult

[A case of primary Sjögren's syndrome presenting as osteomalacia secondary to renal tubular acidosis].

We report a 43-year-old female with primary Sjögren's syndrome (SjS) who presented as osteomalacia due to distal renal tubular acidosis (RTA). Osteomalacia was thought to be a rare complication of RTA in SjS, although it had been often described in association with RTA in general. In 1979, she presented with dry mouth, parotid gland swelling and leg purpura. A diagnosis of primary SjS and hyperglobulinemic purpura was made on the basis of positive staining with Rose Bengal stain, sialography of the parotid gland and histological examination of the salivary gland of the lip. She was admitted to Jichi Medical School Hospital in March 1988 with chest pain. X-ray films revealed pseudofractures of bilateral ribs. Bone scanning showed abnormal multiple accumulation of RI on the same parts. Laboratory studies on admission revealed: GOT 50 IU/ml, GPT 9 IU/ml, ALP 190 IU/ml, LDH 301 IU/ml, BUN 11.0 mg/dl, creatinine 1.0 mg/dl, uric acid 2.7 mg/dl, total protein 7.4 g/dl (gamma globulin 22.3%), sodium 141 mEq/l, potassium 3.7 mEq/l, chloride 106 mEq/l, calcium 8.9 mg/dl, and phosphorus 2.4 mg/dl. Arterial blood gas studies on room air showed: PO2 96.7mmHg, PCO2 35.5mmHg, HCO3-19.1 mEq/l, PH 7.347 and base excess -5.4 mEq/l. The urinalysis showed: specific gravity 1.008, PH 7.0, and no protein and glucose. Immunologically, antinuclear antibody was positive at 1:640 with a speckled pattern. Anti-DNA antibody was negative. Antibodies to SS.A and SS.B were 1:64 and 1:32 respectively. Distal RTA was confirmed by the sodium bicarbonate and NH4Cl loading test.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Renal Tubular

Identification and gene cloning of a new phosphatidylinositol-linked antigen expressed on mature lymphocytes. Down-regulation by lymphocyte activation.

Lymphocytes are shown to express a limited number of a unique category of membrane Ag, such as Thy-1, Ly-6, Ly-31, and Qa-2, that are covalently linked to the membrane phosphatidylinositol (PI). We have identified a new glycosyl-phosphatidylinositol (GPI)-anchored lymphocyte Ag, B7, by using a mAb and have determined the primary structure by cDNA cloning. B7 Ag was expressed on the majority, if not all, of the mature lymphocytes of both T and B lineages, including strongly CD3+ thymocytes, most splenic T cells, and approximately 60% of splenic IgM+ B cells, whereas the expression of B7 Ag on bone marrow cells was negligible. The expression of B7 Ag was nearly completely abolished with as little as 2 mU of PI-specific phospholipase C per ml, which did not completely eliminate Ly-6C and Thy-1 expression. Unlike the expression of other GPI-linked lymphocyte Ag, the expression of B7 was rapidly down-regulated upon the activation of T cells by mitogens or IL-2 both in vitro and in vivo. Immunoprecipitation analysis revealed that B7 Ag was an approximately 12-kDa protein. With a CDM8 expression vector, a cDNA encoding B7 Ag was cloned, and it was confirmed that the B7 Ag on cDNA-transfected cells was indeed PI-specific phospholipase C sensitive. The B7 cDNA contained an open reading frame of 222 bp including a typical N-terminal leader sequence and a characteristic sequence at the C terminus encoding hydrophobic amino acids. A computer search revealed no significant homology to any known molecule at both DNA and amino acid sequence levels. Northern blot analysis indicated that the B7 transcript was expressed on lymphohematopoietic tissues, including thymus, spleen, and bone marrow, but not on other organs, such as liver, kidney, and brain. The results indicated that B7 Ag is a new member of the GPI-anchored proteins which is selectively expressed on mature resting but not activated lymphocytes.

Amino Acid Sequence

Expression of murine IL-2 receptor beta-chain on thymic and splenic lymphocyte subpopulations as revealed by the IL-2-induced proliferative response in human IL-2 receptor alpha-chain transgenic mice.

Lymphocytes from the human (h) IL-2R alpha chain transgenic mice (TGM) constitutively express high affinity binding sites for hIL-2, consisting of transgenic h-IL-2R alpha and endogenous murine IL-2R beta, and therefore easily proliferate in vitro in response to hIL-2. Our study was undertaken to clarify the hIL-2-responsive lymphocyte subsets in the TGM, which should most likely reflect the normal distribution of m IL-2R beta expression. In both thymus and spleen, the majority of expanded cells by hIL-2 was CD3+CD4-CD8+ TCR alpha beta+ cells. The proliferation of CD4+ cells was not observed at all from either organ despite the expression of transgenic hIL-2R alpha. Potent cellular proliferation was also observed from the thymocytes that had been depleted of CD8+ cells, the expanded cells consisting of CD3- (15-40%) and CD3+ populations (60-85%). Among CD3+ cells, approximately the half portion expressed TCR alpha beta, whereas the other half was suggested to express TCR gamma delta. A variable portion (5-20%) of the CD3+ cells expressed CD8 (Lyt-2) in the absence of Lyt-3, and the CD3+CD8+ cells were confined preferentially to the TCR alpha beta- (TCR gamma delta+) population. In the culture of splenocytes depleted of CD8+ cells, however, the proliferated cells were mostly CD3-CD4-CD8-TCR-Mac1-, whereas a minor portion (10-30%) was CD3+CD4-CD8-TCR alpha beta- (TCR gamma delta+. Analysis of TCR genes at both DNA and mRNA levels confirmed the phenotypical observations. These results strongly suggested that IL-2R beta was constitutively and selectively expressed on the primary murine thymocytes and splenic T and NK cells, except for CD4+ cells in both organs.

Animals

Analysis of natural killer activity and natural killer cell subsets in patients with bladder cancer.

In order to analyze the state of the natural resistance system of bladder cancer patients in vivo, we measured natural killer (NK) activity and NK cell subsets of peripheral blood lymphocytes (PBL) from 46 patients with bladder cancer and 25 age- and sex-matched healthy volunteers. The mean NK activity in patients with low-stage bladder cancer was similar to that in the controls, while NK activity in patients with high-stage bladder cancer was significantly depressed. The mean proportions of Leu7+ cells in patients with both low-stage and high-stage bladder cancer were significantly higher than that in the controls. The mean proportion of Leu11 a+ cells in patients with low-stage bladder cancer was similar to that in the controls, while in patients with high-stage bladder cancer it was significantly higher. This study demonstrates the abnormal immunological state of bladder cancer patients: namely, abnormalities exist not only in NK activity but also in the proportions of circulating NK cell subsets.

Antibodies, Monoclonal