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Biomedical subjects

Y Asano

Publications and source records attributed to Y Asano.

At least 559 records · Page 31Linked to original sources

Synergistic T-T cell interaction present in alloreactivity: determination of 'MLR helper' T cell subsets.

CD4 and CD8 T cell subsets involved in primary allo-MLR responses were re-evaluated in the present study. The slope analysis of B6 allo-MLR responses to MHC class I-disparate bm1 and class II-disparate bm12 revealed the presence of a T-T cell interaction between CD4 and CD8 T cell subsets. The allo-MLR response of B6 CD4 T cells to bm12 was completely blocked by anti-L3T4, indicating that the function of CD4 T cells is required for allo-MLR responses to bm12. It was further demonstrated that the function of CD8 T cells in class II-disparate allo-MLR is to augment the proliferative response of CD4 T cells. On the other hand, CD8 T cells primarily responded to class I-disparate allo-MLR, and CD4 T cells function to augment the proliferative response of CD8 T cells. It was further indicated that CD4 and CD8 T cells recognize both class I and class II MHC. The CD4 T cell recognition of allo-class I and CD8 T cell recognition of allo-class II induces insufficient signals for proliferation of these T cells. Thus, the class I-reactive CD4 and class II-reactive CD8 T cell subsets function as helper cells ('MLR helper' T cells) for proliferating T cells in MLR responses.

Animals↗

Cell division-associated expression of an epitope, KH17, on early developing thymocytes.

A newly established monoclonal antibody, KH17, detects a unique epitope temporarily expressed on early developing CD3-thymocytes confined to a cycling stage. KH17 is detectable on a part of CD4-CD8-,CD4-CD8+, and CD4+CD8+ cells, but not on CD4+CD8- thymocytes. By four-color flow cytometry analysis using KH17, we were able to define the heterogeneity of immature CD4-CD8- thymocytes by the expression of KH17 and IL-2R. In Thy-1-congeneic bone marrow chimeras, the appearance of KH17-IL-2R+ thymocytes preceded the increase of KH17+IL-2R- cells. The antibody could also divide CD3-CD4-CD8+ cells into two subpopulations, KH17+ and KH17-, which showed a continuum. In the fetal thymus there was a rapid and dramatic increase of KH17-CD4+CD8+ thymocytes concomitant with a decrease of KH17+CD4-CD8+ thymocytes in later gestation days. KH17 is not expressed on resting peripheral T cells, but is expressed on a large proportion of Con A-activated blastic spleen cells. The KH17 molecules precipitated from Con A-activated spleen cells were 55 and 75 kd polypeptides, but different from IL-2R subunits.

Animals↗

T cell clones are killed by a thymic stromal cell monolayer following stimulation of T cell receptor with antigen and/or H-2 molecules on the monolayer.

A thymic stromal cell clone, MRL104.8a, expressed class I and class II H-2k antigens after exposure to gamma-interferon (gamma-IFN) and produced thymic stroma-derived T cell growth factor (TSTGF) irrespective of gamma-IFN exposure. Culturing the keyhole limpet hemocyanin (KLH)-specific, I-Ek-restricted 9-16 helper T cell (Th) clone on an Ia (I-Ak and I-Ek)-expressing MRL 104.8a monolayer induced potent proliferation of the 9-16 cells by virtue of the TSTGF produced by the monolayer. In contrast, the addition of KLH to cultures resulted in lethal growth inhibition of the 9-16 Th clone. Such a phenomenon was also observed for various Th as well as cytotoxic T lymphocyte (CTL) clones, and the following were revealed: (i) the growth of the ovalbumin (OVA)-or bovine thyroglobulin (BTg)-specific Th clone on the la-expressing MRL 104.8a monolayer was also inhibited by addition of the relevant antigen. The fact that these Th clones required antigen-presenting cells (APC) capable of processing antigen for the recognition of the respective target antigen suggested the potential of MRL 104.8a cells for antigen-processing; (ii) the lethal growth inhibition of KLH-specific, I-Ak (23-1-8)- or I-Ek (9-16)-restricted Th clone was prevented selectively by anti-I-Ak or anti-I-Ek antibody respectively; (iii) the I-Ek-alloreactive Th clone (2-13) was supported for its growth on a gamma-IFN-unexposed MRL 104.8a monolayer, whereas this clone was killed on an I-Ek-expressing monolayer; and (iv) when I-Ak-reactive CTL clones were cultured on an Ia- or Ia+ monolayer, CTL clones failed to exhibit cytotoxic effect on either the Ia- or the Ia+ monolayer, but were conversely killed by the Ia+ monolayer. Its killing was also prevented by an antibody which inhibits the recognition of Ia antigen on the monolayer by CTL clones.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Analysis of age-related degeneracy of T-cell repertoire: localized functional failure in CD8+ T cells.

The repertoire and frequency of alloreactive T cells in aged mice were examined by limiting dilution analysis of the mixed-lymphocyte reaction (MLR). Mice were aged in specific pathogen-free conditions up to 31 months, and MLR of their spleen cells under limiting dilution conditions was examined at various stages of ageing. The frequency of alloreactive T cells was found to decrease in mice more than 14 months of age, and the value reached about 1/3 of that of young mice of 2 months of age. The slope analysis of cell dose-response curves of MLR indicated the existence of two interacting T-cell populations, i.e. CD4+ and CD8+, cooperation between which is required for the full manifestation of MLR in limiting dilution conditions. The decrease in the alloreactivity of aged spleen cells was ascribed to the selective functional loss of the CD8+ population, because the CD4+ but not the CD8+ T-cell fraction from aged mice could restore the limiting factor in MLR. The decrease in the cooperative activity of CD8+ T cells in allo-MLR starts much earlier than the decrease in the number of CD8+ T cells in the spleen.

Aging↗

Microlamellar structures in lobular glomerulonephritis associated with monoclonal IgG lambda paraproteinemia. A case report and review of the literature.

We report a 49-year-old woman who developed lobular glomerulonephritis with prevalent deposition of material positive for IgG, C1q and lambda light chain, but which was not stained by Congo red. Glomeruli revealed massive electron-dense deposits with a microlamellar structure in the mesangial matrix and peripheral capillary loops. Clinically, the patient had nephrotic syndrome, microhematuria and hypertension. No Bence-Jones protein or cryoglobulin was found in the urine or serum. Anti-DNA antibody was positive, but systemic lupus erythematosus (SLE) was ruled out by repeated serological examinations. Immunoelectrophoresis of blood and urine revealed increased IgG-lambda paraprotein, but no free light chains were found. We reviewed 54 cases reported in the literature, which showed organized crystalline structures on ultrastructural examination, but were unassociated with amyloidosis, SLE, cryoglobulinemia or multiple myeloma. The present patient is the first reported to have exhibited a combination of glomerulonephritis with organized deposits, monoclonal IgG lambda paraproteinemia, and the presence of anti-DNA antibody.

Female↗

Age-related degeneracy of T cell repertoire: influence of the aged environment on T cell allorecognition.

The present study was undertaken to understand the mechanism of alteration of the alloreactivity of T cells in aged mice. The experiment utilized bone marrow chimeras revealed that the age-associated changes in alloreactivity are not primarily determined by the bone marrow stem cells but determined by the environment where stem cells differentiate into mature T cells. The limiting dilution analysis and microfluorometry analysis indicated that the changes lie in both frequency of alloreactive T cells and the expression of T cell antigen receptor. Such quantitative and qualitative changes seems to be the causes for declined alloreactivity of T cells in aged mice.

Age Factors↗

Epitope-specific regulation of the antibody response against alpha-lactalbumins in the mouse.

The immune responsiveness to human and bovine alpha-lactalbumin (HuALA and BoALA) was found to be under the control of immune response (Ir) gene(s) linked to the major histocompatibility complex. H-2k mice responded to both HuALA and BoALA, whereas H-2d,s,and f mice respond only to HuALA; H-2b mice were nonresponders to both HuALA and BoALA. A survey with B10.A recombinant mouse strains enabled us to map the Ir gene in the I-A subregion. The responsiveness was shown to be dominant in F1 mice. The coimmunization of BoALA and HuALA resulted in the suppressed secondary antibody response to HuALA in B10.S (H-2s) and BALB/c (H-2d) but not in C3H (H-2k) suggesting that the low responsiveness against HuALA in these strains is due to an active suppression. The transfer of splenic T cells of B10.S mice primed with BoALA into syngeneic animals suppressed the response to HuALA. T cells specific for a particular epitope present on BoALA appeared to suppress the immune response to other epitopes on HuALA. Thus, the presence of epitope-specific suppressor T cells seems to account for this Ir-gene-controlled low responsiveness to ALA in H-2s mice.

Amino Acid Sequence↗

Electrophysiological identification of alpha- and beta-intercalated cells and their distribution along the rabbit distal nephron segments.

By cable analysis and intracellular microelectrode impalement in the in vitro perfused renal tubule, we identified alpha- and beta-intercalated (IC) cells along the rabbit distal nephron segments, including the connecting tubule (CNT), the cortical collecting duct (CCD), and the outer medullary collecting duct in the inner stripe (OMCDi). IC cells were distinguished from collecting duct (CD) cells by a relatively low basolateral membrane potential (VB), a higher fractional apical membrane resistance, and apparent high Cl- conductances of the basolateral membrane. Two functionally different subtypes of IC cells in the CCD were identified based on different responses of VB upon reduction of the perfusate Cl- from 120 to 12 mM: the basolateral membrane of beta-IC cells was hyperpolarized, whereas that of alpha-IC cells was unchanged. This is in accord with the hypothesis that the apical membrane of beta-IC cells contains some Cl(-)-dependent entry processes, possibly a Cl-/HCO3- exchanger. Further characterization of electrical properties of both subtypes of IC cells were performed upon lowering bath or perfusate Cl- from 120 to 12 mM, and raising bath or perfusate K+ from 5 to 50 mM. A 10-fold increase in the perfusate K+ had no effect on VB in both subtypes of IC cells. Upon abrupt changes in Cl- or K+ concentration in the bath, a large or a small depolarization of the basolateral membrane, respectively, was observed in both subtypes of IC cells. The electrical properties of alpha- and beta-IC cells were similar among the distal nephron segments, but their distribution was different: in the CNT, which consists of IC cells and CNT cells, 97.3% (36/37) of IC cells were of the beta type. In the CCD, which consists of IC cells and CD cells, 79.8% (79/99) of IC cells were of the beta-type, whereas in the OMCDi 100% (19/19) were of the alpha type, suggesting that the beta type predominates in the earlier and the alpha type in the later segment.

Animals↗

Behavioural characteristics of wild jumping or running episodes in the double mutant spontaneously epileptic rat.

Spontaneously epileptic rats (SER) are homozygous for two mutations, zitter (zi) and tremor (tm), and spontaneously exhibit both absence-like seizure and tonic convulsion. In addition, wild jumping or running episodes sometimes appear without any previous stimuli. We recorded the behaviour on a video camera and/or a vibration response apparatus to examine the behavioural characteristics. All wild jumping or running episodes appeared within 27 s after termination of tonic convulsion with a frequency of 2.1%, and the episode could be detected even in the dark by using the vibration response apparatus. A rapid increase of high motor activity around the episodes was recorded as a single peak with high amplitude by the vibration response apparatus. The wild jumping or running episode appeared in all 4 SER at 8-14 weeks of age with a variable frequency, 0-9 times in the light period and 0-6.7 times in the dark period 8 h each week. Thus, the wild jumping or running episode was found to occur not only during the light period but also during the dark period without any significant difference in frequency.

Animals↗

Delayed postnatal behavioral development in spontaneously epileptic rats and tremor rats, and poor operant performance in spontaneously epileptic rats.

Postnatal behavioral development and learning ability of operant performance were examined in spontaneously epileptic rats (SER: zi/zi, tm/tm), and the original tremorous mutant strains of rats, tremor rats (tm/tm) and zitter rats (zi/zi) and their controls. Before the eyes opened, the increase in body weight and the age of achieving the righting reflex on a surface were no significantly different between the SER and their littermates without epileptic seizures (SER-N: zi/zi, tm/+ or zi/zi, +/+), and between tremor rats and the original strain Kyo: Wistar rats. After the eyes opened, the increase in body weight, age of achieving the righting reflex in air and traction performance, and the development of rotarod performance, were delayed in SER and tremor rats in comparison with other groups of rats. The zitter rats were apparently inferior in their development of rotarod performance in comparison with the same zitter homozygous SER-N. Operant performance was more inferior in SER than in SER-N and in tremor rats than in Kyo: Wistar rats. The differences were much more marked between SER and SER-N than between tremor and Kyo: Wistar rats. Thus, homologous tm genes and the coexistence of homologous tm and zi genes have an inhibitory effect on postnatal behavioral development and learning ability.

Animals↗

Sensitivity of spontaneously epileptic rats to external stimuli that induce seizures.

The sensitivity of spontaneously epileptic rats (SER), double homozygotes of zitter and tremor mutations, to external stimuli that induce seizures was studied in comparison with tremor (tm/tm) and zitter (zi/zi) rats, and with normal Kyo: Wistar and F 344/N rats. Touching their body, a blinking light (1200 lux, 1 sec interval) or a big sound (8 and 12 kHz, 95 dB) induced tonic extension only in the SER. The response frequency was 22 to 44% at 9 weeks of age and 75 to 100% at 13 weeks of age. Electric stimulus at 30 mA induced tonic-clonic convulsions in all Kyo: Wistar and F 344/N rats. At 20 mA the incidence of seizures decreased with age, from 100% at 5 weeks of age to 33% at 13 weeks of age in Kyo: Wistar rats and from 100 to 71% in F344/N rats. In SER, 10-mA stimuli induced tonic extension at 9 and 13 weeks of age, and 20 and 30 mA induced tonic convulsions, generalized or partial convulsions, and wild jumping or running episodes at 5, 9 and 13 weeks of age. At 30 mA, the incidence of convulsive seizures decreased with age in both tremor (tm/tm) and zitter (zi/zi) rats. Apparently external stimuli acted as simple triggers in the induction of tonic extension, since characteristic tonic extension is induced in the SER by each of the stimuli used in the present study, and induced convulsions closely resembled spontaneously occurring convulsions. The threshold of external stimuli in the induction of tonic extension became lower with aging in the SER, indicating that they are appropriate models for evaluating anticonvulsant drugs, as reported previously.

Acoustic Stimulation↗

[Effects of long-term administration of furosemide on calcium balance, kidney and parathyroid gland].

Furosemide, a potent natriuretic agent, is well known to increase urinary calcium excretion. We study the effects of long term administration of furosemide on the calcium balance, renal function and histopathological changes of the kidneys and the parathyroid glands in the rat. Furosemide (20 mg/kg) was administered 3-4 times per week for 62 weeks intraperitoneally in 10 male rats. The same volume of normal saline was administered intraperitoneally in 9 male rats as control. All were given with standard diet (CE-2) and deionized water. While urinary calcium and creatinine were measured every 1-4 weeks, serum calcium and creatinine were measured in the first week and at the end of examination. 24 hours urinary excretion of calcium was elevated to two to three folds (a significant increase over the control: p less than 0.01) after the furosemide loading, though serum calcium and creatinine levels remained as in control. Despite a marked hypercalciuria in the furosemide loaded rats, there was no evidence of stone formation in the kidney or in the urinary tract. On histopathological examination renal parenchyma showed some pyelonephritic changes but without evidence of crystal formation, while no significant change was noted in the parathyroid glands. Based on these data we concluded that in our model, 1) there was a significant calcium loss in the absence of any change in the serum calcium, but 2) this hypercalciuria alone was not lithogenic, and 3) parathyroid glands showed no discernible secondary morphological changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[A study on sex chromosome mosaicism--endocrinological and immunohistochemical findings with glutathion S-transferase in the gonads].

In order to clarify the clinical aspects of sex chromosomal mosaicism, we evaluated the karyotypes, the anatomy of external genitalia and internal ductal system, the pituitary-gonadal function, and the histopathology of the gonads by immuno-staining for glutathion S-transferase (GST) in 5 patients who had been all raised as female. Three patients have the 45, X/46, XYq- karyotype in the initial lymphocyte culture or the subsequent culture of skin fibroblasts. Another two karyotypes were 45, X/46, XYq-/47, XYq-, Yq- and 45, X/46, XdicY. Thus, Y chromosome of all patients retained short arms in which the testis determining factor is encoded. Three prepubertal patients were referred to us for their ambigious external genitalia and two postpubertal patients were for the short statures. Although the vaginal orifice was separated from the urethral meatus in all of them, the phallic enlargement was noted in 4 patients and the posterior labial fusion in 2 patients. The oldest patient had a normal female appearance of external genitalia except the vaginal septum. Serum gonadotrophin (GnH) levels were basically high in the postopubertal patients and the responses of GnH to LH-RH were significantly increased in the prepubertal patients. Serum testosterone levels to hCG stimulation ranged from no response to low normal response. All patients underwent the exploratory laparotomy together with the feminizing genitoplasty. The gonads in 3 patients, diagnosed as mixed gonadal dysgenesis (MGD), consisted of a unilateral testis and a contralateral streak gonad. Two patients had variants, including one with bilateral dysgenetic testis and another with bilateral streak gonads.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Treatment of urological anomalies detected by prenatal ultrasonography].

By the recent advance in ultrasonography, an increasing number of patients with prenatally detected urological anomalies have been reported. Herein, we present 19 cases experienced in the last 3 years in our institution and review the problems in their diagnosis and treatment. In all cases but 2 ultrasonography revealed fetal abnormalities after the 30th gestational week. No cases with abnormal amniotic fluid or severe fetal growth retardation were experienced. No cases were treated in utero. However, 7 cases required an early delivery because of progressive hydronephrosis or enlargement of tumor mass. Postnatally 6 cases were treated by emergency drainage such as percutaneous nephrostomy and placement of an indwelling catheter. However most of the cases with proven urinary tract dilatation were evaluated by diuretic renogram and followed conservatively thereafter. In equivocal cases, pressure-flow study was added. Spontaneous involution of multicystic kidney was also experienced. Erroneous interpretation can occur in fetal diagnosis and the accuracy of prenatal diagnosis was 52.6% in our series. In determining the management of prenatally detected urological anomalies, several factors such as reliability of ultrasonography, fetal renal function, maturity of the lung and the volume of amniotic fluid, must be taken into consideration. Considering the increasing number of fetuses thus detected, it is very important for the pediatric urologists to make consensus on the fetal intervention and postnatal management.

Female↗

Drug sensitivity test for acute myeloblastic leukemia by an efficient leukemic blast colony assay using 5637-conditioned medium as a stimulator.

Drug sensitivity of clonogenic leukemic blast cells was measured using the leukemic blast colony formation technique. Each of three chemotherapeutic agents, cytosine arabinoside, daunorubicin and aclarubicin, was added at the start of culture, and sensitivity was measured in terms of numbers of surviving leukemic blast colonies formed under continuous exposure to the drug. A substantial number of colonies was observed in all cases examined when the conditioned medium of human bladder carcinoma cell line 5637 was used as the leukemic blast colony stimulator. Although drug sensitivity varied considerably among the cases examined, sensitivity to administered drugs in clinical non-responders was significantly poorer than that in clinical responders (p less than 0.05).

Aclarubicin↗

[Quantitation of absolute and relative renal uptake using 99mTc-DMSA: sequential change in time and correlation with 99mTc-DTPA uptake].

A renal uptake of 99mTc-DMSA as a function of time and correlation between 99mTc-DMSA and 99mTc-DTPA in renal uptake were discussed. The absolute renal uptake of 99mTc-DMSA calculated by complete correction of tissue attenuation and physical decay showed increase by 5 hours after the administration, except one case with congestive heart failure. The net renal counts attained a maximum between 2 to 3 hours after the administration. There was a good correlation (r -0.992, p less than 0.001) between the relative renal uptake of 99mTc-DMSA (2 hour) and that of 99mTc-DTPA (2-3 min). On the contrary, the absolute renal uptake of 99mTc-DMSA as a indicator of total renal function showed a poor correlation (r = 0.419) to GFR calculated from 99mTc-DTPA. The results indicate that the relative renal uptake of 99mTc-DMSA is a reliable quantitative parameter for split renal function. However, the absolute renal uptake of 99mTc-DMSA may be suggested to be a different renal functioning indicator from GFR calculated from 99mTc-DTPA.

Adolescent↗

Hyponatremia and hyperreninemic hypoaldosteronism in a critically ill patient: combination of insensitivity to angiotensin II and tubular unresponsiveness to mineralocorticoid.

A 62-year-old man with pneumonia and left flank pain had a clinical syndrome of hyponatremia, hypotension, dehydration, and high urinary sodium excretion in the presence of a normal glomerular filtration rate. The plasma level of antidiuretic hormone was relatively high despite decreased serum osmolality. Thyroid function and excretion of glucocorticoid and sex steroids were normal. The serum aldosterone level was very low despite elevated plasma renin activity. Angiotensin II failed to stimulate any secretion of aldosterone, despite the occurrence of a progressive rise in blood pressure. On the other hand, rapid ACTH administration increased both serum aldosterone and cortisol. The patient showed no effective response to increased salt intake, but large doses of mineralocorticoid resulted in a normal serum sodium level without dehydration. Subsequently, he suffered cardiac arrest secondary to ventricular tachycardia. Postmortem examination showed well differentiated adenocarcinoma in the left pleura and an intact, histologically normal adrenal zona glomerulosa and kidney. This is the first reported case of a critically ill patient with hyponatremia caused by hyperreninemic hypoaldosteronism possibly due to angiotensin II insensitivity and tubular unresponsiveness to mineralocorticoid.

Adrenal Glands↗