Biomedical subjects

M Inaba

Publications and source records attributed to M Inaba.

At least 307 records · Page 17Linked to original sources

PubMed1991

Ontogeny of thymic B cells in normal mice.

Ontogeny of thymic B cells and their surface characteristics were analyzed using monoclonal antibodies (mAbs) against B220 molecules (CD45, CD45R). A small number of B cells were detected in fetal thymus on Gestation Day 14 (approximately 3.5% of the low-density fraction). Similarly, the percentage of B cells in the low-density fraction was 3.2% on Gestation Day 18, and 3.5% on Day 1 after birth. These were the same level as that of adult mice. CD5+ B cells, which form the major population of thymic B cells, were also found in the fetal life (0.5% on Day 14 and 2.2% on Day 16 in the low-density cells). The percentage of CD5+ B cells in B cell-enriched fraction was about 65% on Day 1 after birth, which is the same level as that in adult mice. These results indicate that a small number of B cells or cells in the B-cell lineage are present in the fetal thymus and also suggest the importance of these thymic B cells in the negative selection of T cells during early developmental stages.

Animals↗

PubMed1991

Neonatal tolerance induction in the thymus to MHC-class II-associated antigens. IV. Significance of intrathymic chimerism of blood-born Ia+ cells in Mls tolerance.

The significance of thymus cell chimerism in the induction and maintenance of tolerance was investigated. Mls-1b BALB/c mice were neonatally tolerized by the intravenous administration of either bone marrow (BM) cells or peritoneal cavity (PerC) cells from Mls-1b/a (BALB/c x AKR) F1 mice. Tolerance was long-lasting in the BM cell group, but transient in the PerC cell group, probably because PerC cells lack hemopoietic stem cells required for a continuous supply of tolerance-inducing cells. The degree of anti-Mls-1a responsiveness of these BALB/c thymus cells was correlated with the degree of intrathymic distribution of the inoculated F1 cells. The effect of BM cell inoculation, resulting in a year-long deletion of Mls-1a-reactive V beta 6-bearing T cells is in marked contrast to that of PerC cell inoculation which causes only a transient loss of V beta 6+ mature thymocytes (for about 1 week after birth). This functional profile of the tolerant state correlates well with the degree and persistence of the intrathymic presence of F1 type Ia+ cells. The long-lasting presence of donor-derived cells throughout the thymus tissue in the BM cell group is also in marked contrast to the early disappearance of Ia+ cells (within 2-3 weeks) from the cortex and then from the medulla in the PerC cell group, although these Ia+ cells were once spread throughout the thymus tissue 4 days after the tolerance-inducing cell inoculation. Taken together with a failure to induce consistent unresponsiveness to Mls-1a determinants in Mls-1b thymocytes regenerating in Mls-1a-thymic epithelial environments, all the above data indicate that intrathymic chimerism caused by hemopoietic stem cell-derived MHC-class II-bearing cells is a requisite for the induction and maintenance of unresponsiveness by means of clonal deletion in experimentally as well as naturally induced tolerance to Mls determinants.

Animals↗

PubMed1991

Hereditary high-potassium erythrocytes with high Na, K-ATPase activity in Japanese shiba dogs.

The sodium (Na) and potassium (K) concentrations and Na, K-ATPase activity were examined in erythrocytes from 24 Japanese shiba dogs and 79 dogs of 24 other breeds. Eleven of the shibas had erythrocytes with high K and low Na concentrations, together with high Na, K-ATPase activity (HK RBCs), while red cells from the remaining shibas and all of the other breeds examined showed low K and high Na concentrations, with no enzyme activity (LK RBCs). The concentration of reduced glutathione in HK RBCs was about five times that in LK RBCs. All the findings from HK shibas were in good agreement with those from HK mongrel dogs found in Japan previously. Since the shiba is a Japanese breed of dog, the results of the present study strongly suggest that the gene for HK RBCs may be inherent in dogs indigenous to Japan, particularly in shiba dogs.

Animals↗

PubMed1991

Effect of alpha 1-blockade on diminished forearm blood flow in diabetics.

An increased risk of atherosclerotic disease has been reported in patients with diabetes mellitus. The present study was therefore designed to determine forearm blood flow (FBF) in patients with essential hypertension or those with diabetes mellitus with or without hypertension. FBF determined by venous occlusion plethysmography decreased with age in controls as well as in patients with essential hypertension, whereas FBF in diabetics was significantly lower irrespective of age or blood pressure. As a result, vascular resistance was significantly higher in diabetics than in controls or patients with essential hypertension. Glycemic control in normotensive diabetics during 3 weeks significantly augmented a diminished FBF. alpha 1-Blockade by oral administration of 1 mg of prazosin also augmented the diminished FBF in diabetics, in association with a significant decrease in mean blood pressure and vascular resistance. These results suggest that FBF may be a simple and useful index for determining arterial and/or venous distensibility, and that alpha 1-blocker therapy, in addition to glycemic control, may be a first-line antihypertensive treatment for diabetics with associated hypertension.

Administration, Oral↗

PubMed1991

Effect of dietary calcium on renal prostaglandins.

The present study was designed to clarify the possible role of renal prostaglandins (PGs) on blood pressure (BP) regulation during calcium (Ca) restriction or supplementation. Twelve normotensive women with a mean age of 21.2 years participated in the study. After 1 week of normal Ca intake (mean +/- SE, 536 +/- 2 mg/day), a low-Ca diet (163 +/- 1 mg/day) was given for a further 1 week. Additional asparagine Ca (3 g as Ca/day) was also given to half of the subjects. BP, heart rate, and serum total and ionized Ca concentrations were measured at the end of each period. Levels of Ca, sodium, PGE2, 6-keto-PGF1 alpha and thromboxane (TX) B2 excreted into urine were also determined. The plasma level of ionized Ca was significantly increased without any change in total Ca in both groups. Low and high Ca intake decreased and increased urinary Ca excretion by 28% and 56%, respectively. BP was not altered after Ca deprivation or loading. However, urinary PGE2 excretion was significantly augmented from 668.9 +/- 68.1 to 959.7 +/- 183.1 ng/day by Ca loading, whereas Ca deprivation decreased PGE2 excretion (695.4 +/- 108.1 to 513.2 +/- 55.2 ng/day). No changes were observed in 6-keto-PGF1 alpha or TXB2 urinary excretion. These results suggest that renal PGE2 synthesis is stimulated or decreased by 1-week Ca loading or deprivation, indicating a possible antihypertensive role of renal PGE2 during high-Ca intake in hypertensives.

6-Ketoprostaglandin F1 alpha↗

PubMed1991

Characterization of B cells in human thymus.

The surface characteristics of B cells present in the human thymus were investigated. Cytofluorometrical and immunohistological studies, using anti-human IgM or anti-B cell monoclonal antibodies (mAbs; anti-Leu 12Ab, anti-Leu 16Ab, or L26), revealed that a small number of B cells are present in the human thymus. The thymic B cells were detected only in a low-density cell population, whereas in a high-density cell fraction, only T cells were found. In 15 cases, all of which the thymi were histologically normal, the percentages of B cells in the low-density fraction were 0.28% to 50% (6.8% in average), and Leu 1+ (CD5+) B cells in the low-density fraction were 0.1% to 26% (3.5% in average); approximately 50% of the thymic B cells were Leu 1+ B cells. These results indicate that B cells, especially Leu 1 (CD5)+ B cells, are also present in the human thymus, as suggested from our previous reports on mice.

Adolescent↗

PubMed1991

Monoclonal antibodies against a preadipose cell line (MC3T3-G2/PA6) which can support hemopoiesis.

Monoclonal antibodies against a mouse preadipose cell line (MC3T3-G2/PA6:PA6), which can support hemopoiesis by direct cell-to-cell interaction, were produced and characterized. The antibodies react with PA6 but not PA6-M (a mutant cell line) which has the capacity neither to contact with hemopoietic stem cells (HSCs) nor to support hemopoiesis. Endosteal cells in the bone marrow show positive staining to these antibodies. They inhibit pseudoemperipolesis of PA6 to HSCs, resulting in a significant decrease in hemopoietic cell number. These findings suggest that the monoclonal antibodies bind to the stromal cell receptors for HSCs and block the binding of HSCs to stromal cells leading to suppression of hemopoiesis.

Adipose Tissue↗

PubMed1991

Provirus integration at the 3' region of N-myc in cell lines established from thymic lymphomas spontaneously formed in AKR mice and a [(BALB/c x B6)F1----AKR] bone marrow chimera.

Among 18 thymic leukemia cell lines which have been established from spontaneous thymic lymphomas in AKR mice as well as in bone marrow chimeras which were constructed by transplanting allogeneic bone marrow cells into irradiated AKR mice, three proviral integration sites were identified; near c-myc, N-myc and pim-1 loci. No integration site specific for chimeric leukemia cell lines was found. In three thymic leukemia cell lines which contained rearranged N-myc genes, insertions of long terminal repeats (LTRs) of murine leukemia viruses were detected at 18 or 20 bp downstream of the translational termination codon. These results demonstrate that the 3' region of the N-myc gene is one of the integration targets for murine leukemia viruses in spontaneous thymic lymphomas. In these three cell lines, N-myc mRNA was stably transcribed and transcription of c-myc mRNA was down-regulated. The integrated murine leukemia viruses in AKR thymic leukemia were most likely AKV, though the DNA sequence of the LTR inserted in the genome of a leukemic cell line from [(BALB/c x B6)F1----AKR], CAK20, was different from LTRs of murine leukemia viruses so far reported.

Antigens, Surface↗

PubMed1991

Uremic serum contains humoral factor(s) larger than fifty kilodaltons which suppresses endothelin production in cultured endothelial cells.

Direct effects of human uremic serum on the production of endothelin-1 in cultured porcine endothelial cells were examined in this study. Uremic serum decreased the level of monomeric endothelin-1 secreted into the culture medium by endothelial cells. This effect occurred at a transcriptional step because uremic serum decreased the endothelin-1 mRNA level in those cells. For the partial characterization of this inhibitory activity, uremic serum was fractionated with a centricut column. Uremic serum contains humoral factor(s) larger than 50 kD which suppress the endothelin-1 mRNA level in cultured endothelial cells.

Animals↗

PubMed1991

Significance of proteolytic activity in 1,25-(OH)2D3-induced differentiation of HL-60 cells.

Two types of HL-60 cells, 1,25-(OH)2D3-responsive ATCC HL-60 cells and 1,25-(OH)2D3-resistant LG HL-60 cells were used. Despite the presence of enough amounts of normal 1,25-(OH)2D3 receptors, only 22% of LG cells matured after a 4-day treatment with 10(-7) M 1,25-(OH)2D3, while 80% of ATCC cells differentiated. However, 1,25-(OH)2D3 inhibited the proliferation of LG cells to the same degree as that of ATCC cells. 1,25-(OH)2D3 also induced (1) the ability to metabolize 1,25-(OH)2D3 to 1,24,25-(OH)3D3, and (2) up-regulation of the 1,25-(OH)2D3 receptor in LG as well as ATCC cells. Furthermore, the proportion of mature LG cells was 78% after treatment with 10(-7) M 1,25-(OH)2D3 for the first 48 h and 10(-7) M dbcAMP for the second 48 h, which was greater than that when treated only with 10(-7) M dbcAMP for the second 48 h (24.2%). These results indicate that 1,25-(OH)2D3 receptor complexes function normally in LG cells at commitment step in cell differentiation. ATCC cells had a serine proteinase to destroy specific 1,25-(OH)2D3-binding activity of the unoccupied receptor and digest 53-kD receptor to a small fragment with a MW of 16.3 kD, while not affecting the level of the specific binding of the occupied receptor. Other cells, such as murine leukemia cells, M1, and human chronic myeloid leukemia cells, the differentiation of which is induced by 1,25-(OH)2D3, seemed to have the same type of proteinase, suggesting the physiological significance of this proteinase in 1,25-(OH)2D3-induced cell differentiation.

Bucladesine↗

PubMed1991

Mechanism for resistance to 5-fluorouracil in P388 leukemia cells.

In order to assess mechanisms for acquired resistance to 5-fluorouracil (5-FU) of P388 cells on a cellular basis, we compared sensitivities of P388 and its 5-FU-resistant subline (P388/5-FU) cells to 5-FU, 5-fluorouridine (FUrd) and 5-fluoro-2'-deoxyuridine (FdUrd). P388/5-FU cells exhibited an approximately 10-fold resistance to 5-FU and 170-fold cross-resistance to FUrd but not to FdUrd when they were exposed to each agent for 5 h in vitro. 5-FU-induced growth inhibition was hardly reversed with thymidine, suggesting its ribonucleic acid (RNA)-directed effect. This was supported by the fact that similar amounts of 5-FU were incorporated into cellular RNA in P388 and P388/5-FU when these cells were incubated with equitoxic concentrations of 5-FU. Furthermore, incorporation of 5-FU and FUrd into cellular RNA in P388/5-FU cells were significantly lower than in P388 cells when cells were exposed to them at the same concentration. These results suggest a major action of 5-FU is directed toward RNA in these cells at least under the present experimental condition, and 5-FU resistance of this cell line is closely associated with reduced uridine kinase activity among various enzymatic changes previously observed.

Animals↗

PubMed1991

Design and synthesis of antitumor compounds based on the cytotoxic diterpenoids from the genus Rabdosia.

Two active sites responsible for antitumor activity, an oxirane ring and an alpha-methylene-cyclopentanone moiety, have been extracted from studies on the structure-activity relationship of the cytotoxic diterpenoids isolated from Rabdosia shikokiana. Series of the simplified cyclopentanone derivatives containing both of the two active sites in the molecule have been synthesized and evaluated for cytotoxicity against P 388 cells. The compounds possessing both of two active sites displayed cytotoxicity at a concentration of 1 microgram/ml, while those possessing a single active site showed no activity.

Animals↗

PubMed1991

Cryoglobulinemia in a horse.

Cryoglobulin was isolated from a horse which had glomerulo-nephritis and a history of swelling and skin ulcers of the limbs in the winter. The isolated cryoglobulin showed a single peak on a gel permeation chromatography column with an apparent molecular mass (Mr) of 180,000 which could be divided into two gamma bands by cellulose acetate electrophoresis. Immunoelectrophoretic analysis revealed that the cryoglobulin formed two precipitation lines with anti-horse IgG. Spur formation was observed when the cryoglobulin and the IgG purified from a normal healthy horse were cross-reacted with anti-horse IgG on a double diffusion gel. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis under the reduced conditions showed that the isolated cryoglobulin consisted of two doublets of polypeptides with Mr values of 52,000 and 50,000, and 31,000, and 30,000, corresponding to the heavy chain and the light chain of the horse IgG molecules, respectively. These results suggest that the isolated cryoglobulin might consist of two different IgG molecules, and that the manifestations such as foot swelling with skin ulcers and renal failures were all induced by the cryoglobulin in the serum.

Animals↗

PubMed1991

Effect of dietary calcium on serum BGP (osteocalcin).

The present study was designed to clarify the effects of dietary calcium (Ca) intake on serum BGP (osteocalcin) levels. Twelve women with a mean age of 21.2 years participated in the study. After one week of normal Ca intake (mean +/- SE, 535 +/- 2 mg/day), a low-Ca diet (163 +/- 1 mg/day) was given for one further week. Additional asparagine Ca (3 g as Ca/day) was also given to half of the subjects. Serum total and ionized Ca concentrations as well as BGP, PTH and 1,25(OH)2D3 were measured at the end of each period. Amounts of Ca and hydroxyproline excreted in urine were also determined. The plasma level of ionized Ca was significantly increased without any change in total Ca in either group. Low and high Ca intake decreased and increased urinary Ca excretion by 28% and 56%, respectively. Serum levels of BGP and 1,25(OH)2D3 were significantly augmented along with a transient increase in urinary hydroxyproline excretion after Ca deprivation. These results suggest that serum BGP is increased after one week of Ca restriction in healthy subjects.

Adult↗

PubMed1991

Effects of arginine vasopressin on blood pressure and renal prostaglandin E2 in rabbits.

The role of arginine vasopressin (AVP) in blood pressure regulation in humans and animals is still controversial. The present study was designed to investigate the effects of AVP on blood pressure and the excretion of sodium and prostaglandin (PG) E2 in rabbits. AVP dissolved in 0.01 M acetic acid was infused subcutaneously at a rate of 0.86 ng/kg/min with a miniosmotic pump into 12 New Zealand white rabbits (2.7-3.4 kg), while 10 controls were given vehicle alone. AVP infusion resulted in a 3.5-fold rise in the level of plasma AVP (21.8 +/- 4.4 (SEM) pg/ml) as compared with controls, associated with a significant decrease in the urine volume and urinary excretion of sodium. The PGE2 excretion was increased 1.8-fold after AVP infusion. In the chronic AVP-infused group, blood pressure was not significantly increased, but the acute vascular response to AVP was significantly attenuated without any changes in the vasopressor response to angiotensin II. Preadministration of V1-antagonist completely abolished the vasopressor action of AVP, but not that of angiotensin II, in either group. These results suggest that circulating AVP within physiological range of concentrations may stimulate renal PGE2 synthesis and attenuate the vascular response through vascular V1 receptors without affecting the baroreflex, which may be attenuated through V2 receptors.

Angiotensin II↗

PubMed1991

Effects of slow-release nifedipine on nighttime blood pressure.

With the advent of long-acting or slow-release antihypertensive drugs, we should be aware of a fall in nighttime blood pressure (BP) as well as daytime blood pressure. In the present study, casual BPs at the physician's office as well as ambulatory BP was recorded every hour throughout 24 hours with a noninvasive automated BP monitoring device in 24 essential hypertensives treated with slow-release nifedipine. Administration of slow-release nifedipine (20-40 mg, b.i.d.) decreased not only casual BPs but also ambulatory mean BP during the whole day or daytime (6 am to 10 pm). Slow-release nifedipine at 10 mg in the morning did not affect casual BPs at the office. However, mean BP obtained by ambulatory BP monitoring during the daytime was significantly attenuated. In addition, a profound fall in mean BP amounting to more than 20 mmHg during the night in some of the patients was observed during treatment with slow-release nifedipine not only at 20-40 mg (b.i.d.) but also at 10 mg once a day. These results suggest that we have to take into consideration the possibility that long-acting hypotensive agents may cause a great fall in nighttime BP during sleep, especially in the elderly.

Adult↗

PubMed1991

Clinical significance of ambulatory blood pressure monitoring. Evaluation of severity of hypertension, efficacy of treatment and effects on nighttime blood pressure.

Blood pressure (BP) obtained by the physician in his office and ambulatory BP recorded every hour throughout 24 hours with a noninvasive automated BP monitoring device were compared in 10 normotensives and 162 hypertensives. Casual BPs significantly correlated with averages in ambulatory BPs (ABPs) throughout the whole day, day (7 am - 10 pm) and night (0-5 am). However, it was noted that 6 of 10 normotensives and all of the moderate to severe hypertensives had ABPs of more than 150/90 mmHg at least once during the 24-hour period. The incidence of ABPs greater than 150/90 mmHg among all readings was higher in untreated and treated hypertensives with diastolic BPs in the office of more than 105 mmHg, and, when checked along with the clock time, higher not only in the morning but also in the evening. On the other hand, one-third or one-fifth of treated hypertensives with diastolic office BPs less than 90 mmHg or between 90 and 105 mmHg respectively had ABPs less than 150/90 mmHg throughout the whole day. When the effect of nicardipine (60 mg, t.i.d.) or slow-release nifedipine (27.3 +/- 3.0 mg, b.i.d.) on minimum BP during the night was analyzed, long-acting nifedipine decreased BP throughout the night to levels not significantly different from normotensive controls, whereas short-acting nicardipine did not affect nighttime BPs. These results suggest that simple ABP monitoring throughout the day gives us useful information to evaluate the severity of hypertension and the efficacy of antihypertensive medication as well as to avoid overtreatment with long-acting hypotensive agents resulting in a great fall in BP during sleep.

Blood Pressure Determination↗

PubMed1991

Effects of uremic serum on 1,25-dihydroxyvitamin D3-induced differentiation of a human promyelocytic leukemia cell line, HL-60.

The mechanism by which resistance to 1,25 dihydroxyvitamin D3 (1,25-(OH)2D3) occurs in patients with chronic renal failure was studied. This agent induces differentiation and 1,25-(OH)2D3-24-hydroxylase activity in the mitochondria of the human promyelocytic leukemia cell line, HL-60, via a steroid-hormone receptor mechanism. HL-60 cells were cultured in RPMI 1640 medium supplemented with 10% normal or uremic serum. Treatment of these cells with 10(-8)M 1,25-(OH)2D3 for 5 days in a medium containing 10% uremic serum from 4 patients with chronic renal failure resulted in a maturation of the cells amounting to 30.3 +/- 18.7% (mean +/- SD) and 32.5 +/- 11.2%, as obtained by NBT reduction assay and NSE assay, respectively. These values were significantly lower than those obtained with 10% serum from 3 normal controls (66.6 +/- 12.8%, 58.3 +/- 10.9%, p less than 0.02). The treatment of HL-60 cells with 1,25-(OH)2D3 in a mixture of 5% normal plus 5% uremic serum caused cell differentiation to an extent similar to that in 10% uremic serum, which suggests the presence of a substance(s) having 1,25-(OH)2D3-inhibitory activity in the uremic serum. Exposure of HL-60 cells to uremic serum significantly impaired their responsiveness to 1,25-(OH)2D3 as assessed by the induction of the cell's ability to hydroxylate the C-24 position of 1,25-(OH)2[3H]D3. The mechanism by which uremic serum confers an impaired cellular response to 1,25-(OH)2D3 seemed to be due, in part, to a decrease in 1,25-(OH)2D3 receptor levels. A significant positive correlation was observed between intracellular cAMP levels and 1,25-(OH)2D3-induced HL-60 cell maturation. In summary, the mechanism by which uremic serum confers 1,25-(OH)2D3 resistance upon HL-60 cells seemed to be due to the presence of 1,25-(OH)2D3-inhibitory activity in uremic serum, which may modulate cellular responsiveness to 1,25-(OH)2D3 by such mechanisms as reducing 1,25-(OH)2D3 receptor levels in the cells, in part through alteration in cAMP metabolism.

Adult↗