Biomedical subjects

Y Imai

Publications and source records attributed to Y Imai.

At least 865 records · Page 48Linked to original sources

PubMed1990

Replacing the carboxy-terminal 28 residues of rabbit liver P-450 (laurate (omega-1)-hydroxylase) with those of P-450 (testosterone 16 alpha-hydroxylase) produces a new stereospecific hydroxylase activity.

cDNA for chimeric P-450 consisting of the amino-terminal 462 residues of P-450 (laurate (omega-1)-hydroxylase) and the remaining 28 residues of P-450 (testosterone 16 alpha-hydroxylase) was constructed and expressed in yeast cells. The resulting chimera could catalyze laurate (omega-1)-hydroxylation and benzphetamine N-demethylation at much higher rates than the parental P-450s, but exhibited the same specificity towards fatty acid substrates as the wild-type laurate hydroxylase. When testosterone was examined as a substrate, the 16 beta-hydroxylated product, which cannot be formed by either of the parental P-450s, was detected, suggesting that the laurate hydroxylase contains a structure that is capable of binding testosterone at a proper orientation so that it can be hydroxylated at the 16 beta position.

Amino Acid Sequence↗

PubMed1990

Involvement of descending monoaminergic systems in the transmission of dental pain in the trigeminal nucleus caudalis of the rabbit.

Perfusates were taken from the superficial layers of the subnucleus caudalis of the trigeminal sensory nuclear complex (SpVc), the first relay station of dental pain, with a push-pull cannula system and were assayed for endogenous serotonin (5-HT) and catecholamines by high-pressure liquid chromatography with an electrochemical detection. Spontaneous release of 5-HT and epinephrine was observed, while that of norepinephrine was not. Tooth pulp stimulation (ST) tended to increase the level of 5-HT in the perfusates. Pretreatment with morphine at a dose of 10 mg/kg (i.v.) significantly enhanced the release of 5-HT. However, there was no significant difference in morphine effect on the 5-HT level between stimulated and non-stimulated animals. Systemic administration of morphine (10 mg/kg i.v.) completely inhibited the release of immunoreactive substance P from the superficial layers of SpVc evoked by ST, and this inhibition was antagonized by local application of methysergide (10(-4) M). These results suggest that in the superficial layers of SpVc, morphine may primarily activate the descending 5-HT pathway which serves to modulate dental pain transmission.

Animals↗

PubMed1990

Richter syndrome with two B cell clones possessing different surface immunoglobulins and immunoglobulin gene rearrangements.

A patient with two populations of B cell malignancy in the bone marrow is reported. One population consisted of mature small lymphocytes, expressing surface IgM + D, lambda and proliferating very slowly. The other population consisted of abnormal large lymphoid cells, expressing surface IgM, K and proliferating actively. We considered the former as chronic lymphocytic leukemia cells and the latter as malignant lymphoma cells. Therefore, this case was considered as Richter syndrome. The analysis of immunoglobulin heavy chain gene rearrangement showed the different patterns between the two populations. It suggested that the two populations arose from the different origins. We discussed the genetic relationship between the two clones of Richter syndrome referring to other reported cases.

Aged↗

PubMed1990

Quantitative bone histomorphometry and circulating T lymphocyte subsets in postmenopausal osteoporosis.

To explore the influence of the immune system on the development of osteoporosis, 19 untreated postmenopausal women with osteoporosis were studied by means of quantitative histomorphometry of the ilium and an analysis of T lymphocyte subsets in the peripheral blood. Osteoporotic women had lower OKT3+ and OKT8+ counts and a higher OKT4+/OKT8+ ratio than nonosteoporotic control subjects. Linear regression analyses disclosed that the age of subjects correlated with bone mineral density (BMD; r = -0.634, p less than 0.01) and some of the histomorphometric parameters for bone formation (r = -0.694 to -0.467, p less than 0.01-0.05). The number of OKT4+ cells showed weak but significant negative correlation with the parameters for bone resorption (r = -0.549 to -0.462, p less than 0.05). In a multiple regression analysis, the advanced age, the increase in OKT3+, and the decrease in OKT4+ and OKT8+ counts were shown to be significant predictors for the decrease in BMD (R = 0.882, p less than 0.01). According to the regression formula obtained from the analysis, the parameters for bone formation were related only to the age of subjects whereas those for bone resorption were tightly associated with the number of OKT4+ and OKT8+ cells but not with the age of subjects. These results indicated that, in addition to the age factor, abnormalities of the peripheral T lymphocyte subsets, especially those of OKT4+ and OKT8+ cells, are closely associated with the decrease in bone mass in postmenopausal osteoporosis, supporting the causal relationship between T lymphocyte functions and the development of postmenopausal osteoporosis.

Aged↗

PubMed1990

Removal of famotidine by haemodialysis in elderly anuric patients.

The effect of haemodialysis on the pharmacokinetics of oral famotidine has been studied in five elderly anuric patients. Famotidine 20 mg was administered in a cross-over design to patients on and not on haemodialysis. The elimination rate constant of haemodialysis (k) was 4.6-fold larger than the systemic elimination rate constant (ke). Although the mean maximum serum concentration of famotidine during haemodialysis (141.5 ng.ml-1) was not significantly lower than that without haemodialysis (195.6 ng.ml-1), the AUC up to 5 h during haemodialysis was significantly decreased to 58.1% of the value without it. The data suggest that famotidine is dialysable by haemodialysis.

Aged↗

PubMed1990

Elevation of the activities of glycosyl transferases involved in polylactosaminoglycan biosynthesis in autoimmune MRL lpr/lpr mouse T cells.

Lymph node (LN) T cells from autoimmune MRL/MpJ-lpr/lpr (lpr) mice and control MRL/MpJ-(+)/+ (+/+) mice were compared as to glycosyl transferase activities involved in the biosynthesis of polylactosaminoglycans. The N-acetylglucosaminyl transferase (GlcNAc transferase) activity responsible for the extension of polylactosaminoglycans was assayed. The reaction products with this GlcNAc transferase were characterized by sequential glycosidase treatment and methylation analysis, and the enzyme was found to be classifiable as an UDP-GlcNAc:N-acetyllactosamine beta 1-3 GlcNAc transferase (polylactosamine extension enzyme). The activity of this GlcNAc transferase in T cells from enlarged LN of lpr mice was 3-6 times higher than that in T cells from +/+ mice. On the other hand, activated T cells from +/+ mice only showed about a 2-fold increase in the activity of the transferase, compared with that in resting T cells. B cells from +/+ mice also showed a significantly higher activity of the transferase than +/+ T cells, the enzyme activity being comparable to or slightly lower than that in lpr T cells. Furthermore, when the reaction mixture contained both UDP-GlcNAc and UDP-Gal as donors, extension of the Gal-GlcNAc residue was observed. These results indicated the biosynthetic basis for the abundance of polylactosaminoglycans in lpr T cells and normal B cells. We also found that lpr T cells exhibited significant UDP-GlcNAc:asialo-bovine submaxillary mucin GlcNAc transferase activity. Only weak activity of this enzyme was detected in +/+ resting and activated T cells, and B cells. This enzyme activity suggested the potential for polylactosaminoglycan formation on the mucin-type sugar chains on the surface of lpr T cells.

Amino Sugars↗

PubMed1990

In vivo localization of antitumor lymphocytes separated with Dolichos biflorus lectin.

We examined the in vivo localization of Con A sup-cultured murine splenocytes separated with Dolichos biflorus agglutin (DBA) to elucidate the mechanism underlying the high antitumor efficacy of cells which are not agglutinable with DBA (DBA- cells). First, 51Cr-labeled DBA-separated cells were injected intravenously (i.v.) into mice and then the tissues were collected for gamma counting. DBA- cells showed significant localization in the spleen, compared with DBA+ cells. This was further confirmed by injecting Thy1.2-positive DBA- cells into Thy1.1 congenic mice. Furthermore, after [3H]TdR-labeled DBA-separated cells had been injected i.v., the spleens of the recipients were fixed, sectioned and processed for autoradiography to determine in which region of the spleen the labeled cells had accumulated. We found that DBA- cells were especially concentrated in the white pulp of the spleen, where lymphocytes are localized before being recirculated. These results suggest that DBA- cells exert strong antitumor activity in vivo partly due to their localization in the spleen and partly to the high incidence of active recirculation.

Animals↗

PubMed1990

Anti-tumour efficacy of mouse spleen cells separated with Dolichos biflorus lectin (DBA) in experimental pulmonary metastasis of B16 melanoma cells.

Anti-tumour effector cells were generated through 4 days culture of normal C57BL/6 splenocytes in a medium containing concanavalin A supernatant and then fractionated with Dolichos biflorus lectin (DBA) into DBA+ (agglutinable with DBA) and DBA- (non-agglutinable with DBA) cells. The DBA- cells, infused intravenously into mice together with B16 melanoma cells, or adoptively transferred into mice 3 days after the injection of B16 cells, caused a marked decrease in the number of lung nodules, while the DBA+ cells exerted no effect. On the other hand, the DBA+ cells exhibited higher cytolytic activity in vitro than the DBA- cells in short-term 51Cr-release assays. Then, we analysed the mechanism of the strong anti-tumour activity of DBA- cells in vivo. We found that DBA- cells showed higher response to recombinant interleukin-2 (rIL-2) than DBA+ cells and proliferated very well with a small amount of IL-2. In addition, DBA- cells adhered more strongly to lung endothelial cells than DBA+ cells in response to rIL-1 or rTNF. Furthermore, DBA- cells produced larger amounts of macrophage activating factor (MAF) including IFN-gamma when cultured with B16 melanoma. Taken together, our results show that DBA- cells are effective in reducing experimental pulmonary metastases not only by the direct lytic activity but also by the indirect killing activity through the activated macrophage.

Animals↗

PubMed1990

Odor types determined by the major histocompatibility complex in germfree mice.

The major histocompatibility complex (MHC) is the prime but not exclusive determinant of genetically specific constitutive body odors, termed odor types, represented strongly in urine of the mouse. Perception of MHC-determined odor types influences reproductive behavior in the contexts of mate choice and maintenance of early pregnancy, tending to favor the propagation of one MHC type over another. How MHC genotype determines MHC odor type is unknown. One possible explanation is that differential odorants are generated by populations of commensal microorganisms whose composition is somehow geared to MHC diversity. This hypothesis was tested in the Y-maze system in which mice are trained to distinguish the urinary odors of MHC-congenic mice. First, it was shown that mice could readily be trained to distinguish the urines of germfree MHC-congenic mice. Second, it was shown that mice trained to distinguish the urines of conventionally maintained MHC-congenic mice could as readily distinguish the urines of germfree MHC-congenic mice. These results imply that MHC-determined odor types do not depend on odorants generated by microorganisms.

Animals↗

PubMed1990

A homing receptor-IgG chimera as a probe for adhesive ligands of lymph node high endothelial venules.

The binding of lymphocytes to high endothelial venules (HEV) within peripheral lymph nodes (pln) is thought to be mediated by a lectinlike adhesion molecule termed the pln homing receptor (pln HR). The cloning and sequencing of cDNAs encoding both murine and human pln HR revealed that these adhesion molecules contain protein motifs that are homologous to C-type or calcium dependent lectin domains as well as to epidermal growth factor (egf) and complement-regulatory protein domains. We have produced a novel, antibody-like form of the murine HR by joining the extracellular region of the receptor to a human IgG heavy chain. This antibody-like molecule is capable of recognizing carbohydrates, blocking the binding of lymphocytes to pln HEV, and serving as a histochemical reagent for the staining of pln HEV. This murine HR-IgG chimera should prove useful in analyzing the distribution of the HR ligand(s) in normal as well as in inflammatory states.

Animals↗

PubMed1990

Direct demonstration of the lectin activity of gp90MEL, a lymphocyte homing receptor.

Considerable evidence implicates gp90MEL as a lymphocyte homing receptor mediating lymphocyte attachment to high endothelial venules of lymph nodes in mouse. The protein appears to function as a calcium-dependent, lectin-like receptor as inferred primarily by the ability of specific carbohydrates to block its function and by the presence of a calcium-type lectin domain in its primary sequence. An ELISA assay is described which provides the first demonstration that the isolated protein has lectin activity and allows a further definition of its carbohydrate specificity. In addition to the monosaccharides mannose-6-phosphate and fructose-1-phosphate, ligand activity is shown for the sulfated glycolipid, sulfatide, and for two sulfated fucose-containing polysaccharides (fucoidin and egg jelly coat) from nonmammalian sources.

Animals↗

PubMed1990

Determination of clinical accuracy and nocturnal blood pressure pattern by new portable device for monitoring indirect ambulatory blood pressure.

The accuracy and clinical application of a new portable device for measuring ambulatory blood pressure (BP) (ABPM 630, Nippon Colin, Nagoya, Japan) were assessed. The device uses a conventional arm cuff inflated by CO2 gas from a compact cartridge and is based on a cuff-oscillometric as well as a Korotkoff sound (microphone) technique. Blood pressure values obtained by ABPM 630 were compared with those measured by the auscultatory method. With the microphone method the mean differences from the auscultatory method were -0.28 +/- 6.15 mm Hg (mean +/- SD) for SBP and 0.96 +/- 6.28 mm Hg for DBP (n = 256), while for the cuff-oscillometric method the mean differences were -1.77 +/- 6.07 mm Hg for SBP and 3.06 +/- 6.87 mm Hg for DBP (n = 297). There was a highly significant correlation between BP values measured by the auscultatory method and ABPM 630. In 40 untreated subjects, 24 h BP was monitored simultaneously with the ABPM 630 and with a finger volume-oscillometric device (UBP-100, UEDA, Tokyo, Japan). The daytime average of SBP with the former (126 +/- 11.6 mm Hg) was almost the same as that with the latter (123 +/- 16.0 mm Hg), while the nighttime average in the former (117 +/- 9.7 mm Hg) was significantly higher than that in the latter (108 +/- 14.1 mm Hg, P less than .01). Only 4 out of 40 subjects experienced no sleep disturbance from the arm-cuff inflation. Five of the 40 subjects complained that their sleep was frequently interrupted by the arm-cuff inflation.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗

PubMed1990

Myocardial perfusion after aortic implantation for anomalous origin of the left coronary artery from the pulmonary artery.

Postoperative myocardial perfusion and function were evaluated using thallium-201 myocardial imaging and technetium-99m cardiac pool imaging in five patients with an anomalous left coronary artery arising from the pulmonary artery. The patients underwent reimplantation of the left coronary artery at an age ranging from 10 months to 13 years. Postoperative electrocardiographic and radionuclide studies were performed both at rest and during stress 1 to 4 years after the operation. Electrocardiograms which were abnormal preoperatively returned to normal after surgery except that the T wave in lead aVL remained negative. Postoperatively, left ventricular ejection fraction measured by technetium-99m cardiac pool imaging was normal in all patients. Postoperative thallium-201 myocardial imaging, however, showed a perfusion defect with incomplete redistribution at the high-lateral or antero-lateral segment in all patients after a stress test. These data suggest that although myocardial ischaemic change decreases and global cardiac function improves after establishment of a dual coronary artery system, severe myocardial damage remains at the high-lateral or antero-lateral segment.

Adolescent↗

PubMed1990

Characterization of rabbit liver P450IIE1 synthesized in transformed yeast cells.

cDNA for chimeric protein, P450(3P4), consisting of the amino-terminal 43 residues (the membrane-anchor region) of rabbit P450IIC14 and the remaining 447 residues of rabbit P450IIE1 was constructed, then cloned into expression vector pAAH5, and expressed in Saccharomyces cerevisiae AH22 cells under the control of yeast ADH1 promoter. P450(3P4) thus synthesized in the transformed yeast cells was partially purified, and its spectral and catalytic properties were examined. In the oxidized state P450(3P4) exhibited a high-spin type absorption spectrum even in the absence of a substrate. The reduced CO complex of the P450 showed a Soret absorption maximum at 452 nm. P450(3P4) catalyzed aniline p-hydroxylation, N-nitrosodimethylamine demethylation, benzphetamine N-demethylation, and laurate and caprate (omega-1)-hydroxylation in the reconstituted system containing the P450 and NADPH-P450 reductase. These results indicate that P450(3P4) preparation obtained from the transformed yeast cells has spectral and catalytic characteristics identical with those of P450IIE1 purified from rabbit liver microsomes, confirming the substrate specificity reported of P450IIE1.

Animals↗

PubMed1990

Effects of interleukin-6 and granulocyte colony-stimulating factor on the proliferation of leukemic blast progenitors from acute myeloblastic leukemia patients.

The effects of recombinant human interleukin-6 (rh IL-6), which has homology with rh granulocyte colony-stimulating factor (rh G-CSF) at the amino acid sequence level, and rh G-CSF on normal human bone marrow cells, fresh leukemic blast progenitors from 16 acute myeloblastic leukemia (AML) patients, and G-CSF-dependent human AML cell line (OCI/AML 1a) were investigated. rh G-CSF stimulated the proliferation of leukemic blast progenitors from 13 out of 16 AML patients tested. rh IL-6 stimulated the proliferation of blasts from eight AML patients and enhanced the G-CSF-dependent proliferation of the fresh AML blasts from two out of eight patients tested. On the other hand, rh IL-6 suppressed the blast colony formation from two AML patients and OCI/AML 1a cells and also reduced the G-CSF-dependent proliferation of the blast progenitors from one of the two patients and the cell line, rh IL-6 had no effect on the colony formation of normal granulocyte-macrophage colony-forming units (CFU-GM) with or without rh G-CSF. Differentiation-induction by rh IL-6 was not observed in the fresh AML blasts but was observed in OCI/AML 1a. The effect of IL-6 on the blast colony formation and G-CSF-dependent blast cell growth was complicated and heterogenous among the AML cases; IL-6 stimulated blast colony formation in some cases and suppressed it in others. The heterogeneity of the response was supposed to be derived from the heterogeneity of the characteristics of AML cells. Although G-CSF simply stimulated the blast colony formation, IL-6 had a bimodulatory effect on the proliferation of leukemic blast progenitors from AML patients. IL-6 might be involved in the regulation of the proliferation of AML cells in vivo as well as in vitro.

Adolescent↗

PubMed1990

Proliferation kinetics of rat Kupffer cells after partial hepatectomy. Immunohistochemical and ultrastructural analysis.

In an effort to settle the conflicting views on the proliferation kinetics of Kupffer cells (Kc), we performed 2/3 partial hepatectomy on rats injected with Pelikan ink. Using an anti-rat macrophage monoclonal antibody, ED 2, we evaluated the numerical changes in total, carbon-positive ED 2+ cells and carbon-negative ED 2+ cells in the portal and central area. We also analyzed the ultrastructure and peroxidase cytochemistry of various types of cells observed during regeneration. The total numbers of ED 2+ cells in the remaining liver increased rapidly from day 2 to 5, and the number of dividing ED 2+ cells reached a maximum on day 2. Thus, the numerical increase in ED 2+ cells corresponded to the division phase. In contrast, the carbon-labeling experiment showed a continuous increase of carbon-negative ED 2+ cells from day 2 to 7. In the central area where division was less frequent, the proportion of carbon-positive cells decreased markedly to 50% on day 7, as against 97% in control rats. These findings suggest the possibility of an influx of carbon-negative Kc in addition to cell division. Ultrastructurally, the presence of carbon-negative "small Kc" and "immature Kc" with morphological features different from those of carbon-positive Kc was demonstrated. Such carbon-negative Kc with a high nucleus-to-cytoplasm ratio and rather few phagosomes, were not observed in control rats. Furthermore, we demonstrated two types of possible precursor cell, i.e. "transitional" forms between monocytes and Kc, and "immature macrophages". The former showed peroxidase activity in some lysosomes as well as in the rough endoplasmic reticulum and nuclear envelope. Our result indicated that the proliferation kinetics of Kc depend upon both local proliferation and influx.

Animals↗

PubMed1990

Release of calcitonin gene-related peptide-like immunoreactive substance from neuromuscular junction by nerve excitation and its action on striated muscle.

In a rat phrenic nerve-hemidiaphragm preparation, calcitonin gene-related peptide (CGRP) increased the twitch contraction induced by nerve or transmural stimulation dose dependently. Either electrical or high K+ stimulation of the phrenic nerve caused release of a CGRP-like immunoreactive substance (CGRP-LIS) in a Ca2(+)-dependent manner. Electrical stimulation of the phrenic nerve also increased the cyclic AMP content in diaphragm. This increase was not observed in Ca2(+)-free medium and was blocked by antiserum against CGRP. These results indicate that excitation of the motor nerve causes release of CGRP-LIS at nerve terminals and that the released CGRP-LIS increases the cyclic AMP content of skeletal muscles and potentiates twitch contraction.

Animals↗

PubMed1990

Cytokines and osteoporosis.

Bone remodeling is controlled by systemic factors such as parathyroid hormone (PTH), calcitonin (CT), and 1,25(OH)2 vitamin D and by local factors including cytokines and growth factors such as IL-1, IL-2, TNF alpha, TGF beta, IFN alpha, and IFN gamma. Derangement of such control mechanisms leading to an imbalance between osteoclastic bone resorption and osteoblastic bone formation could cause osteoporosis. Conditions associated with immune dysfunction such as aging, corticosteroid therapy, and rheumatoid arthritis are associated with osteoporosis, which is also more common in females than in males, like most of the autoimmune-collagen diseases. Peripheral lymphocyte subsets CD4/CD8 were higher in patients with senile osteoporosis than in the age-matched controls, and returned to normal after 1 month of 1 alpha(OH)vitamin D3 treatment. On multiple regression analysis of histomorphometric data and lymphocyte subsets, a negative correlation was found between CD4 lymphocytes and bone resorption. High CD4 is thus associated with a low level of osteoclastic bone resorption or low turnover osteoporosis. Plasma interferon reflecting macrophage function decreased with advance in age and increased in response to 1 alpha(OH)D3 treatment. As one of the immunoregulators, vitamin D tends to stimulate the macrophage-natural killer system and suppress the lymphocyte system, stimulating TGF beta and TNF alpha activity. Senile osteoporosis of low turnover thus appears to be associated with vitamin D deficiency, low macrophage function, high CD4 lymphocyte proportion, low IL-1 and high IL-2 activity, low IFN alpha and high IFN gamma activity, and low TGF beta and TNF alpha activity. Treatment with vitamin D derivatives tends to reverse these changes.

Aging↗