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Biomedical subjects

M Takata

Publications and source records attributed to M Takata.

At least 199 records · Page 11Linked to original sources

Subcorneal pustular dermatosis associated with IgA myeloma and intraepidermal IgA deposits.

We report a 59-year-old woman who had subcorneal pustular dermatosis and IgA-kappa myeloma. Immunofluorescence tests showed intercellular IgA-kappa deposits in the upper portion of the lesional epidermis and circulating IgA-kappa anti-intercellular autoantibodies in a titer of 1:40. A combination chemotherapy for myeloma induced dramatic improvement of the skin lesions in accordance with a marked decrease in serum IgA levels as well as the disappearance of circulating anti-intercellular IgA autoantibodies, suggesting a pathogenetic link between skin lesions and IgA-kappa paraprotein produced by myeloma cells.

Autoantibodies↗

Inflammatory chemical mediators during conventional ventilation and during high frequency oscillatory ventilation.

Inflammatory chemical mediators, platelet-activating factor (PAF), thromboxane (TX) B2, and 6-keto-prostaglandin (PG)F1 alpha, were extracted from lung lavage fluid after conventional mechanical ventilation (CMV) and high frequency oscillatory ventilation (HFOV) to clarify the relation between mode of ventilation and lung injury in surfactant-depleted rabbit lungs. Anesthetized adult rabbits were tracheostomized, and surfactant depletion was induced by repeated saline lavage. Lung lavage for measurement of mediators was performed after 4 h of CMV at an FIO2 of 1.0 and a mean airway pressure of 15 cm H2O or HFOV (15 Hz) at an FIO2 of 1.0 or 0.21 and a mean airway pressure of 15 cm H2O. The number of total cells and polymorphonuclear leukocytes (PMN) and the levels of PAF, TXB2, and 6-keto-PGF1 alpha were measured by radioimmunoassay. Total respiratory compliance (Crs) was measured by the passive flow-volume curve method. The numbers of PMN, and the levels of PAF and TXB2 in lung lavage fluid were significantly greater during CMV than during HFOV. HFOV resulted in decreased production of PAF and TXB2 in a surfactant-depleted rabbit lung. Crs was significantly less during CMV than during HFOV. These results suggest that HFOV could prevent the release of such inflammatory chemical mediators and result in less lung injury than CMV.

6-Ketoprostaglandin F1 alpha↗

Diagnostic value of captopril test in hypertensive patients with renal artery stenosis.

To examine the utility of the single-dose captopril test in detecting renovascular hypertension (RVHT), the authors measured peripheral plasma renin activity (PRA), before and thirty and sixty minutes after an oral dose of captopril (25 mg), in 28 patients with RVHT and 22 patients with high-renin essential hypertension (EHT) without renal artery stenosis who were consuming 8 grams of sodium chloride per day. There was considerable overlap of individual values in basal PRA between the two groups. Sixty minutes after captopril, PRA was higher in RVHT than in EHT patients (74.8 +/- 63.9 versus 15.1 +/- 11.9 ng/mL/hr, P < 0.01). With the cutoff point set at 16 ng/mL/hr, RVHT was detected with a sensitivity of 96% and a specificity of 77%. The discriminating power was also superior to that based on blood pressure response to angiotensin II analogue under sodium depletion, rapid-sequence intravenous pyelography, or renography. These results show that captopril-stimulated peripheral PRA is an adequate screening tool for detecting RVHT in a population with high-renin hypertension.

Adult↗

Pressure-volume relationships of the respiratory system in normal cats.

We studied the pressure-volume (PV) relationships of the total respiratory system, lung and chest wall in 8 anesthetized and paralyzed normal adult cats. The PV relationships of the total respiratory system had a sigmoid shape with a relatively linear portion with an alveolar pressure between 0 to +15 cmH2O. The relative impact of the lung and chest wall to the total elastic recoil forces of the respiratory system was approximately equal within a physiological pressure range. The results suggest that measurements of PV relationships of the respiratory system may offer a physiologic basis for accurate interpretation of pulmonary functions, leading to a better therapeutic strategy in animals with lung diseases.

Animals↗

Analysis of longitudinal distribution of pulmonary vascular resistance by use of a five element lumped model.

To analyze longitudinal distribution of pulmonary vascular resistance, we proposed a five element lumped model which partitioned pulmonary circulation into pulmonary arterial, middle and pulmonary venous segment. The validity and anatomical correlation of the model were tested in an isolated, perfused, canine lung lobe preparation with inflow/outflow occlusion techniques. With arterial occlusion, pulmonary arterial pressure fell rapidly and then exponentially. With venous occlusion, pulmonary venous pressure rose suddenly and then exponentially. Theoretical pressure profiles produced by computer simulation of the model well approximated the general characteristics of the experimental traces. Serotonin increased the pressure gradient across the pulmonary arterial segment (delta Pa), whereas histamine increased the gradient across the pulmonary venous segment (delta Pv). Neither drug altered the gradient across the middle segment (delta Pm). The results suggest that the lumped model is a useful concept to understand the longitudinal distribution of pulmonary vascular resistance, and that delta Pa, delta Pm and delta Pv reflect the resistance distribution of anatomical pulmonary arteries, alveolar vessels and pulmonary veins, respectively.

Animals↗

[VCAP chemotherapy combined with interferon-alpha (HLBI) for elderly multiple myeloma].

VCAP chemotherapy combined with natural interferon-alpha (HBLI) was performed on elderly patients over 65 year with multiple myeloma (MM), and its clinical effects were compared with those of VCAP chemotherapy without HLBI on elderly MM and also with those of HLBI-VCAP and VCAP combination therapy on non-elderly MM. Sixteen elderly and 21 non-elderly patients received HLBI-VCAP combination therapy, whereas 12 elderly and 21 non-elderly patients were treated with VCAP chemotherapy alone. The remission rate (CR+PR) was 81% for the elderly HLBI-VCAP group, 58% for the elderly VCAP group, 90% for the non-elderly HLBI-VCAP group, and 76% for the non-elderly VCAP group. While the median survival time was 54 months for the elderly HLBI-VCAP group and 13.5 months for the elderly VCAP group, it was 70 months for non-elderly HLBI-VCAP group and 34.5 months for the non-elderly VCAP group. The survival time in the elderly HLBI-VCAP group was significantly longer than that in the elderly VCAP group. Therefore, improvement of survival in cases treated by interferon was much better in the elderly group than in the non-elderly group. These results indicate that HLBI-VCAP combination therapy is beneficial for the treatment of elderly MM.

Aged↗

Cl- channel as a cholinergic ACh receptor responsible for generation of inhibitory junction potential in Aplysia buccal muscle cells.

Action potentials in Aplysia MA1 neurons are known to produce inhibitory junction potentials (IJPs) in muscle cells in a specific portion (mm block) of the buccal musculature. These IJPs are reversibly blocked by curare (d-TC), suggesting that the transmitter is acetylcholine (ACh) and the receptor is a cholinergic ACh receptor. Muscle fibres were enzymatically dissociated from the mm portion, and whole cell patch clamp was performed onto those fibres to study the ionic mechanism associated with the ACh reception. The results revealed that the ACh receptor is associated with a Cl- channel.

Acetylcholine↗

[Relationship between prognosis of multiple myeloma and response to VCAP therapy].

We investigated the relationship between response in M-protein to VCAP therapy and survival duration in 50 multiple myeloma (MM) patients who survived for at least 6 months. The relationship between improvement of hemoglobin level as a response of VCAP therapy and survival duration was also assessed. The survival time in patients whose M-protein was reduced by 50% or more within 6 months after therapy was shorter than that in patients in whom the reduction of > or = 50% or more was obtained in more than 6 months. Patients with a hemoglobin level of 10 g/dl or higher before therapy survived significantly longer than those with a hemoglobin level of less than 10 g/dl. Among the patients with a hemoglobin level of less than 10 g/dl, patients in whom the hemoglobin level improved to 10 g/dl or higher survived for significantly longer duration than patients without improvement (p < 0.01). Patients in whom the hemoglobin level improved after more than 6 months survived form significantly longer duration than patients in whom hemoglobin level improved within 6 months. Therefore, it was considered that it was difficult to predict prognosis from the rate of decrease in M-protein in the early stage of treatment.

Aged↗

Analysis of T-cell receptor alpha beta chains of CD8+ suppressor T cells induced by tolerogenic conjugates of antigen and monomethoxypolyethylene glycol. Involvement of TCR alpha-CDR3 domain in immunosuppression.

A number of investigators have demonstrated that there exists a relationship between Ag receptors of Ts cells (TCR) and their soluble suppressor factors. With a view to elucidating this relationship, the primary structures of receptors of Ts cells, induced in mice by tolerogenic conjugates of Ag and monomethoxypolyethylene glycol, were characterized in this study. The cDNA encoding the alpha and beta chains of TCR of cloned Ts cells specific for (i) OVA and (ii) human monoclonal (myeloma) IgG (HIgG) were produced by polymerase chain reaction. From the analysis of the V alpha genes of TCR of Ts cells it was deduced that these receptors utilized a new member of the V alpha 15 gene family, which was productively joined to the J alpha genes that differed for each of the Ts cells of the two distinct specificities. Similarly, sequence analysis of the beta chain cDNA of the two Ts cell clones revealed that both clones utilized the V beta 8.2 gene, and that their J beta gene differed from each other. It is inferred that the Ts cells generated in response to the different tolerogenic Ag(mPEG)n conjugates belonged to a subset of T cells utilizing similar TCR alpha beta chains and differed only in their J alpha/J beta regions. Most importantly, pretreatment of mice with a mixture of pentadecapeptides comprising the TCR alpha chain of the OVA-Ts cells, down-regulated the immune response specific to OVA, but not to HIgG. Moreover, injection of mice with a pentadecapeptide corresponding to the CDR3 region of the TCR alpha chain of either OVA-Ts or HIgG-Ts suppressed specifically the Ab response to OVA or HIgG, respectively. On the basis of all these results, it is concluded that the CDR3 of the TCR-alpha chain of Ts cells plays a pivotal role in the Ts network underlying the specific down-regulation of the immune responses induced by tolerogenic Ag(mPEG)n conjugates.

Amino Acid Sequence↗

New flow cytometric method for surface phenotyping basophils from peripheral blood.

To clarify the role of basophils in the pathogenesis of allergic disease, we developed a new method for performing surface phenotyping of these cells in centrifugation-enriched mononuclear cell fraction. This method identified basophils on the basic of a negative reactivity with mixed FITC-conjugated monoclonal anti-bodies (mAbs) (anti-CD2, -CD14, -CD16, and -CD19) with analysis performed by flow cytometry. The validity of this approach was confirmed by sorting experiments. Various PE-conjugated mAbs were also used to examine binding to FITC-negative basophils. Basophils from asthmatic patients (n = 14) as well as from normal subjects (n = 6) were shown to express CDw32 (Fc gamma RII), CD25 (IL-2R), but not CD64 (Fc gamma RI). We also detected binding of IgG1 and IgG4 to basophils. This method of phenotyping was very rapid and simple. It thus appears to be useful in the study of allergic disease, as well as of the biology of the basophil.

Antibodies, Monoclonal↗

Antigen-specific suppressor factors of noncytotoxic CD8+ suppressor T cells downregulate antibody responses also to unrelated antigens when the latter are presented as covalently linked adducts with the specific antigen.

We had previously shown (i) that conjugates of a given antigen A (AgA) and monomethoxypolyethylene glycol (mPEG) induced AgA-specific tolerance in mice which was mediated by polyclonal CD8+ suppressor T (Ts) cells, as well as by soluble factor(s) of these cells (TsF), and (ii) that clones of nonhybridized CD8+ Ts cells could be derived from the above single cells, and monoclonal AgA-specific TsF could be released from these cloned cells. In the present study, we demonstrate that mice pretolerized by injection of AgA(mPEG)n are also unresponsive to an unrelated antigen B (AgB), or to its haptenated derivative AgB-Hpn, when AgB or AgB-Hpn is injected in the form of a covalent adduct with AgA, i.e., AgA-AgB or AgA-AgB-Hpn, but not when it is injected as a mixture with AgA; in this study human (myeloma) IgG (HIgG) served as AgA, and ovalbumin (OVA) or OVA-DNP3 served as AgB or AgB-Hpn. Moreover, this phenomenon was reproduced in vitro; i.e., Ts cells of mice tolerized with HIgG(mPEG)30, or the soluble monoclonal TsF of cloned Ts cells, exerted their associative suppressive effector function--in the obligatory presence of CD8+ T cells of syngeneic naive mice (Tn cells)--on antibody (Ab) formation to an Hp (DNP), when the Hp was present as a covalent adduct linked either directly to HIgG (e.g., HIgG-DNP7) or indirectly via OVA (as in HIgG-OVA-DNP3); however, no suppression of the anti-DNP Ab response was observed when OVA-DNP3 was present as a mixture with HIgG. Furthermore, it was established that the accessory cells involved in processing the specific Ag in the presence of the Ts cells were also downregulated, as reflected by their reduced capacity for presentation of the Ag to HIgG-specific helper T (Th) cells in proliferation assays. All these results demonstrate that (i) the phenomenon of linked immunological suppression may involve the downregulation of Th cells which recognize, concomitantly with the Ts cell, the appropriate epitopes of AgA and AgB on the same Ac cell, (ii) the downregulation of these Th cells may be a consequence of the downregulation of Ac cells by Ts cells interacting with the appropriate epitope(s) present on the Ac cells, and (iii) most remarkably the CD8+ Ts cells could be substituted by Tn cells "armed" with the specific monoclonal TsF.

Animals↗

Structure and chromosomal localization of the gene encoding the human myelin protein zero (MPZ).

We describe the cloning, characterization, and chromosomal mapping of the human myelin protein zero (MPZ) gene. The gene is about 7 kb long and consists of six exons corresponding to the functional domains. All exon-intron junction sequences conform to the GT/AG rule. The 5'-flanking region of the gene has a TA-rich element (TATA-like box), two CAAT boxes, and a single defined transcription initiation site detected by the primer extension method. The gene for human MPZ was assigned to chromosome 1q22-q23 by spot blot hybridization of flow-sorted human chromosomes and fluorescence in situ hybridization. The localization of the MPZ gene coincides with the locus for Charcot-Marie-Tooth disease type 1B, determined by linkage analysis.

Base Sequence↗

Flow velocity profile of the pulmonary artery measured by the continuous cardiac output monitoring catheter.

The KATS catheter (continuous arterial thermodeprivation system catheter) measures the blood flow velocity of the pulmonary artery (PA) by thermodeprivation which enables continuous determination of cardiac output. The accuracy of this system may depend on the degree of uniformity of flow velocity in the PA, because small movements of the catheter within the PA are inevitable with a beating heart. We evaluated the flow velocity profile of the PA in seven anaesthetized open-chest dogs to assess these potential errors. A custom-made stiff catheter, at the tip of which was incorporated the flow velocity sensor of the KATS catheter, was used to penetrate the main PA in the short axis direction (perpendicular to flow direction) or the long axis direction (along flow direction). The stiff catheter was moved in increments of 2.5 mm, and flow velocity was recorded. The wall-to-wall distance of the PA along each direction was divided into five sections (S1 to S5 for the short axis, and L1 to L5 for the long axis). Flow velocity data for each section were averaged and presented as relative values against the control mid-point velocity. Along the short axis, flow velocity was 0.41 +/- 0.20 (SD), 1.00 +/- 0.10, 1.03 +/- 0.10, 1.08 +/- 0.13 and 0.49 +/- 0.26 from S1 to S5, i.e., lower in S1 and S5 which were close to the vascular walls (P < 0.05) but uniform in other areas. Along the long axis, flow velocity was 0.28 +/- 0.28, 0.88 +/- 0.09, 0.94 +/- 0.08, 1.06 +/- 0.25 and 1.28 +/- 0.50 from L1 to L5.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunoelectron microscopy of acute graft versus host disease of the skin after allogeneic bone marrow transplantation.

AIMS: To clarify the pathological mechanisms of acute cutaneous graft versus host disease (GvHD) following allogeneic bone marrow transplantation. METHODS: Skin biopsy specimens from five patients were examined by immunoelectron microscopy. A panel of monoclonal antibodies against T cell and natural killer cell subpopulations was used, including anti-CD4, -CD8, -CD16b, -CD56, -CD57, and -TCR delta 1 antibodies. RESULTS: All the specimens contained CD8+ cells, CD4+ cells, and CD56+ cells infiltrating the epidermis. Cells stained with anti-CD16b, -CD57, or -TCR delta 1 were very sparse or absent. Most of the CD8+ cells in the epidermis displayed morphological features of activated cytotoxic T lymphocytes and apposition of such cells to degenerating keratinocytes was shown. CD4+ cells outnumbered CD8+ cells in the epidermis in all five cases. Noticeable intercellular as well as intracellular oedema of keratinocytes was observed at the site of prominent CD4+ cell infiltration, suggesting that these also have a role as actual effector cells by secreting cytotoxic cytokines. CD56+ cells infiltrating the epidermis did not exhibit the characteristic ultrastructural morphology of the natural killer cells thus far examined, and their lineage remained uncertain. CONCLUSIONS: These data provide direct evidence that CD8+ cytotoxic T cells attack keratinocytes, and further suggest that CD4+ cells as well as CD56+ cells participate in the cellular pathogenesis of acute cutaneous GvHD.

Adolescent↗

Effect of a novel immunosuppressant, FK506, on spontaneous lupus nephritis in MRL/MpJ-lpr/lpr mice.

We evaluated the effect of the novel immunosuppressive agent, FK506, which is known to inhibit T cell immunity, on the development of lupus nephritis in MRL/MpJ-lpr/lpr (MRL/l) mice. FK506 was administered subcutaneously (1 mg/kg body weight) from 12 to 20 weeks of age in 13 MRL/l mice with spontaneous lupus nephritis. Nine animals receiving no treatment were used as the control. FK506 significantly reduced the development of proteinuria, lowered the level of BUN, and suppressed the elevation of serum anti-dsDNA antibodies. Histopathological study showed that FK506 significantly inhibited the progression of glomerular hypercellularity and crescent formation. Glomerular deposition of C3 was significantly reduced in the FK506-treated mice compared to the nontreated controls. These findings suggest that FK506 may protect against progression of lupus nephritis in MRL/l mice, an animal model of systemic lupus erythematosus.

Animals↗

[A case of elderly Hashimoto disease presenting malignant lymphoma, gastric cancer and colon cancer].

An 87-year-old woman, who had been suffering from hypothyroidism and had been treated as an outpatient at our department since 1982, noticed left cervical swelling toward the end of November 1992. Because ultrasonic examination revealed a mass in her thyroid gland, she was admitted for a closer examination and additional treatment. Biopsy of thyroid gland revealed non-Hodgkin's lymphoma (NHL; the diffuse small cell type, B-cell origin). A part from the swelling of thyroid gland and the left cervical lymph node, performance of various examinations did not detected any other NHL lesions. Therefore, it was classified as stage II NHL according to the Ann Arbor classification. Laboratory data on admission were as follows; WBC 4,400/microliters, Hb 13.6 g/dl, platelet count 10.1 x 10(4)/microliters, GOT 51 IU/l, GPT 31 IU/l, TSH 1.17, free-T4 1.03, free-T3 2.04, and microsome test 1,600 x. Those data indicated marked hypothyroidism. In addition, stage IIa and IIc gastric cancers were detected by the examination with gastric endoscopy performed for stage classification. Both were adenocarcinomas. Because polyps were found in her sigmoid colon with colonoscopy, polypectomy was performed. The polyps were diagnose histologically as moderately differentiated adenocarcinoma. On July 20, COP-BLAM therapy was started (CPM 600 mg div, VCR 1.2 mg iv, ADR 30 mg iv on day 1, PDN 40 mg p.o and PCZ 100 mg p.o. on days 1-10, BLM 7.5 mg div on day 14). Subsequently, the left cervical lymph node swelling disappeared, and shrinkage of the mass in the thyroid gland was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Glomerulosclerosis in the rat induced by repeated immune-mediated mesangial cell injury.

Glomerulosclerosis is a common feature of progressive glomerular injury. We investigated whether experimental glomerulosclerosis could be induced by repeated immunologic injury to mesangial cells. Chronic mesangial proliferative glomerulonephritis (GN) was induced by repeated injections of polyclonal antibody directed against the Thy 1 antigen present on the mesangial cell membrane. An intravenous injection of anti-Thy 1 serum (ATS) was given weekly to 18 male Wistar rats, which were sacrificed at weeks 2, 4 and 6 after induction of GN. Blood urea nitrogen and serum creatinine were significantly elevated in rats with anti-Thy 1 nephritis at weeks 4 and 6 compared to normal rats. Progressive expansion of the mesangial matrix with diffuse sclerosis was observed at weeks 4 and 6 by silver methenamine staining. Ultrastructurally there was a prominent rough endoplasmic reticulum in the mesangial cells and collagenous fibrils in an expanded mesangial matrix. Immunohistochemical staining revealed a marked increase in type IV collagen and laminin in the mesangium at weeks 4 and 6. Thus, repeated immunologic injury restricted to the mesangium may result in the accumulation of extracellular matrix and the development of glomerulosclerosis. These studies emphasize the importance of the mesangial cell in progressive glomerular injury.

Animals↗