Biomedical subjects

M Takata

Publications and source records attributed to M Takata.

At least 181 records · Page 10Linked to original sources

PubMed1995

Spontaneous disappearance of intraepidermal type VII collagen in a patient with dystrophic epidermolysis bullosa.

Recently, a peculiar self-healing neonatal blistering disease has been reported, which is characterized by perinuclear stellate inclusions within basilar keratinocytes, representing abnormal retention of type VII collagen. We report a Japanese patient with this condition, in whom we studied the expression of a variety of basement membrane zone (BMZ)-related antigens. Skin biopsy specimens at 3 days of age showed abundant accumulation of both the NC-1 domain and the collagenous part of type VII collagen within the basal and suprabasal keratinocytes, in addition to patchy and weak staining along the BMZ. In contrast, at 4 years of age, when the disease activity was markedly attenuated, a second biopsy showed complete linear staining of type VII collagen along the BMZ, with no detectable intracytoplasmic deposits. Expression of other BMZ-related antigens, including laminin 5, alpha 6 and beta 4 integrins, bullous pemphigoid antigens 1 and 2, and type IV collagen, was normal in both the biopsy specimens. Our observations further confirm that the perinuclear stellate bodies seen in this peculiar condition are composed of both collagenous and non-collagenous domains of type VII collagen retained within the epidermis, and that these bodies disappear when the disease activity remits.

Basement Membrane↗

PubMed1995

Mechanical abdomino/heart/lung interaction.

It is generally assumed that inspiration will enhance both superior and inferior vena cava (SVC and IVC) blood flows due to the decrease in right atrial pressure produced by the fall in intrathoracic pressure. However, inspiration can also increase abdominal pressure due to the descent of the diaphragm. Using a model of abdominal vascular zone conditions, analogous to pulmonary vascular zone conditions, the abdominal venous compartment can be viewed as either a capacitor (zone III abdomen) or as a collapsible Starling resistor (zone II abdomen). This dual nature of the abdominal venous bed can explain how an inspiratory increase in abdominal pressure can increase IVC flow with hypervolaemia, but increase IVC flow with hypovolaemia. Combined generalized increases in abdominal pressure and focal forces over the liver can be shown to be an essential element in the pathogenesis of a Kussmaul's sign. Increases in abdominal pressures produced by active diaphragmatic descent can increase the total IVC venous return by enhancing the splanchnic IVC flow under relatively hypervolaemic conditions, but decrease the total IVC venous return by impeding the non-splanchnic IVC flow under hypovolaemic conditions. Results are presented which suggest that the concept of abdominal vascular zone conditions is useful to understand overall directions of changes in total and regional venous return during normal and obstructed breathing and may provide useful analysis of the haemodynamic events which occur in obstructive sleep apnoea.

Journal Article↗

PubMed1995

Inhaled nitric oxide and extracorporeal membrane oxygenation in persistent pulmonary hypertension of the newborn.

Persistent pulmonary hypertension of the newborn (PPHN) may occasionally require an invasive treatment with extracorporeal membrane oxygenation (ECMO). Inhaled nitric oxide (NO) has recently been introduced as a selective pulmonary vasodilator for treatment of PPHN. We describe a case of PPHN in which neither inhaled NO nor ECMO was effective in reversing pulmonary hypertension. The clinical course of the patient suggested a potential role of NO inhalation in predicting the outcome of ECMO treatment for PPHN.

Administration, Inhalation↗

PubMed1995

A new case of apoA-I deficiency showing codon 8 nonsense mutation of the apoA-I gene without evidence of coronary heart disease.

We report a 39-year-old Japanese man with HDL and apoA-I deficiency as well as data from members of his family. Corneal opacity and a stomatocyte were found but not tonsillar hypertrophy, xanthomas, or splenomegaly. His serum HDL cholesterol, apoA-I, apoA-II, and LDL cholesterol levels were t mg/dL, < 3 mg/dL, 6 mg/dL, and 175 mg/dL, respectively. Plasma triglyceride, phospholipid, apoB, apoC-III, and apoE levels were all within normal limits. Lecithin:cholesterol acyltransferase activity was half of normal, while lipoprotein lipase and hepatic triglyceride lipase activities were within normal limits. ApoA-I deficiency was confirmed by combined isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by an immunoblotting method. We surveyed the apoA-I gene of the patient and five of his family members by direct sequencing after amplification by polymerase chain reaction and found a codon 8 nonsense mutation (TGG --> TAG, Trp --> stop) in exon 3 of the apoA-I gene. The results of a pedigree analysis by DNA sequencing and restricted fragment length polymorphism (Sty I) were consistent with an autosomal codominant trait. Coronary angiography was performed to evaluate coronary atherosclerosis, but no significant luminal narrowing was detected. An intracoronary ultrasound study showed mild intimal hyperplasia in segment 6. In summary, this is a case of apoA-I deficiency without evidence of coronary heart disease.

Adolescent↗

PubMed1995

[Bone lesions in multiple myeloma].

The etiology and pathophysiology of bone lesions in multiple myeloma (MM) and the new treatment for bone lesions in MM are mentioned in this report. The osteoclastic activating factors (OAF) include lymphotoxin (TNF-beta), interleukin 1, tumor necrosis factor (TNF-alpha) and several other cytokines. MM patients with multiple bone lesions have low bone density and low serum 1,25-hydroxyvitamin D level. The measurement of bone mineral density using dual-energy X-ray absorptiometry is useful to evaluate the bone lesions in MM. New diphosphates, which strongly inhibit the activity of osteoclasts, are now expected to be effective in the treatment of bone lesions in MM.

Bone and Bones↗

PubMed1995

Time course of regression of vascular structural changes and its relation to cytosolic free calcium in hypertensives after nilvadipine treatment.

The objective of this study was to assess the regression of vascular structural changes seen in essential hypertension after long-term monotherapy with a calcium antagonist and to clarify the relations to cytosolic free calcium and neurohumoral factors. Blood pressure, minimal vascular resistance (MVR) by strain-gauge plethysmography, cytosolic free calcium in platelets ([Ca2+]i) by Quin 2 method, plasma renin activity (PRA) and plasma aldosterone concentration (PAC), plasma noradrenaline (PNA) and parathyroid hormone (PTH) were measured in 14 essential hypertensives during a placebo period and 2 and 6 months after anti-hypertensive treatment with nilvadipine. Blood pressure decreased from 174 +/- 10/104 +/- 8 mm Hg during the placebo period to 154 +/- 13/93 +/- 14 mm Hg 2 weeks after nilvadipine, and the hypotensive effects were found throughout the 6-month period. Although increased MVR seen in hypertensives did not change after 2 months (from 2.1 +/- 0.7 to 1.9 +/- 0.6 mm Hg/ml/min per 100 ml tissue (PRU), NS), MVR decreased significantly at 6 months (1.6 +/- 0.4, PRU, P < 0.05). Elevated [Ca2+]i seen in hypertensives during the placebo period decreased significantly 2 months after nilvadipine treatment (156 +/- 26 and 140 +/- 27 nM, P < 0.01). The changes in MVR were associated with those in [Ca2+]i 6 months after nilvadipine (r = 0.56, P < 0.05). However, the changes in MVR did not correlate with those in PRA, PAC, PNA or PTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Syk activation by the Src-family tyrosine kinase in the B cell receptor signaling.

Signaling through the B cell antigen receptor (BCR) results in rapid increases in tyrosine phosphorylation on a number of proteins. The BCR associates with two classes of tyrosine kinase: Src-family kinase (Src-protein-tyrosine kinase [PTK]; Lyn, Fyn, Blk, or Lck) and Syk kinase. We have investigated the interaction between the Src-PTK and the Syk kinase in the BCR signaling. In contrast to wild-type B cells, BCR-mediated tyrosine phosphorylation of Syk and activation of its in vitro kinase activity were profoundly reduced in lyn-negative cells. The requirement of the Src-PTK to induce tyrosine phosphorylation and activation of Syk was also demonstrated by cotransfection of syk and src-PTK cDNAs into COS cells. These results suggest that the Src-PTK associated with BCR phosphorylates the tyrosine residue(s) of Syk upon receptor stimulation, enhancing the activity of Syk.

Animals↗

PubMed1994

Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization through distinct pathways.

Stimulation of B lymphocytes through their antigen receptor (BCR) results in rapid increases in tyrosine phosphorylation on a number of proteins and induces both an increase of phosphatidylinositol and mobilization of cytoplasmic free calcium. The BCR associates with two classes of tyrosine kinase: Src-family kinase (Lyn, Fyn, Blk or Lck) and Syk kinase. To dissect the functional roles of these two types of kinase in BCR signaling, lyn-negative and syk-negative B cell lines were established. Syk-deficient B cells abolished the tyrosine phosphorylation of phospholipase C-gamma 2, resulting in the loss of both inositol 1,4,5-trisphosphate (IP3) generation and calcium mobilization upon receptor stimulation. Crosslinking of BCR on Lyn-deficient cells evoked a delayed and slow Ca2+ mobilization, despite the normal kinetics of IP3 turnover. These results demonstrate that Syk mediates IP3 generation, whereas Lyn regulates Ca2+ mobilization through a process independent of IP3 generation.

Animals↗

PubMed1994

The suppressor factor of T suppressor cells induced by tolerogenic conjugates of ovalbumin and monomethoxypolyethylene glycol is serologically and physicochemically related to the alpha beta heterodimer of the T cell receptor.

Ovalbumin-specific, H-2Kd restricted, CD8+ Ts cells of clone 17.2 were shown to produce an OVA-specific Ts cell factor (TsF17.2) possessing the same Ag specificity and MHC restriction as those of the intact Ts cells. The Ts cell clone was generated from a single cell of the spleen of a mouse which had been immunosuppressed by injection of tolerogenic OVA(mPEG)12 conjugate. For the elucidation of the nature of TsF17.2, it was characterized by serologic, physicochemical, and Western blot analyses. It was found that 1) the OVA-specific suppression of in vitro antibody production by TsF17.2 could be blocked by mAb H28-710 which binds to an epitope of the constant region of the alpha-chain of TCR; 2) the TsF17.2 could be sequestered by, and eluted from, immunosorbents prepared by coupling to Affi-Gel Hz the H28-710 mAb or the mAb H57-597 and F23.1 which are specific, respectively, for an epitope of the constant region of the beta-chain and an epitope of the V beta 8 region of the TCR; and 3) the TsF17.2 had a pl of 7.0, m.w. of 84,000, and consisted of two disulfide-linked subunits of 42,000 each. After electroelution from the SDS-PAGE gel, the m.w. 84,000 molecule retained its capacity to suppress in vitro antibody production in an OVA-specific manner. From all these results it was concluded that this Ts cell factor may represent a soluble form of the alpha beta heterodimer of TCR of cloned Ts cells.

Animals↗

PubMed1994

Effects of lead on osteoclast-like cell formation in mouse bone marrow cell cultures.

To examine an effect of lead (Pb) on the process of osteoclast-like cell formation from its progenitors, we used a mouse bone marrow culture system in which osteoclast-like multinucleated cells (MNCs) were formed in response to bone-resorbing agents. In a 9-day culture period, Pb dose-dependently stimulated MNC formation over the concentration range 2-10 microM, whereas at 40 microM Pb, MNC formation declined. In an 11-day culture period, MNC formation reached a maximum at 5 microM Pb and decreased with increasing concentration of Pb at 10-40 microM. Pb-stimulated MNC formation was inhibited by both indomethacin and SC19220, an antagonist of prostaglandin E2 (PGE2) receptor. Pb stimulated the production of PGE2 in marrow cell cultures, suggesting that Pb-stimulated MNC formation is dependent on the production of PGE2. 3-Isobutyl-1-methylxanthine potentiated Pb-stimulated MNC formation and 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, inhibited it. A calcium ionophore A23187 increased Pb-induced MNC formation and verapamil, a calcium channel blocker, depressed it. It is possible that a PGE2-induced increase in the levels of cyclic adenosine 3',5'-monophosphate (cAMP) and calcium ions in marrow cells is involved in Pb-induced MNC formation. Pb and parathyroid hormone showed a synergistic stimulation on MNC formation. From these results, Pb is thought to induce osteoclast-like cell formation by a mechanism involving PGE2 which increases the intracellular levels of cAMP and calcium ions.

1-Methyl-3-isobutylxanthine↗

PubMed1994

Structures of new coumarins and antitumor-promoting activity of coumarins from Angelica edulis.

From the fruits of Angelica edulis Miyabe (Umbelliferae), three new angular furanocoumarins, edulisin III (1), edulisin IV (2), and edulisin V (3), were isolated along with three known coumarins, 2'(S), 3'(R)-3'-isobutyryloxy-4'-acetoxy-2',3'-dihydrooroselol (4), edultin (5), and 2'(S),3'(R)-3'-senecioyloxy-4'-acetoxy-2',3'-dihydrooroselol (6), respectively. The structures of 1 and 2 were established to be 2'(S),3'(R)-3'-(2-methylbutyryloxy)-4'-acetoxy-2',3'-dihydrooro selol and 2'-(S),3'(R)-3'-propyryloxy-4'-acetoxy-2',3'-dihydrooroselol by chemical studies and spectral analyses. Coumarin 3 was proved to be 3'-(2-methylbutyryl-oxy)-4'-angeloyloxy-2',3'-dihydrooroselol++ + by chemical and spectral analyses and H-C COLOC. Coumarins 1-6 were examined for the effects on tumor-promotor induced phenomena in vitro. Among these coumarins, 3 showed the most potent inhibitory activity on 12-O-tetradecanoylphorbol 13-acetate (TPA)-stimulated 32Pi incorporation into phospholipids of cultured cells.

Antineoplastic Agents, Phytogenic↗

PubMed1994

Adoptive transfer of a Th2-like cell line prolongs MHC class II antigen disparate skin allograft survival in the mouse.

The MHC class II alloantigen-reactive CD4+ Th2-like cell line, HR2, was established. It was derived from the spleen cells of C57BL/6 (B6) mice immune to an MHC class II-disparate mutant mouse, B6.CH-2bm12 (bm12) which carries the I-Abm12 antigen. This cell line, HR2, secretes IL-4 and IL-10 in an antigen-specific manner, and can also proliferate in an autocrine manner through IL-4. To investigate the in vivo role of this Th2-like CD4+ T cell line in transplantation immunity, an adoptive cell transfer study using the skin allograft system was performed. Skins grafted from bm12 to B6 were rejected at 12.1 +/- 0.6 days in control B6 mice which received no treatment. Whereas skin graft survival was prolonged in B6 experimental mice which had received 2 x 10(7) HR2 cells, 75% of the grafts survived for > 40 days. Moreover, since skin grafts from fully allogeneic third party donor BALB/c mice were rejected at 12.0 +/- 0.4 days by B6 mice which had received the same number of HR2 cells, it was demonstrated that HR2 is involved in the regulation of bm12 skin graft rejection. Furthermore, cytotoxic T lymphocyte (CTL) activity by spleen cells from HR2 transferred B6 mice was not induced even by in vitro secondary stimulation, although CTL activity was induced well in spleen cells of control B6 mice which had rejected the graft. The underlying mechanism has not been fully clarified; however, these results demonstrate that Th2-like CD4+ T cells suppress allograft rejection.

Animals↗

PubMed1994

Factor-XIIIa-positive cells in normal peripheral nerves and cutaneous neurofibromas of type-1 neurofibromatosis.

Cutaneous neurofibromas consist of heterogenous cell populations including Schwann cells, perineurial cells, and fibroblastlike cells. However, the histogenesis of neurofibromas, particularly the origin and nature of the fibroblastlike cells, is still controversial. Recently, cells containing blood coagulation factor XIIIa have been reported in cutaneous neurofibromas, although their identity is uncertain. In this report, by the combination of double immunohistochemical staining and immunoelectron microscopy, we demonstrate that factor-XIIIa-positive cells are distinct from Schwann cells, perineurial cells, endothelial cells, mast cells, and conventional macrophages, but correspond to the fibroblastlike cells in cutaneous neurofibromas. Such factor-XIIIa-positive cells in cutaneous neurofibromas, however, differ from conventional fibroblasts in the strong expression of HLA-DR antigen and lack of prolyl 4-hydroxylase. Similarly, so-called endoneurial fibroblasts and, occasionally, connective tissue cells within perineurium and epineurium in normal peripheral nerve fibers express factor XIIIa as well as HLA-DR antigen. The results suggest that fibroblastlike cells in cutaneous neurofibromas are probably derived from factor-XIIIa- and HLA-DR antigen-positive connective tissue cells in peripheral nerves. The role of such factor-XIIIa-positive cells in the growth and development of cutaneous neurofibromas is discussed.

Actins↗

PubMed1994

An adult case of histiocytosis X with a vulvar ulcer and multiple bone lesions.

A 62-year-old female with histiocytosis X presented with a vulvar ulcer. Multiple osteolytic lesions were later detected. Histological examination of the ulcerated skin showed diffuse proliferation of histiocytic cells with folded nuclei and pale eosinophilic cytoplasm. Immunohistochemistry revealed S100 protein and vimentin as well as CD1a, CD4, and HLA-DR antigens in the proliferating cells. Electron microscopy demonstrated Birbeck granules in the cytoplasm of the cells. The patient was successfully treated by complete surgical excision of the ulcer followed by radiotherapy for recurrent vulvar erythema.

Female↗

PubMed1994

Proliferating cell nuclear antigen (PCNA) and p53 protein expression in Bowen's disease.

Bowen's disease is a premalignant dermatosis comprised of a clonal proliferation of atypical keratinocytes in the full thickness of the epidermis. To elucidate the relationship between the alteration of the p53 tumor suppressor protein and cell proliferation rate, we immunohistochemically examined the expression of proliferating cell nuclear antigen (PCNA) and p53 protein in 30 cases of Bowen's disease. All the cases exhibited the full-thickness distribution of PCNA-positive cycling cells in the lesional epidermis. Quantitation of PCNA staining by image cytometry revealed a mean labeling index (LI) of 75.1 +/- 20.3. p53 expression was detected in 13 cases (43%). Expression was diffuse (p53 LI > 50) in 9 cases, but focal (p53 LI < 30) in the other four. The mean PCNA LI of p53 diffusely positive cases was significantly greater than that of both p53 focally positive and p53 negative cases (89.3 +/- 10.1 vs 62.7 +/- 21.2, and 70.5 +/- 21.6; p < 0.01, respectively). These findings suggest that a high-level accumulation of p53 protein results in a more increased cell proliferation in Bowen's disease.

Aged↗

PubMed1994

Toward better home respiratory monitoring: a comparison of impedance and inductance pneumography.

Various respiratory monitoring methods have been used as a part of home respiratory care, but none has been accepted as a universal method. Impedance pneumography is the most popular method at present and is used in the form of cardiorespiratory monitoring, but it has limitations for diagnosing obstructive airway problems and a high incidence of false alarms. We evaluated a new investigational method, inductance pneumography, in terms of the incidence of false alarms (waveform out of range), using infants recovering from general anesthesia. They were used for this study because they go through all the stages of sleep in a short period and their relatively long period of light sleep was advantageous in evaluating motion artifact interference. Waveforms went out of range 24.6 +/- 2.9% of the time with impedance pneumography and 15.9 +/- 4.5% with pulse oximeter, but 11.0 +/- 3.4% with inductance pneumography. These differences are statistically significant (P < 0.01). Electrocardiography electrodes for impedance pneumography dislodged briefly in one case but the Respiband dislodged in four cases and the Flex II probe dislodged in three cases, indicating the need for better fixation of sensors. It was found that inductance pneumography, in addition to being able to detect obstructive apnea, has a significantly lower incidence of false alarms. Further elaboration of this method is warranted for better home respiratory monitoring.

Apnea↗

PubMed1994

Functional analysis of Csk in signal transduction through the B-cell antigen receptor.

In B cells, two classes of protein tyrosine kinases (PTKs), the Src family of PTKs (Lyn, Fyn, Lck, and Blk) and non-Src family of PTKs (Syk), are known to be involved in signal transduction induced by the stimulation of the B-cell antigen receptor (BCR). Previous studies using Lyn-negative chicken B-cell clones revealed that Lyn is necessary for transduction of signals through the BCR. The kinase activity of the Src family of PTKs is negatively regulated by phosphorylation at the C-terminal tyrosine residue, and the PTK Csk has been demonstrated to phosphorylate this C-terminal residue of the Src family of PTKs. To investigate the role of Csk in BCR signaling, Csk-negative chicken B-cell clones were generated. In these Csk-negative cells, Lyn became constitutively active and highly phosphorylated at the autophosphorylation site, indicating that Csk is necessary to sustain Lyn in an inactive state. Since the C-terminal tyrosine phosphorylation of Lyn is barely detectable in the unstimulated, wild-type B cells, our data suggest that the activities of Csk and a certain protein tyrosine phosphatase(s) are balanced to maintain Lyn at a hypophosphorylated and inactive state. Moreover, we show that the kinase activity of Syk was also constitutively activated in Csk-negative cells. The degree of activation of both the Lyn and Syk kinases in Csk-negative cells was comparable to that observed in wild-type cells after BCR stimulation. However, BCR stimulation was still necessary in Csk-negative cells to elicit tyrosine phosphorylation of cellular proteins, as well as calcium mobilization and inositol 1,4,5-trisphosphate generation. These results suggest that not only activation of the Lyn and Syk kinases but also additional signals induced by the cross-linking of the BCR are required for full transduction of BCR signaling.

Animals↗

PubMed1994

Effects of erythropoietin treatment on thyroid dysfunction in hemodialysis patients with renal anemia.

The thyroid function was evaluated before and after 6 months of recombinant human erythropoietin (rhEPO) treatment (1,500-9,000 U/week) in 22 hemodialysis patients with hematocrit levels < 25%. Based upon the changes in hematocrit following rhEPO treatment, the patients were divided into two groups: 11 patients with an increase of the hematocrit level > 5% (group I) and 11 patients with an increase < 5% (group II). Before rhEPO administration, the levels of thyroid hormones, especially free thyroxine (T4) and free triiodothyronine (T3), were below the normal range despite normal thyrotropin values in most of the patients (low T4:7 cases in group I and 9 in group II; low T3:10 cases in group I and 10 in group II). RhEPO treatment significantly increased both total amount and free fractions of thyroid hormones in group I, whereas it did not affect these values in group II. Consequently, the pretreatment low T4 or low T3 status was resolved in a substantial number of the patients in group I (low T4:5 cases, low T3:4 cases). In addition, there was a significant correlation between the increases in hematocrit and free T3 in all studied subjects (r = 0.603; p < 0.05). These results suggest that anemia may participate to some extent in the pathogenesis of thyroid dysfunction in hemodialysis patients with renal anemia.

Adult↗