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Biomedical subjects

M Takeda

Publications and source records attributed to M Takeda.

At least 397 records · Page 22Linked to original sources

Three-dimensional ultrastructure of the perivascular space in the rat thymus.

The overall architecture and structure of the perivascular space in the rat thymus were studied by light microscopy using silver-impregnated sections and sections stained immunohistochemically with anti-cytokeratin antibody, and by transmission and scanning electron microscopy (TEM and SEM). In silver-impregnated sections, the perivascular space was delimited by a thin sheath of delicate argyrophilic fibers from the thymic parenchyma in the cortico-medullary region and medulla. This space was continuous with the septal connective tissue, indicating that this was the connective tissue compartment rather than with the epithelial compartment of the parenchyma. In the medulla, the perivascular space widened at places, where the argyrophilic sheath was often discontinuous and the boundary between the perivascular space and parenchyma was indistinct. Lymphatics were located in the perivascular space of the corticomedullary region and sometimes in the wide perivascular space of the medulla. The presence of a thymic epithelial sheath surrounding the perivascular space was confirmed by light microscopy of anti-cytokeratin antibody immunostained sections and by TEM. SEM observations revealed three-dimensionally that the epithelial sheath lined by collagen fibrillar (i.e., argyrophilic) layer form a rather continuous tubular structure in the cortico-medullary region, while it often interrupted in the medulla. These findings indicated that the perivascular space (i.e., the connective tissue compartment) is extensively open to the parenchyma (i.e., the epithelial compartment) in some portions of the medulla, where medullary lymphocytes are probably freely exposed to blood borne substances similar to the peripheral lymphoid tissues.

Animals↗

Retroperitoneal laparoscopic adrenalectomy for functioning adrenal tumors: comparison with conventional transperitoneal laparoscopic adrenalectomy.

PURPOSE: We attempted to confirm the possibility and feasibility of laparoscopic adrenalectomy via the retroperitoneal approach, and to compare results of the transperitoneal and retroperitoneal approaches. MATERIALS AND METHODS: Three men and 8 women (mean age 39.6 years) with functioning adrenocortical tumors (primary aldosteronism in 5 and Cushing's syndrome in 6) underwent laparoscopic adrenalectomy via the retroperitoneal approach using a balloon dissection technique and a newly developed ultrasonic aspirator. Results were compared to those of 27 cases of transperitoneal laparoscopic adrenalectomy. RESULTS: Although the retroperitoneal approach was successful in all 5 patients with primary aldosteronism, it succeeded in only 2 of the 6 cases of Cushing's syndrome. In 3 Cushing's syndrome cases the retroperitoneal approach was changed to the transperitoneal laparoscopic approach due to difficulty in exploration. Open laparotomy was required in 1 case of left Cushing's syndrome because of an inadvertent pancreatic injury. Subcutaneous emphysema developed in 6 patients without hypercapnia or prolonged postoperative symptoms. Mean operative time and blood loss, and time to oral intake and ambulation were 248.3 minutes, 151.4 ml., and 1.55 and 2 days, respectively. There was no difference between retroperitoneal and conventional transperitoneal laparoscopic adrenalectomy in regard to these factors or to convalescence. CONCLUSIONS: Retroperitoneal laparoscopic adrenalectomy is feasible for primary aldosteronism. However, Cushing's syndrome is presently a much more difficult indication than primary aldosteronism for this new operative technique.

Adrenal Cortex Neoplasms↗

[Study of choroidal vascular lesions in central serous chorioretinopathy using indocyanine green angiography].

We performed fluorescein and indocyanine green (ICG) angiographies in 56 patients with central serous chorioretinopathy, and studied the choroidal lesions. In the early phase, choroidal filling with ICG was delayed in 77% in the area including focal leakage. Hypofluorescent findings around the site of focal leakage persisted through the phase in 23%, and we think this finding was caused by filling defect of the choriocapillaris. In the late phase, choroidal tissue staining by ICG was present in 82% in the area including focal leakage. Multiple areas of choroidal staining were also present in unaffected areas in 43% and in 62% of fellow eyes. Choroidal tissue staining by ICG was revealed in 48% in the area of choroidal filling delay, and this finding persisted after focal leakage had disappeared following photocoagulation. We think this finding was caused by choroidal vascular hyperpermeability. These findings suggest that choroidal circulatory disturbance and choroidal vascular hyperpermeability play a causative role in damage to the retinal pigment epithelium in central serous chorioretinopathy.

Adult↗

[Accumulation of 14C-cystine in inherited cataractous rat lens].

This study was designed to investigate the formation of mixed disulfides of protein and glutathione (GSH) in the cataractous lens. We compared the changes in accumulation of 14C-cystine in cultured inherited cataractous rat lens (ICR/f) during cataractogensis with those in Wistar strain rats. The accumulation of 14C-cystine in water insoluble protein (WIP) of the lens was increased, especially in lens recognized cataract. The radioactivity accumulated in the WIP was released by incubation with 2-mercaptoethanol (2-ME), dithiothereitol (DTT) and GSH. The accumulation of 14C-cystine in WIP was inhibited by pretreatment with DTT. The existence of some materials in the lens-which combined with S-S compounds became clear. A large part of the materials is present in WIP which is increased along with the lens opacification. We surmised that the accumulation of 14C-cystine was related to the reaction of protein-glutathione disulfide (PSSG).

Aging↗

Classification system of complications in neuroleptic malignant syndrome.

Our group treated 13 cases of neuroleptic malignant syndrome (NMS) over a period of 8 years. Based on the clinical severity of complications, the cases were classified into three types: mild, with no complications; moderate, with only respiratory disturbance; and severe, with respiratory disturbance and renal failure. The major complications affecting the prognosis of NMS are respiratory disturbance and renal failure. Renal failure is also associated with the occurrence of disseminated intravascular coagulation and rhabdomyolysis. The proposed classification system for NMS patients is useful in selecting the appropriate therapeutic strategy for this disorder. The clinical data were analyzed to determine the factors in the process of deterioration in NMS.

Adolescent↗

[Preventive concomitant aortic root replacement for annuloaortic ectasia in a patient with Marfan syndrome undergoing mitral valve replacement for mitral regurgitation].

A 28-year-old woman presented with Marfan syndrome combined with severe mitral regurgitation and annuloaortic ectasia. The ascending aorta was dilated to 48 mm in diameter without aortic regurgitation. Considering the increased operative risk due to complication with aortic dissection, simultaneous replacement of the mitral valve and aortic root were performed. Her postoperative course was uneventful. Several options of the surgical treatment for Marfan syndrome are discussed.

Adult↗

[A case of juvenile Huntington's disease presenting dystonia and confirmed by DNA analysis].

We reported a 13-year-old boy with juvenile Huntington disease diagnosed by DNA analysis. Symptoms started with dysarthria at 6 years of age, which was followed by progressive dysgraphia and gait disturbance due to dystonia from 7 years, and by epileptic seizures from 12 years. Magnetic resonance imaging revealed atrophy of the bilateral caudate nuclei and T2- and proton-weighted high intensity area in both putamina. The CAG (cytosine-adenine-guanine) trinucleotide repeat on chromosome 4 p16 was markedly expanded to 81. For a child with dystonia with mental deterioration, juvenile Huntington disease should be considered in the differential diagnosis.

Adolescent↗

Arachidonic acid inhibits myelin basic protein phosphorylation in cultured oligodendrocytes.

Protein phosphorylation is a well-known mechanism by which extracellular molecules or factors transduce their signals into intracellular effects. In the context of myelin assembly, phosphorylation of major myelin proteins affects the electrostatic repulsion between adjacent proteins within myelin structure and therefore constitutes one of the mechanisms by which myelin stability is regulated. We report here that arachidonic acid (AA) decreases the phosphorylation of myelin basic protein (MBP) both in the absence and in the presence of phorbol esters in cultured rat oligodendrocytes (OLGs). The effect of AA on MBP phosphorylation is not mediated by cyclooxygenase products, though the possibility that leukotrienes or other epoxides may have a role cannot be excluded. AA did not act by inactivation of protein kinase C. Based on our findings from gadolinium and low K+ experiments, we conclude that inhibition of MBP phosphorylation is not dependent on AA-induced increases in OLG Ca(i), but rather on its depolarizing action. We have thus demonstrated that a brief exposure to AA, which either acts as a diffusible paracrine signal to OLGs or as a signal transducer, can trigger changes in protein phosphorylation in OLGs/myelin via ionic signaling events at the plasma membrane.

Animals↗

Effects of tachykinins on rapidly adapting pulmonary stretch receptors and total lung resistance in anesthetized, artificially ventilated rabbits.

In anesthetized, artificially ventilated rabbits not treated with thiorphan (2 mg/kg), a neutral endopeptidase (NEP) inhibitor, substance P (SP) and neurokinin A (NKA) in doses from 0.2 to 2.7 microg/kg produced dose-related increases in rapidly adapting pulmonary stretch receptor (RAR) activity without any significant changes in total lung resistance (RL), whereas neurokinin B (NKB) at the same concentrations did not significantly alter either RAR activity or RL. In comparison with the excitatory responses of RAR activity to SP and NKA, the magnitudes of increased receptor activity evoked SP were significantly larger than those after NKA administration. The rank order of tachykinins for RAR stimulus potency was SP > NKA > KB. Pretreatment with thiorphan potentiated the increases of RAR activity and RL induced by SP but had no effect on the RAR and RL responses to NKA and NKB. Subsequent administration of L 659, 877 (a selective NK2 receptor antagonist, 2. 3 and 7.6 microg/kg) that dose-dependently inhibited NKA-induced RAR stimulation did not significantly influence augmentation of the RAR and RL responses to SP. Administration of atropine (2 mg/kg, n = 6) in thiorphan-treated rabbits, which had no effect on NKA- and NKB-induced RAR stimuli, significantly attenuated the increases of RAR activity and RL induced by SP. These results suggest that tachykinin-induced RAR stimulation is mediated by the activation of NK2 receptors, probably involving participation of NK1 receptors. Furthermore, potentiation of the increases of RAR activity and RL produced by SP administration in the presence of thiorphan is partly mediated by facilitation of cholinergic neurotransmission.

Animals↗

Vaginal stone in a male patient with true hermaphroditism.

A 31-year-old male with true hermaphroditism and a 46, XX karyotype who underwent gonadectomy and extirpation of the internal sex organs at the age of 4 had a large stone 4 cm in diameter in the residual male vagina. He complained of pain on micturition, hematuria, and rectal pressure. Urethroscopy and retrograde urethrography disclosed an ostium of the male vagina in the prostatic urethra, and an impacted intravaginal stone. Transurethral electrohydraulic lithotripsy was performed. Extracorporeal shock wave lithotripsy and transurethral lithotripsy were performed for the residual stones. All stones and fragments were spontaneously passed. The stone was composed of calcium phosphate and ammonium acid urate.

Adult↗

Supporting cells as phagocytes in the olfactory epithelium after bulbectomy.

Macrophages are known to be phagocytes in the olfactory epithelium of adult rats. The participation of other cell types in phagocytosis in association with the cell death process was examined in the olfactory epithelium after unilateral bulbectomy of neonatal mice. The terminal deoxynucleotidyl transferase (TdT)-mediated biotinylated dUTP nick end-labeling (TUNEL) method revealed that the process of olfactory cell death consists of acute and chronic periods. The number of apoptotic cell profiles on the operated side peaked at 1 day, and the percentage of labeled cell profiles was 13.6%. The number of dying cells rapidly decreased at 3 days and decreased further at 5 days. Only 3% of the cells were labeled at 5 days. The percentage of dying cells increased again at the end of first postoperative week and remained two- to four-fold higher than control values for 2 months (4.7-5.3%). Electron micrographs of sections from early postbulbectomy stages (1-7 days) showed that as many as 30% of supporting cell profiles contained apoptotic bodies, cellular debris and phagosomes in the cytoplasm. The number of supporting cell profiles containing phagosomes declined to a plateau 2 weeks following bulbectomy and remained at 8-12% of the supporting cell population for 2 months. The results indicate that supporting cells in the olfactory epithelium play a significant role in phagocytosis in both acute and chronic of cell death after bulbectomy in newborn mice. However, supporting cells are not the exclusive phagocytic cell type in the bulbectomized epithelium; a small number of macrophages was also observed. Moreover, the phagocytosis by supporting cells was observed in unperturbed epithelium in the early stages during postnatal development.

Animals↗

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level.

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperiodol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35 degrees C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.

Animals↗

Improvement of metabolic disorders and visceral fat obesity by the beta 3-adrenoceptor agonist (R*,R*)-(+/-)-methyl-4-[2-[2-hydroxy-2 -(3-chlorophenyl)ethylamino]propyl]-phenoxyacetate hydrobromide (BRL35135A) in genetically obese rodents.

The effects of BRL35135A ((R*,R*)-(+/-)-methyl-4-[2-[2-hydroxy-2 -(3-chlorophenyl)ethylamino]propyl]-phenoxyacetate hydrobromide), a beta 3-adrenoceptor agonist, on visceral and subcutaneous fat weight and metabolic disorders were studied in genetically obese C57BL/KsJ db/db mice and Zucker fa/fa rats. In db/db mice, four weeks of oral administration of BRL35135A (0.5 and 5 mg/kg/day) decreased body weight gain and reduced white fat weight. The rates of reduction of white fat weight were in the order mesenteric fat > retroperitoneal fat > subcutaneous fat. In fa/fa rats, daily administration of BRL35135A (0.05 mg/kg/day)) for 6 weeks reduced the visceral white fat weight/total energy intake ratio, particularly for mesenteric fat, without any clear effect on body weight gain. This tendency of the compound to exert effects on visceral fat was consistent with the findings that the effect of BRL37344 ((R*,R*)-(+/-) -methyl-4-[2-[2-hydroxy-2-(3-chlorophenyl)ethylamino]propyl]-phenoxyacet ic acid), an active metabolite of BRL35135A, on the lipolytic activity of isolated adipocytes and the tissue concentration of [14C]BRL37344 in male Wistar rats were each greater in visceral fat than in subcutaneous fat. Moreover, BRL35135A at 0.05 mg/kg/day elevated serum insulin levels and improved hyperglycemia in db/db mice without reducing body weight gain, whereas at doses of 0.5 and 5 mg/kg/day it ameliorated hyperglycemia and hyperlipidemia, and tended to decrease serum insulin levels. In fa/fa rats, BRL35135A (0.005 mg/kg/day) was also effective in improving hyperinsulinemia, glucose intolerance, and hypertriglyceridemia without any effect on body weight gain or fat distribution. These findings suggest that the improvement of metabolic disorders by BRL35135A may be due to improvement in insulin resistance as well as reduction of visceral fat weight.

Adipose Tissue↗

Abrogation of apoptosis induced by DNA-damaging agents in human bladder-cancer cell lines with p21/WAF1/CIP1 and/or p53 gene alterations.

The p53-inducible cyclin-dependent kinase inhibitor, p21/WAF1/CIP1 (p21), plays a pivotal role in the G1 arrest or apoptosis of cells exposed to genotoxic stimuli. To determine whether p21 is a putative tumor-suppressor gene, p21 status was investigated in 4 human bladder-cancer cell lines of known p53 status. A p21-gene mutation, one base-pair insertion at codon 20 resulting in a chain-termination change at codon 35, was observed in one cell line, HT1376, suggesting structural or functional alteration of the p21 protein. When exposed to DNA-damaging agents, cisplatin or mitomycin C, apoptosis was induced in RT4 with the wild-type (wt) p53/wt p21, whereas T24 with the p53 non-sense mutation/wt p21 was resistant. Of the other 2 cell lines with the p53 mis-sense mutation, apoptosis was induced in SCaBER with the wt p21, but HT1376 with the p21 frame-shift mutation was fairly resistant. These findings suggest that not only p53 alteration, but also p21 alteration, is important to prevent apoptosis induced by DNA-damaging agents. When exposed to these agents, p53 and p21 expression was increased in RT4, and not induced in T24. p53 was not induced, but p21 expression was increased in SCaBER, whereas p53 expression was increased but p21 expression was absent in HT1376. Thus, p21 expression itself may have an important role in the induction of apoptosis by DNA-damaging agents.

Apoptosis↗

Tetrapeptide DEVD-aldehyde or YVAD-chloromethylketone inhibits Fas/Apo-1(CD95)-mediated apoptosis in renal-cell-cancer cells.

The apoptotic machinery has been intensively investigated, and interleukin-1-beta-converting enzyme (ICE) and its homologs directly mediate apoptosis by means of their unique protease activity. Fas/Apo1 (CD95), a member of the TNF-receptor family, mediates apoptosis by binding to its ligand, which is mainly expressed on lymphocytes. Here, we investigated the expression and function of both molecules in renal-cell cancer (RCC). The expression of Fas was examined in 6 RCC cell lines by immunoblotting and all of them expressed Fas. ICE and CPP32/YAMA were also identified among the cell lines. We earlier examined ACHN cells expressing low levels of BCL-2, as well as KRC/Y cells with high levels of BCL-2. Here, we found that the anti-Fas monoclonal antibody, CH-11, induced apoptosis in a dose-dependent fashion more remarkably in ACHN cells. Pre-incubation with the tetrapeptide YVAD-chloromethyl-ketone or DEVD-aldehyde inhibited Fas-mediated apoptosis. These findings suggest that, in RCC, apoptosis is induced by lymphocytes bearing Fas-L, and that it is achieved through the proteolytic action of CPP32/YAMA and/or ICE, or another member of the ICE/ced-3 protease family.

Amino Acid Chloromethyl Ketones↗