Brain circulatory disturbance in a central venous catheter-inserted child.
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Biomedical subjects
Publications and source records attributed to T Matsuda.
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A case of rapidly destructive arthropathy of the hip in male siblings aged 74 and 76 years is reported. Hip joints of the brothers were destroyed 12 and 4 months after the onset of symptoms, respectively. Results of clinical and laboratory examinations did not show any features of neuropathic, inflammatory, or septic arthropathy. Pathologically in both patients, osteoarthrotic changes with small foci of bone necrosis and nonspecific inflammation and moderate amount of hemosiderosis in the synovium were observed.
Rat strain differences in sensitivity to the promoting effect of sodium L-ascorbate (SA) on the development of urinary bladder tumors were investigated. In experiment 1, WS/Shi (WS), ODS/Shiod/od (ODS), and LEW/Crj (LEW) rats were initiated with 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in their drinking water and subsequently given basal Oriental MF diet (M) with or without a 5% SA supplement. In LEW rats the SA treatment increased the induction of neoplastic lesions in the urinary bladder, whereas WS and ODS animals proved unresponsive to its promoting effects. In experiment 2, WS and F344 rats were maintained on two kinds of commercial basal diets, M and CLEA CA-1 (C), during administration of SA, since dietary factors can influence promoting effects. Feeding M during the promotion period in F344 rats yielded significantly more neoplastic lesions than feeding C, but in WS rats no such dietary influence was apparent. In experiment 3, strain differences in biosynthesis of alpha-2u-globulin (alpha 1a-g) were assessed because both alpha 2a-g in the urine and administration of sodium salts of organic acids such as SA have been reported to be involved in tumor promotion. Immunohistochemical analysis of renal tubules and Western blotting analysis of urine revealed the presence of alpha 2a-g in all three strains examined. These data suggest that differences in susceptibility to promotion are due to genetic factors rather than dietary factors and the ability to synthesize alpha 2a-g.
We describe a patient who presented with hypoxemia and diffuse bilateral pulmonary infiltrates. The diagnosis of eosinophilic pneumonia was confirmed by bronchoalveolar lavage and transbronchial lung biopsy. The remarkable characteristic was reappearance of the symptoms on the patient's return home, suggesting the existence of etiologic agents in his house. An environmental survey of the patient's house yielded Alternaria alternata. A high titer of anti-A. alternata antibody (IgG) was detected in his serum, and the inhalation bronchoprovocation test with A. alternata antigen was positive. This case indicates that A. alternata is a probable cause of eosinophilic pneumonia.
A 2-year-old boy presented with an accessory scrotum associated with penoscrotal transposition and a perineal lipoma. He also had a retrocerebellar arachnoid cyst. The accessory scrotum was resected with concurrent scrotoplasty. The retrocerebellar arachnoid cyst was seen on a subsequent brain computed tomography scan and was left untreated because there was no evidence that the volume was increasing.
We report a case of invasive bladder cancer in which cancer dissemination occurred through a perforation of the vesical wall during transurethral resection of the tumor. A radical cystectomy was performed 1 month later and several clusters of viable cancer cells were histologically identified in a fibrous foreign body granuloma in the paravesicular adipose tissue of the lymphadenectomy specimen. The patient received adjuvant chemotherapy, but developed right inguinal lymph node metastasis 21 months after cystectomy.
The relationship between the conformability of adhesive tape, the mechanical property of the adhesive tape not to interfere with skin movement, and irritation of the skin was investigated. In order to assess the conformability of adhesive tape to the skin, a uniaxial method employing film strips connected to a strain gauge was used to measure the elastic property of the skin, with or without application of various elastic tapes. The tension loaded on the strain gauge was measured while the skin was extended by 15% of its original length in a direction across the humeral axis on the flexor side of the upper right arm. The most elastic adhesive tape showed the best conformity to the skin. The same adhesive tapes were applied on the flexor side of both upper arms so that the tape held a piece of sanitary cotton in place for 24 h. Dermal irritation was not so remarkable in the skin under the inner part of the tapes. On the other hand, the skin reaction was much more severe on the skin under the edge portion of the applied tape which showed poor conformability to the skin. These findings seemed to indicate that the skin reaction was caused by localized distortion of the skin under the edge portion of the applied tapes, during movement of the underlying muscle. Actually, the distortion of the skin surface was great in the areas immediately outside the edge of the applied tape. In conclusion, adhesive tape conformable to skin movement reduced localized distortion of the skin during application, resulting in low irritation at the edge of the applied tape.
Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are closely related G protein-coupled receptors with seven-transmembrane domains. The VIP receptor can bind both VIP and PACAP with high affinity, whereas the PACAP receptor binds only PACAP with high affinity. To elucidate the structural domains involved in a selectivity for VIP binding and the subsequent receptor activation, a series of chimeric receptors between the VIP and PACAP receptors was constructed, expressed in COS-7 cells, and analyzed for ligand binding and cAMP generation. All chimeric constructs bound PACAP with high affinity and subsequently activated cAMP generation similarly to the wild-type receptors. In contrast, profound differences were observed in the potencies of VIP for competition of 125I-labeled PACAP binding to both wild-type receptors and the chimeric receptors. The cAMP responses of these receptors generally correlated with the ability of VIP to compete for PACAP radioligand binding with the exceptions for some particular chimeras. In this report we demonstrate that several domains, including the amino-terminal extracellular domain, the transmembrane domains I and II, and the first extracellular loop of the VIP receptor, are important for the selectivity for VIP binding and responsiveness to VIP. We further show that the third extracellular loop and its proximal domains of the VIP receptor appear to be involved in the VIP recognition, especially the receptor activation process. On the other hand, the direct binding experiments of the VIP radioligand demonstrated that both wild-type receptors and all chimeric receptors have a high affinity binding site for VIP, although this high affinity VIP binding resulted in a biological response only in the VIP receptor or VIP receptor-like chimeras. This suggests that there is a nonbiologically relevant high affinity VIP-binding site within the rat PACAP receptor.
The Janus protein tyrosine kinases (Jaks) play critical roles in transducing growth and differentiation signals emanating from ligand-activated cytokine receptor complexes. The activation of the Jaks is hypothesized to occur as a consequence of auto- or transphosphorylation on tyrosine residues associated with ligand-induced aggregation of the receptor chains and the associated Jaks. In many kinases, regulation of catalytic activity by phosphorylation occurs on residues within the activation loop of the kinase domain. Within the Jak2 kinase domain, there is a region that has considerable sequence homology to the regulatory region of the insulin receptor and contains two tyrosines, Y1007 and Y1008, that are potential regulatory sites. In the studies presented here, we demonstrate that among a variety of sites, Y1007 and Y1008 are sites of trans- or autophosphorylation in vivo and in in vitro kinase reactions. Mutation of Y1007, or both Y1007 and Y1008, to phenylalanine essentially eliminated kinase activity, whereas mutation of Y1008 to phenylalanine had no detectable effect on kinase activity. The mutants were also examined for the ability to reconstitute erythropoietin signaling in gamma2 cells, which lack Jak2. Consistent with the kinase activity, mutation of Y1007 to phenylalanine eliminated the ability to restore signaling. Moreover, phosphorylation of a kinase-inactive mutant (K882E) was not detected, indicating that Jak2 activation during receptor aggregation is dependent on Jak2 and not another receptor-associated kinase. The results demonstrate the critical role of phosphorylation of Y1007 in Jak2 regulation and function.
A rare case of Hodgkin's disease which initially presented with a thyroid tumor in an 18-year-old-man is reported. The tumor involved most of the thyroid gland but was well demarcated, and the border between the tumor and the remnants of the thyroid gland was relatively clear, suggesting secondary Hodgkin's disease involving the thyroid gland. Histologic examination of the tumor revealed nodular sclerosing Hodgkin's disease composed of many peculiar osteoclast--like giant cells and a few typical Reed--Sternberg cells in the background of dominant eosinophils. With an immunophenotypic study it was shown that these giant cells were positive for the monoclonal antibodies LeuM1 and BerH2, but negative for LCA. Thus the histological diagnosis was clearly confirmed.
BACKGROUND: Over the last few years, evidence has accumulated that cyclic nucleotide phosphodiesterase (PDE) 3 and/or PDE4 inhibitors may be useful for the treatment of asthma. The present study was designed to examine the effect of a selective orally active PDE3 inhibitor, cilostazol, on bronchial hyperresponsiveness (BHR) of asthma. METHODS: The effect of a single oral dose of cilostazol on BHR was studied in 10 elderly patients with clinically stable asthma, with a mean age of 59.5+/-4.8 years, in a double-blind, crossover, placebo-controlled study. Each subject received 100 mg of cilostazol, 200 mg of theophylline as a positive control or a placebo in a random order. The subjects underwent a methacholine challenge test 3 h after each drug administration on three occasions separated by 2 weeks. RESULTS: The geometric mean value of the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC20-FEV1) with cilostazol was 0.48 mg/ml [geometric standard error of the mean (GSEM), 1.40] which was significantly (p<0.01) greater than that with the placebo [0.25 mg/ml (GSEM, 1.36)]. The value with theophylline [0.32 mg/ml (GSEM, 1.54)] did not differ significantly from that with cilostazol or the placebo. Baseline forced vital capacity (FVC) and FEV1 values significantly (p<0.05 and p<0.001, respectively) increased with cilostazol from 2.73+/-0.25 and 1.52+/-0.17 to 2.86+/-0.23 and 1.65+/-0.17 liters, respectively. Theophylline did not significantly increase the FVC or FEV1 value. CONCLUSION: It is suggested that the PDE3 inhibitor, cilostazol, has bronchodilator and bronchoprotective effects in elderly asthmatics.
The cause of airway resistance that develops during an asthma attack is not fully understood. Besides bronchospasm and airway edema, a surfactant dysfunction has been suggested as a reason for an increase in airway resistance. This study sought to determine if surface activity of airway fluid is altered in acute asthmatic attacks. Sputa were collected serially from seven patients with acute asthmatic attacks and compared with that of normal subjects (n = 15) and subjects with stable asthma (n = 14). Sputa were analyzed for minimal surface tension (STmin), phospholipids (PL), and total proteins (TP). There were no significant differences in STmin, PL, and TP between sputa from normal subjects and subjects with stable asthma. In the acute phase of the attack, TP, TP/PL ratio, and STmin significantly increased. However, in the recovery phase of the attack, TP/PL ratio and STmin significantly decreased. These data demonstrated that surface properties of airway fluid deteriorated in the early phase of the asthma attack, but were ameliorated in the recovery phase possibly by the surfactant recruitment. The drastic changes in surface activity of sputum suggest that changes in airway surfactant may be partly involved in the pathogenesis of the airway obstruction during asthmatic attack.
In pulmonary tuberculosis, the proportion of lymphocytes, particularly that of CD4+ T lymphocytes, was increased in bronchoalveolar lavage fluid (BALF), reflecting their protective role against mycobacterial infections. In order to elucidate the mechanisms of lymphocyte accumulation in lungs, we measured the levels of chemokines with potent lymphocyte chemotactic activities, including interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and, regulated on activation, normal T-cell expressed and secreted (RANTES) present in BALF from patients with pulmonary tuberculosis in acute (n = 10) and convalescent phases (n = 6), as well as normal subjects (n = 10). During the acute phase of the disease, the proportions of lymphocytes and neutrophils were increased, as reported in previous studies. The levels of IL-8, MCP-1, and RANTES in the acute phase of pulmonary tuberculosis were also markedly elevated as compared with those of normal subjects. MCP-1 and RANTES, but not IL-8 levels present in BALF, decreased in the convalescent phase. Moreover, the concentration of RANTES correlated significantly with the absolute number of CD4+ cells in BALF. These data suggest that chemotactic cytokines are differentially produced and participate in the host response to Mycobacterium tuberculosis infection.
We investigated the characteristics of GABAergic neurons in the rat suprachiasmatic nucleus (SCN) in normal untreated rats by examination of co-expressed peptides. We adopted double labeling in situ hybridization using a digoxigenin-labeled glutamic acid decarboxylase (GAD) riboprobe and 35S-labeled peptide riboprobes. GAD mRNA-positive neurons were distributed throughout the SCN from the rostal to the caudal pole. In the dorsomedial part of the SCN, most GAD mRNA-positive neurons co-expressed arginine vasopressin mRNA. In the ventrolateral part of the SCN, about two thirds of GAD mRNA-positive neurons co-expressed vasoactive intestinal peptide (VIP) mRNA. Co-expression of GAD and somatostatin mRNA was observed in virtually all neurons of the intermediate part of the SCN. In contrast, these peptidergic traits were poorly expressed in hypothalamic GABAergic neurons outside the SCN. Vasopressin mRNA-positive cells in the supraoptic nucleus did not express GAD mRNA, and co-expression of somatostatin mRNA and GAD mRNA was rare in the periventricular hypothalamic nucleus. Similarly, the VIP mRNA co-expression ratio of GABAergic neurons in the cerebral cortex was far lower than that in the SCN.
Ultrasonically nebulized distilled water-induced bronchoconstriction (UNDW-IB) is specific to asthma. The mechanisms underlying UNDW-IB are not fully understood, and no reproducible animal model has been reported. The purpose of this study was to develop a guinea-pig model of UNDW-IB. Ultrasonically nebulized distilled water (UNDW) was inhaled 20 min after an aerosolized antigen challenge in passively sensitized and artificially ventilated guinea-pigs. UNDW was also inhaled 5 and 20 min after 0.1 mg x mL(-1) methacholine inhalation in nonsensitized animals. In addition, 0.1 mg x kg(-1) S-1452, a thromboxane A2 antagonist, or saline was given intravenously 5 min before UNDW inhalation in sensitized animals. The inhalation of UNDW caused bronchoconstriction, when inhaled 20 min after an antigen challenge in sensitized guinea-pigs. UNDW inhalation did not produce bronchoconstriction after saline inhalation in nonsensitized or sensitized guinea-pigs, or after antigen inhalation in nonsensitized animals. Methacholine-induced bronchoconstriction did not evoke UNDW-IB. Neither did S-1452 reduce the UNDW-IB. In conclusion, the guinea-pig model of ultrasonically nebulized distilled water-induced bronchoconstriction developed in this study suggests that allergic reaction, but not bronchoconstriction, can induce bronchial hyperresponsiveness to ultrasonically nebulized distilled water, and that thromboxane A2 is not involved in ultrasonically nebulized distilled water-induced bronchoconstriction.
PURPOSE: To determine the effects of irinotecan (CPT-11) given in combination with etoposide (VP-16) in metastatic non-small-cell lung cancer (NSCLC), to evaluate response and survival rates, and to determine the qualitative and quantitative toxicities of the combination chemotherapy. PATIENTS AND METHODS: Sixty-one metastatic NSCLC patients received concurrent administration of CPT-11 and VP-16 for 3 days with recombinant human granulocyte colony-stimulating factor (rhG-CSF) support. RESULTS: Fifty-nine patients were assessable for response and all 61 patients were assessable for toxicity and survival. Fifty-six patients were treated with two or more courses of chemotherapy. Thirteen patients achieved a partial response (PR), 36 showed no change (NC), and 10 showed progressive disease (PD). The overall response rate was 21.3% (95% confidence interval, 12.9% to 33.1%). The median duration of PRs was 141 days (range, 62 to 299). Of the hematologic toxicities, 14 (23%) and 24 (39%) patients experienced grade 3 or 4 leukopenia and neutropenia, respectively. The toxicities were feasible. Treatment-related death occurred in one patient who suffered hypovolemic shock induced by hematemesis. The median survival time was 10.0 months and the 1-year survival rate was 36.1%. CONCLUSION: Combination chemotherapy with concurrent administration of CPT-11 and VP-16 with rhG-CSF support was only modestly effective against metastatic NSCLC, with feasible toxicities of moderate diarrhea and pulmonary toxicity. The results were equivalent to those expected with either cisplatin-based chemotherapy or with CPT-11 alone.
A 65-year-old man was admitted with a diagnosis of arteriosclerosis obliterans. He had a 3-month history of intermittent claudication of the right leg. Physical examination revealed absence of pulsation of the right posterior tibial artery. Contrast angiography of lower extremities showed several obstructive lesions below the right popliteal artery. As interventional and surgical approached were not indicated, the patient was treated with exercise with heparin pretreatment (5,000 IU). As a result, walk distance on a floor was increased from 400 m to 2,000 m, and repeat magnetic resonance angiography revealed increased flow to the right lower extremity. Thus, he was successfully treated with exercise and heparin pretreatment without any side effects.
The mechanism of induction of reactive astrocytes (activation of astrocytes) that is observed in brain pathological conditions is not fully elucidated, and there is little information on the cell death of astrocytes. This mini-review summarizes our studies on the activation and cell death of astrocytes. Microinjection of endothelin-3 or the endothelinB-receptor agonist ala1,3,11,15-endothelin-1 enhanced the injury-induced increase in glial fibrillary acidic protein staining in rat neostriatum. Under these conditions, the receptor agonist did not affect the number of microglia/macrophage. The findings suggest that the signal cascade via endothelinB receptors in astrocytes is involved in induction of reactive astrocytes. We also found that Ca2+ depletion followed by reperfusion with Ca(2+)-containing medium caused cell death in cultured astrocytes (Ca2+ paradox-like injury). The study, carried out by the use of a specific antisense oligomer, provides direct evidence that Ca2+ paradox-like injury is mediated by the Na(+)-Ca2+ exchanger in the reverse mode. The injury was prevented by inhibitors of the Na(+)-Ca2+ exchanger and heat shock protein. Heat shock protein may affect processes downstream of the increase in intracellular Ca2+ concentration. Further studies on activation and cell injury of astrocytes will contribute to the development of new drugs that modulate the function of astrocytes.