Recurrent respiratory failure in a patient with 3243 mutation in mitochondrial DNA.
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Biomedical subjects
Publications and source records attributed to N Nagata.
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We have investigated the effects of actinomycin D on mouse ear oedema induced by capsaicin, neuropeptides, and established inflammatory mediators. Actinomycin D (0.5 mg/kg, i.v.) significantly (P < 0.01) inhibited ear oedema induced by topical application of capsaicin, while adriamycin (6.0 mg/kg, i.v.) and cycloheximide (6.0 mg/kg, i.v.) had no effect on oedema. The ear oedema induced by intradermal injection of neuropeptides such as mammalian tachykinins, calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP), was markedly (P < 0.05, P < 0.01 or P < 0.001) suppressed by actinomycin D. The drug was also effective (P < 0.01 or P < 0.001) in inhibiting bradykinin (BK)- and compound 48/80-induced ear oedema, but did not inhibit oedema induced by histamine, 5-HT, leukotriene C4 (LTC4), and platelet activating factor (PAF) at a dose of 1 mg/kg. In mast cell-deficient W/WV mice, actinomycin D (1.0 mg/kg, i.v.) failed to inhibit substance P (SP)-induced ear oedema whereas spantide (0.5 mg/kg, i.v.) was an effective (P < 0.01) inhibitor of oedema formation. Furthermore, actinomycin D (10-100 microM) dose-dependently prevented histamine release from rat peritoneal mast cells evoked by SP, compound 48/80, and the ionophore A23182, respectively. These results strongly suggest that an inhibitory effect of actinomycin D on neurogenic inflammation is due primarily to the prevention of mast cell activation mediated by neuropeptides, rather than an interaction with DNA or receptors of neuropeptides.
We examined the involvement of substance P (SP) in mouse ear oedema induced by topical application of capsaicin (250 micrograms/ear). Reapplication of capsaicin at 4 h, 24 h, and 48 h after initial treatment did not induce a second oedema response. Oedema induced after the second application was significantly (p < 0.01 or p < 0.001) suppressed for up to 30 days but was observed when capsaicin was applied 40 days after initial treatment. Topical pretreatment of ears with capsaicin at 4 h, 24 h and 48 h before i.v. injection of SP (5 micrograms/kg) did not cause a significant inhibition of plasma extravasation in ear skin. NK1 receptor antagonists such as RP 67580 (ED50:0.19 mg/kg, i.v.), spantide II (ED50:0.33 mg/kg, i.v.), and GR 82334 (ED50:0.26 mg/kg, i.v.), inhibited capsaicin-induced ear oedema, whereas SR 48968 (2.0 mg/kg, i.v.), a NK2 receptor antagonist, had no effect. Furthermore, RP 67580 (0.5 kg/mg, i.v.) inhibited the oedema response induced by reapplication of capsaicin at 50 days after initial treatment. These results indicate that tachyphylaxis of capsaicin-induced oedema is reversible and suggest that this response may be due mainly to a reduction of SP in sensory neurones but not to any loss of responsiveness of NK1 receptors. We also conclude that SP and NK1 receptors are involved predominantly in the development of capsaicin-induced mouse ear oedema.
Progressive common atrioventricular valve regurgitation is a serious condition in children with a univentricular heart. We developed a repair procedure that consists of using a Teflon tape bridge and total circular annuloplasty to divide the common atrioventricular valve into two atrioventricular valves. This procedure was performed in 2 infants, and the results were satisfactory. Details of the technique are described.
To compare patterns of expression between the Ngrol genes of N. glauca and the Rirol genes of Agrobacterium rhizogenes, we performed fluorometric and histochemical analysis of transgenic genetic tumors on the hybrid of Nicotiana glauca x N. langsdorffii (F1) that harbored a beta-glucuronidase (GUS) reporter gene fused to the promoter of NgrolB, NgrolC, RirolB or RirolC. The promoters of NgrolB and NgrolC had 2- to 3-fold lower activity than those of RirolB and RirolC. However, the changes in patterns of GUS activity caused by deletion of NgrolB and NgrolC promoters were similar to those of RirolB and RirolC promoters. This result suggests that the cis-acting sequences that regulate the level of expression of RirolB and RirolC are conserved in the NgrolB and NgrolC promoters. Furthermore, an auxin dependent (NAA-dependent) increase in GUS activity was observed in the case of NgroB-GUS and RirolB-GUS. Histochemical analysis showed GUS activity encoded by both NgrolB-GUS and RirolB-GUS in normal-type F1 transgenic plants was located in meristematic zones, while that encoded by NgrolC-GUS and RirolC-GUS was detected mainly in vascular systems of various organs. Thus, the patterns of expression of the Ngrol genes were the same as those of the Rirol genes in terms of promotion by auxin and tissue-specificity, indicating that regulatory mechanisms for both sets of genes have been conserved during the evolution of the genus Nicotiana after transfer from a progenitor of Agrobacterium to that of Nicotiana.
We tried to detect human cytomegalovirus (HCMV) DNA in CD4+ and CD8+ T lymphocytes from fourteen infants with HCMV hepatitis using polymerase chain reaction (PCR) assay. HCMV was isolated from their urine and anti-HCMV IgM antibody was detected in their sera. One set of primers were designed from a region--a major immediate early (IE) gene. We detected HCMV IE DNA in the specimens obtained from six infants. HCMV IE DNA was detected from CD4+ cells in two cases and from CD8+ cells in one. In three cases, HCMV IE DNA was detected from both CD4+ and CD8+ cells. We also studied the relationship between HCMV infection and serum levels of cytokines. We determined serum levels of interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-alpha) and soluble interleukin 2 receptor (sIL-2R) which were associated with the activation of T lymphocytes by enzyme immunoassay. In the acute phase of HCMV infection, titers of sIL-2R were correlated with serum levels of liver enzymes in some cases. IL-4 and TNF-alpha activities were not detected in sera. It is likely that expression of viral genome on T lymphocytes as well as activities of some cytokines are associated with active HCMV infection.
More than forty chalcone derivatives were synthesized to examine their structure-activity relationship against tumorigenesis. As a primary screening test, the inhibitory activities of the chalcones for the 32Pi-incorporation into phospholipids of HeLa cells enhanced by 12-O-tetradecanoyl-phorbol 13-acetate (TPA) were examined. 3-Hydroxy-chalcone derivatives possessing methyl group in 3'-, 4'-, or 2'-position and isoliquiritigenin homologs showed potent inhibitory activities in the phosphorylation test, which suggests their antitumorigenic effects.
We investigated the involvement of serotonin (5-HT) in mouse ear edema induced by topical application of capsaicin (250 micrograms/ear). Application of capsaicin to the ear caused degranulation of mast cells in skin connective tissue. Capsaicin-induced ear edema was significantly inhibited by preadministration of 5-HT2 receptor antagonists such as ketanserin (2 mg/kg, i.v.) and LY 53857 (1 mg/kg, i.v.), but not 5-HT1-, 5-HT3- and 5-HT4-receptor antagonists. Intradermal injection of alpha-methyl 5-HT (5-HT2-receptor agonist) and 5-HT into ear skin produced edema formation more potently than 8-OH-DPAT (5-HT1A agonist) and 2-methyl 5-HT (5-HT3 agonist). 5-HT2 antagonists markedly suppressed the edema response to 5-HT and its receptor agonists, whereas any antagonist for 5-HT1, 5-HT3 and 5-HT4-receptors had no effect. Furthermore, 5-HT2-receptor antagonists partly prevented ear edema in response to substance P (SP), a putative mediator or capsaicin-induced edema, and compound 48/80, a releaser of vasoactive amines form mast cells. These results suggest that 5-HT released from mast cells is partly involved in the development of capsaicin-induced mouse ear edema via 5-HT2 receptors in the ear skin.
This case report describes a 68-year-old man with Cushing's syndrome due to adrenocorticotropic hormone (ACTH)-independent bilateral adrenocortical macronodular hyperplasia (AIMAH). He was referred to our hospital for evaluation of bilateral enlargement of the adrenal glands found incidentally by computed tomography (CT). He had a ten-year history of hypertension. Although he was normokalemic and did not show Cushingoid features, the diagnosis of ACTH-independent Cushing's syndrome was established by endocrinological examinations. His plasma cortisol showed no diurnal rhythm and was unsuppressible by high-dose (8 mg/day) dexamethasone. Plasma ACTH was undetectable and did not respond to corticotropin-releasing hormone. Excised adrenal glands were markedly enlarged (right 28 g and left 64 g). Macroscopic appearance of the glands showed multiple yellowish nodules typical for AIMAH; microscopic findings were also compatible with AIMAH. The present case indicates that patients with AIMAH sometimes do not show typical Cushingoid features and therefore AIMAH can be found incidentally from ultrasound or CT examination of the abdomen.
A 64-year-old woman developed multiple brain abscesses of the basal ganglia associated with Klebsiella pneumoniae septicemia. Magnetic resonance (MR) images showed three different stages of the brain abscesses. The images of early cerebritis of this site mimicked lacunar infarctions or dilated Virchow-Robin spaces. The differentiation of the brain abscess from lacunae and dilated Virchow-Robin spaces is discussed, together with the evolution of the brain abscesses on MR images.
The autopsy of a 28-year-old Japanese male patient, which revealed immature teratoma combined with choriocarcinoma in the mediastinum, is presented. The tumor, which was removed after chemotherapy, was localized in the superior-anterior mediastinum. Chemotherapy was performed several times after operation. However, HCG increased again, and a roentgenogram revealed metastatic shadows in both lungs. The metastatic tumors in the lungs showed only the choriocarcinoma.
A transcutaneous blood glucose monitoring system consists of an ion-sensitive field-effect transistor (ISFET) glucose sensor unit and a suction effusion fluid (SEF) collecting unit. The SEF is directly collected by a weak suction (400 mmHg absolute pressure) through the skin from which the corneum layer of the epidermis has been previously removed. An ISFET glucose sensor unit is able to measure glucose concentrations in a microliter order sampling volume. The system was applied to three diabetic patients during a 75 g oral glucose tolerance test for monitoring blood glucose levels. During the experiments, glucose changes in the SEF followed actual blood glucose levels with 10 min delays. Results suggest the feasibility of utilizing quasi-continuous, transcutaneous blood glucose monitoring for individual patients with various diabetic histories or diabetic complications.
A 62-year-old asymptomatic woman had a nodular shadow approximately 3 cm in diameter in the middle lung field on chest roentgenogram. The shadow gradually grew over 1.5 years. She was then admitted to our hospital for evaluation of the abnormal shadow. Transbronchial biopsy specimens showed a diffuse, small, lymphoid infiltrate with predominance of B-cells. These findings suggested neoplastic proliferation. Further examinations revealed the presence of Sjögren's syndrome. Four months later, she was readmitted for surgical resection. Chest roentgenogram on the second admission disclosed that the mass shadow had shrunk slightly. Histopathological examination of the resected specimen led to the diagnosis of malignant lymphoma, diffuse small cell type (IgG kappa type). Gene analysis revealed the presence of heavy chain gene rearrangements, which confirmed the diagnosis of B-cell lymphoma. In this case, no contraction or necrosis of the lesion was observed, and the change in the shadow size was probably due to partial or transient spontaneous regression.
A 59-year-old man was admitted to the hospital because of dyspnea, fever, and general erythema. He had hypoxemia on admission. Chest X-ray film showed diffuse reticulonodular shadows in both lungs. Chest CT showed a diffuse increase in density, predominantly in both lower lobes. The respiratory failure had rapidly progressed, and the patient died only 40 hours after admission. Autopsy revealed diffuse alveolar damage in the lung, and Aschoff's bodies in the cardiac muscle. Aschoff's bodies are specific for rheumatic fever, and consist of Aschoff's cells with owl-eye-like or caterpillar-like nuclei. We diagnosed this patient's condition as rheumatic fever because of the presence of Aschoff's bodies. Rheumatic fever is generally seen as a disease of younger people, and these patients rarely present with respiratory signs, but this case shows that we have to recognize the possibility of rheumatic fever in adults with respiratory signs and skin lesions.
A 29-year-old man was referred to our hospital because of exertional dyspnea and progressive eruption on the buttocks and the lower extremities. Chest roentgenograms and computed tomograms taken at that time revealed diffuse fibrotic changes accompanied by multiple cavities and bullae in the lungs. There were no signs of mediastinal or hilar lymphadenopathy. A chest roentgenogram taken 7 years before admission showed no abnormalities. Serum ACE and lysozyme levels were high: 29.9 IU/l and 14.1 micrograms/ml, respectively. 67Ga scintigraphy showed diffuse uptake in both lung fields. The PPD skin test was negative, and repeated sputum smears and cultures were negative for pyogenic bacteria and acid-fast bacilli. Examination of transbronchial lung biopsy and skin biopsy specimens confirmed the diagnosis--they showed noncaseating epithelioid granulomas with giant cells and a negative reaction of the stain to acid-fast bacilli, which are compatible with sarcoidosis. The patient was given 30 mg/d of prednisone orally. The dyspnea and eruption were clearly alleviated, although there was little roentgenographic regression of cystic or fibrotic changes. There have been only a few reports of cystic and fibrotic changes early in the course of sarcoidosis. The cystic lesions in this case were probably secondary pulmonary cavities caused by the contracting and obstructive changes related to pulmonary fibrosis.
The secretion of parathyroid hormone (PTH) is influenced by various factors, but extracellular calcium concentration ([Ca2+]e) is the sole factor established to be the physiological regulator. [Ca2+]e acts on Ca2+ sensing receptor recently cloned, and elevates intracellular calcium ([Ca2+]i) and inositol trisphosphate. Although the changes in cAMP level and C-kinase activity also have been demonstrated, the mediator directly operating secretory mechanism of PTH has not been defined. Recently, the activity of chromogranin A-related peptides to modulate PTH secretion was found and their role as the autocrine-paracrine regulator of PTH secretion has been proposed.
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