Reversible respiratory failure due to rhabdomyolysis associated with cytomegalovirus infection

A 58-year-old woman presented with muscle weakness, whole body myalgia, and dyspnea. On admission, neurological examination showed proximal muscle weakness in the extremities. The weakness gradually extended to the bulbar and respiratory muscles, necessitating an artificial ventilator. Serum CK level was markedly increased (33,774 IU/L; normal <150 IU/L) and myoglobinuria was noted in urinalysis. There was no sign of renal failure. Nerve conduction study was normal, but needle EMG showed myopathic changes in the weak muscles. Serological studies for virus titers showed more than a four-fold increase of cytomegalovirus (CMV) antibody titer during the disease course. The IgM anti-GM2 antibody was also elevated in the acute phase and decreased in the recovery phase. The muscle weakness and respiratory failure gradually improved after intravenous methylprednisolone administration, and the serum CK level was normalized in several days. CMV infection was thought to have played a central role in the rhabdomyolysis, leading to critical but reversible respiratory muscle paralysis.     

Cyp11b1 is induced in the murine gonad by luteinizing hormone/human chorionic gonadotropin and involved in the production of 11-ketotestosterone, a major fish androgen: conservation and evolution of the androgen metabolic pathway

We have shown previously that Cyp11b1, an 11beta-hydroxylase responsible for glucocorticoid biosynthesis in the adrenal gland, was induced by cAMP in androgen-producing Leydig-like cells derived from mesenchymal stem cells. We found that Cyp11b1 was induced in male Leydig cells, or female theca cells, when human chorionic gonadotropin was administered in immature mice. Expression of Cyp11b1 in rodent gonads caused the production of 11-ketotestosterone (11-KT), a major fish androgen, which induces male differentiation or spermatogenesis in fish. As in teleosts, plasma concentrations of 11-KT were elevated in human chorionic gonadotropin-treated mice. In contrast to teleosts, however, plasma concentrations of 11-KT were similar in both sexes, despite levels of testosterone, a precursor substrate, being about 20 times higher in male mice. Because expression of 11beta-hydroxysteroid dehydrogenase type 2, was much higher in the mouse ovary than in the testis, conversion of testosterone into 11-KT may occur more efficiently in the ovary. In a luciferase reporter system that was responsive to and activated by androgens, 11-KT efficiently activated mammalian androgen receptor-mediated transactivation. Our results suggest that the androgen metabolic pathway is conserved between teleosts and mammals, despite sexual dominance and reproductive functions of 11-KT being altered during evolution.     

Circulating immune complexes in patients with mycoplasmal pneumonia

Circulating immune complexes as measured by conglutinin (IgG-IC) and IgM rheumatoid factor (IgM-RF) were studied in 114 patients with mycoplasmal pneumonia (58 inpatients and 56 outpatients). The levels of IgG-IC and IgM-RF of the patients were significantly higher than those of 13 healthy control subjects. In addition, the levels of IgG-IC of the inpatients were significantly higher than those of the outpatients. The highest titers of IgG-IC were obtained 9 to 30 days after onset of disease, and the levels of IgG-IC were elevated during the time period when pulmonary changes were pronounced. The levels of IgM-RF were irrelevant to infiltration on chest radiographs. An analysis using density gradient centrifugation showed that the decrease of IgG-IC with intermediate size was associated with improvement of the disease. A possible pathogenic role of IgG-IC in mycoplasmal pneumonia is discussed.     

Sn-1,2-diacylglycerols and phorbol ester stimulate the production of progesterone from the human placenta

Human term placental explants were used to investigate the possible role of phospholipid-sensitive and Ca2+ dependent protein kinase in the regulation of human placental progesterone production. Placental tissue was incubated with low density lipoprotein as a precursor of progesterone in the presence or the absence of phorbol 12-myristate-13-acetate, 1-oleoyl-2-acetyl-glycerol, and the calcium ionophore A23187. The rate of progesterone production by placental tissue was 21.7 +/- 4.6 ng. (mg wet wt)-1.(2 h)-1 (mean +/- SEM) with 500 mg low density lipoprotein/l (control). The rate of progesterone production was accelerated 2-fold by 1 nmol/l phorbol 12-myristate-13-acetate, 1.6-fold by 250 mumol/l 1-oleoyl-2-acetyl-glycerol and this increase was dose-related (25-250 mumol/l 1-oleoyl-2-acetyl-glycerol). A nonpromoting derivative, 4 alpha-phorbol-12,13-didecanoate had no effect. The phorbol 12-myristate-13-acetate or 1-oleoyl-2-acetyl-glycerol induced stimulation of progesterone production was not associated with a change in the intracellular cAMP level. Addition of 10 mumol/l A23187 further increased progesterone production with 125 mumol/l 1-oleoyl-2-acetyl-glycerol. The rate of progesterone production was accelerated 1.6-fold by 125 mumol/l 1-oleoyl-2-acetyl-glycerol and 10 mumol/l A23187 as compared with control. The effects of the phorbol ester and the diacyl glycerol were completely blocked by the addition of the protein synthesis inhibitor cycloheximide. We conclude that these phorbol regents are able to stimulate human placental progesterone production. The possible roles of intracellular Ca2+ and protein kinase C in placental steroidogenesis are discussed.     

High glucose induces plasminogen activator inhibitor-1 expression through Rho/Rho-kinase-mediated NF-kappaB activation in bovine aortic endothelial cells

Recently, it has become evident that elevated levels of plasminogen activator inhibitor-1 (PAI-1) are associated with myocardial infarction and stroke, especially in patients with diabetes. The molecular mechanisms involved in hyperglycemia-induced PAI-1 expression in bovine aortic endothelial cells (BAEC) were investigated. PAI-1 expression in BAEC was significantly increased in accordance with the concentration of glucose in media from 5.7 mM to 23 mM. Stimulation with high glucose (23 mM) significantly increased small GTPase Rho A activation. Pretreatment with a Rho-kinase inhibitor, Y-27632 (1-10 microM), significantly blocked high glucose-induced PAI-1 expression. NF-kappaB activity determined using the luciferase reporter gene assay was significantly enhanced by high glucose, and pretreatment with Y-27632 inhibited high glucose-induced PAI-1 expression at the basal level. An inhibitor of NF-kappaB action, namely parthenolide (0.1 microM), BAY 11-7082 (5 microM) and SN50 (1 microM), significantly blocked high glucose-mediated PAI-1 expression to a level with low glucose (5.7 mM). These data suggested that high glucose-induced PAI-1 expression in endothelial cells is mediated by NF-kappaB activation through the Rho/Rho-kinase pathway. Inhibition of Rho/Rho-kinase signaling might be a novel target for diabetes and metabolic syndrome.     

Gastrointestinal tract metastasis of lung cancer: The PD-L1 expression and correlated clinicopathological variables

The gastrointestinal tract is a rare site for metastatic lung cancer. Programmed cell death-ligand 1 (PD-L1) expression in lung cancer is a biomarker for the response to anti-PD-1/PD-L1 therapy. We investigated clinicopathological features and PD-L1 expression in 25 gastrointestinal metastatic tumors from the lung and primary adenocarcinoma of the small bowel. The small bowel was the most common site (16/25; 64%) of gastrointestinal tract lung cancer metastasis. A total of 19 (76%) of the gastrointestinal metastasis showed PD-L1 expression in ≥5% of tumor cells, with 14 (56%) showing high expression levels (≥50%). In contrast, 21 (84%) expressed PD-L1 in ≥5% immune cells, including 4 (16%) showing a high expression levels (≥50%). The PD-L1 expression on tumor cells and immune cells in primary lung cancer and corresponding gastrointestinal metastasis was concordant in 13 (68%) and 11 (58%) of the 19 paired cases, respectively. Small-bowel metastasis of lung cancer was characterized by a higher incidence of perforation (31% vs. 0%), ulcerated mass (83% vs. 60%), and neoplastic PD-L1 expression (75% vs. 0%) compared to primary small-bowel adenocarcinoma. Gastrointestinal metastasis from lung cancer might be a potential target for immune checkpoint inhibitor therapy, given its high expression of PD-L1.     

Evaluation of condyle-fossa relationships in adolescents with various skeletal patterns using cone-beam computed tomography

Objectives:To evaluate the condyle-fossa relationship in adolescents with various skeletal patterns using cone-beam computed tomography (CBCT).Materials and Methods:CBCT images obtained in 120 adolescent patients were used for this study. The patients were divided into 3 groups according to 3 criteria: (1) age (early, middle, and late adolescence); (2) facial height ratio or Jarabak quotient (hyperdivergent, normodivergent, and hypodivergent); and (3) ANB classification (Class I, Class II, and Class III). Temporomandibular joint space (TMJS: AS, anterior space; SS, superior space; PS, posterior space; MS, medial space; LS, lateral space), width and depth of the condyle (MLT, mediolateral thickness; APT, anteroposterior thickness), articular slope (ArS) and vertical height of the fossa (VHF) were measured and compared using CBCT.Results:Differences in condyle-fossa relationships were not significantly different between male and female adolescents, but were significantly different (P < .05) between left and right sides. The mean values showed no statistical differences according to age and skeletal pattern. Most measurements in the sagittal view showed that SS was the greatest, and the mean ratio of AS to SS to PS was 1.00 to 1.27 to 1.19, respectively. The mean values of coronal MS and LS were not significantly different.Conclusions:There were almost no statistical differences in the TMJS in adolescents across various factors except between left and right sides.     

The relationship between age and minimum alveolar concentration of sevoflurane for maintaining bispectral index below 50 in children

We evaluated the minimum alveolar concentration of sevoflurane required to maintain the bispectral index below 50 in children. We studied 55 children, divided into 1‐year‐old, 2‐ to 4‐year‐old and 5‐ to 9‐year‐old groups and used Dixon's up‐and‐down method and probit analysis. In the 1‐year‐old group, the bispectral index values remained above 50, with the end‐tidal sevoflurane concentration reaching 4.0% or higher. The minimum alveolar concentration of sevoflurane for maintaining the bispectral index below 50 was significantly higher in the 2‐ to 4‐year‐old group (2.33%, 95% CI 2.25–2.57) than in the 5‐ to 9‐year‐old group (2.10%, 95% CI 1.94–2.25; p = 0.005). We conclude that assessing the depth of anaesthesia using bispectral index is unreliable in children aged < 2 years anaesthetised with sevoflurane.