Cytomegalovirus infection and wheezing in infants

Background: Bronchial asthma‐like symptoms such as wheezing are commonly associated with respiratory tract infection including respiratory syncytial virus (RSV) infection in infants. No study on the association of wheezing with cytomegalovirus (CMV) infection in infancy has been reported, although CMV infection has been observed to play some role in prolonged and intractable wheezing in limited cases. Methods: The present study investigated 40 hospitalized infants who presented with first‐episode wheezing between October 2003 and September 2004. Nasopharyngeal aspirates were tested for RSV, and serum antibodies against CMV were measured. As controls, age‐matched infants with no wheezing were examined for CMV serostatus. Results: RSV‐antigen was detected in 21 subjects (53%), and seven (18%) were considered primary CMV infection serologically. Primary CMV infection was found more often in the wheezers than in the controls although the difference was not statistically significant (P = 0.06). The incidence of splenomegaly was significantly higher in wheezers with CMV infection (86%) than in those with RSV infection or without either infection. The duration of wheezing, fever, and radiographic and laboratory findings during hospitalization were not significantly different. Conclusions: CMV infection based on serologic diagnosis should be considered in infants with first wheezing episode and particularly those with splenomegaly.     

A case of recurrent bacterial meningitis by delayed cerebrospinal fluid (CSF) leakage due to a head trauma]

A 42-year-old man was admitted due to recurrent bacterial meningitis, as he had been treated here for bacterial meningitis three years prior to the current event. He had a remote history of head injury that he had almost forgotten, and his laboratory data showed no immunodeficiency state. 111In-DTPA cisternography showed an abnormal radioactive accumulation in the frontal lobe adjacent to the left frontal sinus at 23 hours after intrathecal injection, and MPR CT images revealed the left frontal sinus bone fracture. These findings indicated that he had a head injury by which a delayed CSF fistula has been formed. He was surgically treated for a CSF leakage. Although a combination therapy of ABPC and CTRX was efficacious for this patient, this regimen may not be ideal, as meningitis by PRSP has been increasing in incidence. Pneumococcal meningitis, once not a difficult infection to treat, could be a difficult one, as resistant strains to ABPC and CTRX have been more common.     

Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer: At which step of multistage carcinogenesis?

We investigated the role of human leukocyte antigen (HLA) class II alleles in multistage cervical carcinogenesis. Cross‐sectional analysis for HLA association with cervical cancer included 1253 Japanese women: normal cytology (NL, n = 341), cervical intraepithelial neoplasia grade 1 (CIN1, n = 505), CIN grade 2 or 3 (CIN2/3, n = 96), or invasive cervical cancer (ICC, n = 311). The HLA class II allele frequencies were compared by Fisher's exact test or the χ²‐test. The Bonferroni adjustment corrected for multiple comparisons. Among the study subjects, 454 women with low‐grade squamous intraepithelial lesion cytology were prospectively monitored by cytology and colposcopy every 3–4 months to analyze cumulative risk of CIN3 within the next 10 years in relation to HLA class II alleles. HLA class II DRB1*1302 allele frequency was similar between women with NL (11.7%) and CIN1 (11.9%), but significantly decreased to 5.2% for CIN2/3 and 5.8% for ICC (P = 0.0003). Correction for multiple testing did not change this finding. In women with low‐grade squamous intraepithelial lesion cytology, the cumulative risk of CIN3 diagnosed within 10 years was significantly reduced among DRB1*1302‐positive women (3.2% vs. 23.7%, P = 0.03). In conclusion, the two different types of analysis in this single study showed the protective effect of the DRB1*1302 allele against progression from CIN1 to CIN2/3.     

Moxifloxacin resistance and genotyping of Mycobacterium avium and Mycobacterium intracellulare isolates in Japan

BackgroundAlthough fluoroquinolones are considered as alternative therapies of pulmonary Mycobacterium avium complex (MAC) disease, the association between fluoroquinolone resistance and MAC genotypes in clinical isolates from individuals not previously treated for MAC infection is not fully clear.MethodsTotals of 154 M. avium isolates and 35 Mycobacterium intracellulare isolates were obtained from treatment-naïve patients with pulmonary MAC disease at the diagnosis of MAC infection at 8 hospitals in Japan. Their susceptibilities of moxifloxacin were determined by broth microdilution methods. Moxifloxacin-resistant isolates were examined for mutations of gyrA and gyrB. Variable numbers of tandem repeats (VNTR) assay was performed using 15 M. avium VNTR loci and 16 M. intracellulare VNTR loci.ResultsMoxifloxacin susceptibility was categorized as resistant and intermediate for 6.5% and 16.9%, respectively, of M. avium isolates and 8.6% and 17.1% of M. intracellulare isolates. Although the isolates of both species had amino acid substitutions of Thr 96 and Thr 522 at the sites corresponding to Ser 95 in the M. tuberculosis GyrA and Gly 520 in the M. tuberculosis GyrB, respectively, these substitutions were observed irrespective of susceptibility and did not confer resistance. The VNTR assays showed revealed three clusters among M. avium isolates and two clusters among M. intracellulare isolates. No significant differences in moxifloxacin resistance were observed among these clusters.ConclusionsAlthough resistance or intermediate resistance to moxifloxacin was observed in approximately one-fourth of M. avium and M. intracellulare isolates, this resistance was not associated with mutations in gyrA and gyrB or with VNTR genotypes.     

Molecular cloning of proopiomelanocortin cDNA in the ratfish, a holocephalan

Proopiomelanocortin (POMC) is a precursor for several pituitary hormones including adrenocorticotropin (ACTH), melanocyte-stimulating hormone (MSH) and endorphin (END). Fish POMCs in four taxonomic classes, Cephalaspidomorphi (lampreys), Chondrichthyes (cartilaginous fish), Sarcopterygii (lobe-finned fish), and Actinopterygii (ray-finned fish) have been identified. However, two essential species, ratfish in Chondrichthyes and hagfish in Agnatha, are still missing in the evolutionary image of this molecule. The present study reports analysis of POMC cDNA in the ratfish, Chimaera phantasma, which belongs to another subclass in the Chondrichthyes. Partial cDNA clones were amplified by PCR from single-strand cDNA prepared on total RNA from a complex of pituitary and hypothalamus, and subsequently overlapped to obtain a full-length sequence. Ratfish POMC cDNA consists of 1294bp excluding the poly(A) tail. It encodes a signal peptide of 25 amino acids and POMC of 300 amino acids. gamma-MSH, ACTH, alpha-MSH, delta-MSH, beta-MSH, and beta-END are located at prePOMC (76-87), (120-158), (120-132), (212-227), (275-290), and (293-325), respectively. delta-MSH, originally found in elasmobranch POMCs, was also present in ratfish POMC, suggesting this structure might have appeared after the divergence of chondrichthians from the ancestral lineage. Thus, we demonstrated the common occurrence of four MSHs in chondrichthian POMC and established a clear understanding of the molecular evolution of POMC in gnathostomes.     

Primary liver cancers with nonalcoholic steatohepatitis

Nine patients with hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) (six men and three women, median age 71.5 years) and one patient with intrahepatic cholangiocarcinoma (ICC), a 50-year-old man, in NASH are described. Most patients were associated with obesity, diabetes, hypertension, hypercholesterolemia, or hypertriglyceridemia. Seven patients showed insulin resistance and hyperinsulinemia. All patients except one met the criteria for metabolic syndrome. An HCC or ICC diagnosis was confirmed by tumor biopsy, surgery or autopsy except in two patients, who were diagnosed by computed tomography or hepatic angiography. The underlying liver disease was liver cirrhosis in six patients and chronic liver disease including mild hepatic fibrosis in four patients. The treatment of liver cancers consisted of surgery, radio-frequency ablation (RFA), transcatheter arterial embolization and transcatheter arterial infusion. Although the follow-up period was relatively short (median 27.5 months, average 32.1 months), all postoperative and post-RFA patients have not had a recurrence of HCC to date, except for one patient who had a palliative operation with intra-arterial infusion of anticancer drugs through an implanted reservoir port. Older age and liver cirrhosis are considered risk factors for HCC in NASH, and regular screening of these patients is necessary. Diabetes may contribute to the development of ICC in NASH. Curative therapy (surgery or RFA) and weight loss by the active therapeutic intervention (nutritional care and exercise therapy) after curative therapy may help us improve the prognosis of HCC in NASH.     

Proposed criteria for mixed-dust pneumoconiosis: definition, descriptions, and guidelines for pathologic diagnosis and clinical correlation

We defined mixed-dust pneumoconiosis (MDP) pathologically as a pneumoconiosis showing dust macules or mixed-dust fibrotic nodules (MDF), with or without silicotic nodules (SN), in an individual with a history of exposure to mixed dust. We defined the latter arbitrarily as a mixture of crystalline silica and nonfibrous silicates. According to our definition of MDP, therefore, MDF should outnumber SN in the lung to make a pathologic diagnosis of MDP. In the absence of confirmation of exposure, mineralogic analyses can be used to support the pathologic diagnosis. The clinical diagnosis of MDP requires the exclusion of other well-defined pneumoconioses, including asbestosis, coal workers’ pneumoconiosis, silicosis, hematite miners’ pneumoconiosis, welders’ pneumoconiosis, berylliosis, hard metal disease, silicate pneumoconiosis, diatomaceous earth pneumoconiosis, carborundum pneumoconiosis, and corundum pneumoconiosis. Typical occupations associated with the diagnosis of MDP include metal miners, quarry workers, foundry workers, pottery and ceramics workers, and stonemasons. Irregular opacities are the major radiographic findings in MDP (ILO 1980), in contrast to silicosis, in which small rounded opacities predominate. Clinical symptoms of MDP are nonspecific. MDP must be distinguished from a variety of nonoccupational interstitial pulmonary disorders.     

Etiology and outcome of community-acquired pneumonia in relation to age and severity in hospitalized adult patients]

The aim of this study was to determine the etiology and outcome of community-acquired pneumonia (CAP) in relation to age and severity in hospitalized patients. Overall, 652 consecutive patients with CAP were studied retrospectively during a 4-year period from 2002. Severity of pneumonia was classified according to the guidelines of the Japanese Respiratory Society (JRS 2005) and American Thoracic Society (ATS 2001). The etiology was identified in 401 of 652 (61.5%) cases. The four most frequent pathogens were Streptococcus pneumoniae (26.2%), influenza virus (12.4%), Mycoplasma pneumoniae (10.9%), and Haemophilus influenzae (5.9%). The most common pathogen in the younger (15-44 years) group and very severe patients (JRS) was Mycoplasma pneumoniae (38.4%) and influenza virus (28.6%), respectively. The three most frequent pathogens in severe CAP patients (ATS) were Streptococcus pneumoniae (29.0%), influenza virus (17.4%), and Legionella species (13.0%). The overall mortality was 6.4%. The mortality of CAP patients among aged 1544, 45-64, 65-74, and 75 years or older was 1.4%, 3.3%, 6.9% and 9.3%, respectively. The mortality of mild, moderate, severe, and very severe patients (RS) was 0%, 4.1%, 15.5%, and 53.6%, respectively. The mortality of non-severe and severe patients (ATS) was 1.8% and 23.9%, respectively. Age and severity had influence on the prevalence of the main microbial pathogens. Streptococcus pneumoniae remained the most important pathogen that needs consideration in initial antibiotic therapy in patients with CAP of all ages and severities. Pathogens identified in patients with severe CAP in Japan were similar to those of Western countries, except for the high incidence of the influenza virus.     

Erythema induratum (nodular vasculitis) associated with Crohn's disease: a rare type of metastatic Crohn's disease

We herein report a patient with erythema induratum/nodular vasculitis (EI/NV) associated with Crohn's disease (CD), which is considered to be a rare type of metastatic CD. A 54-year-old woman, who had a history of CD, presented with erythematous nodules on her legs. The histopathological features of the skin biopsy revealed a granulomatous, mixed septal and lobular panniculitis, which was characterized by many discrete epithelioid cell granulomas (necrobiotic/necrotizing-type and sarcoidal type), necrosis of the adipocytes, and granulomatous phlebitis in the muscular wall of a subcutaneous vein. A review of the pertinent literature and the presented case suggested the following: (1) panniculitis associated with CD may be either an erythema nodosum type or an EI/NV type; (2) so far, the reported cases of metastatic CD or granulomatous vasculitis in CD rarely presented with granulomatous panniculitis without dermal involvement, and most cases showed histopathological features that were similar to or indistinguishable from those of EI/NV; and (3) the finding of granulomatous vasculitis (especially the presence of discrete epithelioid cell granulomas involving the veins or venules) may be a characteristic feature of EI/NV associated with CD, in contrast to the finding of acute vasculitis, which is typically present in patients with EI/NV due to causative factors other than CD.     

Genetic aberration on chromosome 10 in human oral squamous cell carcinoma

Recently a tumor suppressor gene, a deleted in malignant brain tumor gene (DMBT1), was detected on chromosome 10. In some types of tumors, the frequent deletion of DMBT1 locus have been reported as well as loss of heterozygosity (LOH) on chromosome 10. However, little is known relating to human oral squamous cell carcinoma (OSCC). To study the genetic aberrations on chromosome 10 in OSCC, we performed polymerase chain reaction (PCR) analysis of microsatellite polymorphisms corresponding to 16 loci, containing 2 DMBT1 loci. We examined 38 oral primary squamous cell carcinoma (SCC) tissues and corresponding normal tissues. Microsatellite instability (MI) was detected at least on 1 of the 16 loci in 15 (39.5%) of 38 cases, and loss of heterozygosity (LOH) at least 1 of the 16 loci was also observed in 28 (73.7%) of 38 cases. LOH was accumulated at D10S202 (34.6%) and D10S217 (28.6%), suggesting the presence of two putative tumor suppressor genes associated with OSCC. The 2 DMBT1 loci, D10S209 and D10S587, had comparatively high frequent LOH (20.0 and 22.7%, respectively), maybe indicating the important role of DMBT1 in OSCC. No significant correlation between histological differentiation and LOH was found. These results suggest that genetic aberrations on chromosome 10 play important roles in the oncogenesis of OSCC.