Human papillomavirus in oesophageal squamous cell carcinoma.

Thirty seven cases of oesophageal squamous cell carcinoma were studied by applying DNA slot blot analysis and in situ hybridisation using type specific probes for HPV 6, 11, 16 and 18. Cases of condyloma accuminata, cervical carcinoma, and laryngeal papilloma were used as controls. Blocks including areas of invasive carcinoma, intraepithelial neoplasia, and normal epithelium were studied in each case. No HPV genome was detectable in any of the oesophageal cases. It is concluded that these types of HPV do not have an association with oesophageal squamous cell carcinoma.     

Prospective study of community-acquired rotavirus infection.

We determined titers of group A rotavirus common antibodies and neutralizing antibodies against serotypes 1 to 4 of prototype human rotavirus (HRV) in cord blood and serum specimens obtained from 38 infants at 4-month intervals from birth until 2 years of age. Nineteen of the infants developed one episode of HRV diarrhea each, and they were matched by age and birth weight with the other 19 infants, who did not develop HRV diarrhea during the follow-up period. We estimated the incidence rate of HRV infection for the two groups of infants combined to be a minimum of 1.34 episodes per infant per year, which is 22 times more common than the occurrence of overt disease caused by the virus in this community. The infection occurred constantly throughout the first 2 years of infancy, whereas all but one of the 19 episodes of overt disease occurred before 12 months of age. Seven of these overt episodes were preceded by at least one episode of subclinical infection earlier, and the other seven were probably due to primary HRV infection. The remaining five episodes occurred before 4 months of age, so that we could not ascertain whether they were due to primary infections because of the presence of maternal antibodies. We showed that levels of HRV antibodies in serum specimens obtained before clinical onset of diarrhea varied widely, and, for most infants in the diarrheal group, levels of these antibodies were similar to those in the serum specimens obtained at the same times from the corresponding age- and birth weight-matched control infants. Nevertheless, the age at which overt disease caused by HRV was most prevalent coincided with the time when the maternal antibodies had declined to low levels but the infants had not yet acquired high titers of these antibodies in their sera.     

Persistent infection of SARS coronavirus in colonic cells in vitro

Severe acute respiratory syndrome coronavirus (SARS-CoV) can produce gastrointestinal symptoms. The intestinal tract is the only extrapulmonary site where viable viruses have been detected. This study examined seven established human intestinal cell lines, DLD-1, HCT-116, HT-29, LoVo, LS-180, SW-480 and SW-620, for their permissiveness to SARS-CoV infection. The results showed that only LoVo cells were permissive to SARS-CoV infection as evident by positive findings from indirect immunofluorescence staining for intracellular viral antigens, in situ hybridization for intracellular viral RNA, and electron microscopy for intracellular viral particles. In contrast to Vero cells, SARS-CoV did not produce cytopathic effects on LoVo cells. However, LoVo cells were found to be highly permissive for productive infection with a high viral titre (>3 x 10(7) viral copies/ml) produced in culture supernatant following a few days of incubation. SARS-CoV established a stable persistent chronic infection that could be maintained after multiple passages. Being a cell line of human origin, LoVo cells could be a useful in vitro model for studying the biology and persistent infection of SARS-CoV. Our results on the expression of angiotensin-converting enzyme 2 (ACE2), a recently identified cellular receptor for SARS-CoV, in these cell lines indicated that it might not be the sole determinant for cells to be susceptible to SARS-CoV infection.     

Noradrenergic neuronal development is impaired by mutation of the proneural HASH-1 gene in congenital central hypoventilation syndrome (Ondine's curse)

Congenital central hypoventilation syndrome (CCHS, Ondine's curse) is a rare disorder of the chemical control of breathing. It is frequently associated with a broad spectrum of dysautonomic symptoms, suggesting the involvement of genes widely expressed in the autonomic nervous system. In particular, the HASH-1-PHOX2A-PHOX2B developmental cascade was proposed as a candidate pathway because it controls the development of neurons with a definitive or transient noradrenergic phenotype, upstream from the RET receptor tyrosine kinase and tyrosine hydroxylase. We recently showed that PHOX2B is the major CCHS locus, whose mutation accounts for 60% of cases. We also studied the proneural HASH-1 gene and identified a heterozygous nucleotide substitution in three CCHS patients. To analyze the functional consequences of HASH-1 mutations, we developed an in vitro model of noradrenergic differentiation in neuronal progenitors derived from the mouse vagal neural crest, reproducing in vitro the HASH-PHOX-RET pathway. All HASH-1 mutant alleles impaired noradrenergic neuronal development, when overexpressed from adenoviral constructs. Thus, HASH-1 mutations may contribute to the CCHS phenotype in rare cases, consistent with the view that the abnormal chemical control of breathing observed in CCHS patients is due to the impairment of noradrenergic neurons during early steps of brainstem development.     

Computer modelling of the organs of the upper abdominal cavity

Method of creation computer models of upper floor of abdomen organs: liver, gallbladder, duodenum, pancreas, stomach, blood vessels with using computer system "DUCT" was described. Details of modelled structures of the cylindric and complicated forms were noted.     

Bilateral simultaneous tubal sextuplets: pregnancy after in-vitro fertilization--embryo transfer following salpingectomy

The presence of a damaged tube has been suggested in recent studies to have a negative effect on in-vitro fertilization (IVF) outcome. Performing bilateral salpingectomy prior to IVF to maximize pregnancy rates may also result in unnecessary surgery. This case is also an example of the occurrence of interstitial pregnancy after salpingectomy. This unusual type of ectopic pregnancy must be kept in mind when evaluating a patient suspected of a possible early abnormal gestation after assisted reproductive technolologies.      

Congenital infection by human cytomegalovirus with a 65 bp deletion in the morphological transforming region II

Summary Human cytomegalovirus (HCMV) infection is an important cause of neonatal death. Using primers derived from sequences within the morphological transforming region II (mtrII), HCMV DNA was amplified by polymerase chain reaction (PCR) from fixed tissues of infants who had died of congenital HCMV infection. In one neonate, HCMV DNA with reduction in the expected size was detected in the liver, spleen, kidney, adrenal, und thyroid tissues by gel electrophoresis. Nucleotide sequencing of the PCR product revealed a 65bp frame-shift deletion within the 79 amino acid open reading frame (ORF) of themtrII. Based upon this observation, it is likely that viral genomic rearrangement involving themtrII may occur in some cases of congenital HCMV infection.     

Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS)

BACKGROUND: Severe acute respiratory syndrome (SARS) became a worldwide outbreak with a mortality of 9.2%. This new human emergent infectious disease is dominated by severe lower respiratory illness and is aetiologically linked to a new coronavirus (SARS-CoV). METHODS: Pulmonary pathology and clinical correlates were investigated in seven patients who died of SARS in whom there was a strong epidemiological link. Investigations include a review of clinical features, morphological assessment, histochemical and immunohistochemical stainings, ultrastructural study, and virological investigations in postmortem tissue. RESULTS: Positive viral culture for coronavirus was detected in most premortem nasopharyngeal aspirate specimens (five of six) and postmortem lung tissues (two of seven). Viral particles, consistent with coronavirus, could be detected in lung pneumocytes in most of the patients. These features suggested that pneumocytes are probably the primary target of infection. The pathological features were dominated by diffuse alveolar damage, with the presence of multinucleated pneumocytes. Fibrogranulation tissue proliferation in small airways and airspaces (bronchiolitis obliterans organising pneumonia-like lesions) in subpleural locations was also seen in some patients. CONCLUSIONS: Viable SARS-CoV could be isolated from postmortem tissues. Postmortem examination allows tissue to be sampled for virological investigations and ultrastructural examination, and when coupled with the appropriate lung morphological changes, is valuable to confirm the diagnosis of SARS-CoV, particularly in clinically unapparent or suspicious but unconfirmed cases.     

Drug resistance mutations and newly recognized treatment-related substitutions in the HIV-1 protease gene: prevalence and associations with drug exposure and real or virtual phenotypic resistance to protease inhibitors in two clinical cohorts of antiretroviral experienced patients

This study aimed at identifying HIV-1 protease amino acid changes associated with protease inhibitor (PI) exposure and susceptibility. New amino acid substitutions were correlated with the number of experienced PIs, reaching statistical significance only for those at positions 3, 44, and 74. The correspondence multivariate model demonstrated that > or =3 experienced PIs and substitutions or mutations at positions 3, 46, 54, 73, 74, and 84 were correlated with PI cross-resistance, including resistance for lopinavir and amprenavir in this cohort of patients who were naive for these drugs.     

Factors associated with successful referral for clinical care of drug users with chronic hepatitis C who have or are at risk for HIV infection

The objective of this study was to determine outcomes of referring drug users (DUs) with chronic hepatitis C for clinical evaluation and care. Two hundred twenty-eight persons with detectable hepatitis C virus RNA were given expedited referrals for evaluation and possible treatment of hepatitis C from a prospective study cohort of current and former opiate-addicted DUs. Four outcomes were analyzed: accepted referral, arrived for clinical evaluation, had liver biopsy, and received treatment. One hundred twenty-seven participants (56%) accepted referral, of whom 54 (43%) arrived for evaluation. Of these participants, 12 (22%) had liver biopsy, and 4 (7%) were treated. Multivariate logistic regression revealed that HIV-infected DUs were significantly less likely to accept referral (adjusted odds ratio [O(Radj)], 0.51; 95% confidence interval [CI], 0.30-0.88), and older participants were more likely to keep an appointment (O(Radj), 1.06/y; 95% CI, 1.00-1.12). Of HIV-seropositive participants, those with a history of injection were more likely to accept referral (O(Radj), 3.60; 95% CI, 1.08-11.96), and those with higher HIV load (O(Radj), 0.50/log10; 95% CI, 0.26-0.94) and Hispanic ethnicity (O(Radj), 0.26; 95% CI, 0.07-0.89) were less likely to keep an appointment. Despite expedited referrals for hepatitis C care, only a few participants received an evaluation, and even far fewer were treated. Because increasingly effective treatment is available, better methods are urgently needed to improve evaluation and treatment of HCV-infected DUs, including those coinfected with HIV.