Unambiguous identification of <Emphasis Type="Italic">JC polyomavirus</Emphasis> strains transmitted from parents to children

Summary. JC polyomavirus (JCV), the etiological agent of progressive multifocal leukoencephalopathy, is ubiquitous in humans, infecting children asymptomatically, then persisting in renal tissue. It has been proposed that JCV is transmitted mainly from parents to children through long-term cohabitation. The objective of this study was to further elucidate the mode of JCV transmission. In 5 families, we selected parent/child pairs between whom JCV was probably transmitted (judged on the basis of the identity of a 610-bp JCV DNA sequence between the parent and child). We established 5 to 9 complete JCV DNA clones from the urine of each parent or child. The complete sequences of these clones were determined and compared in each family. Nucleotide substitutions were detected in 4 parents and 1 child, and sequence rearrangements (deletions or duplications) were found in 2 parents and 2 children. Phylogenetic comparison of the detected sequences indicated that the diversity of JCV DNA sequences was generated in each family (i.e. not caused by multiple infection). We found that in 4 of the 5 families, a sequence detected in the parent was completely identical to one in the child. These findings provided further support for the proposed mode of JCV transmission, i.e. parent-to-child transmission during cohabitation.     

Gastric medullary carcinoma, a distinct entity associated with microsatellite instability-H, prominent intraepithelial lymphocytes and improved prognosis

AIMS: To determine the clinicopathological and molecular features of gastric medullary cancer. METHODS AND RESULTS: Clinicopathological review and microsatellite instability (MSI) analysis were carried out on 17 gastric medullary and 64 non-medullary cancers. In addition to characteristic histopathology, gastric medullary cancers had certain prominent features: (i) the average survival time was longer in medullary and low-grade non-medullary cancers than in high-grade (P = 0.004); (ii) serosal involvement was less common in medullary cancers (29.4%, 5/17) than in non-medullary cancers (9.4%, 6/64) (P < 0.05) while pushing borders were more common in medullary cancers (70.6%, 12/17 versus 17.2%, 11/64, P = 0); (iii) the presence of intraepithelial lymphocytes (IELs) in medullary and non-medullary cancers was 2380/10 high-power field (HPF) and 147/10 HPF (P = 0), respectively. Both peritumoural infiltrating lymphocytes (pTIL) and a Crohn's-like reaction were more common in medullary cancers than in non-medullary (pTIL 35.3%, 6/17 versus 3.1%, 2/64; a Crohn's-like reaction 70.6%, 12/17 versus 32.8%, 21/64; P < 0.05); (iv) medullary and high-grade non-medullary cancers were more associated with reduced ECD expression in comparison with low-grade cancers (P < 0.05); (v) higher MSI-H (Bat26+) rate was observed in medullary cancers (41.2%, 7/17) than in non-medullary (1.6%, 1/64) (P = 0). CONCLUSIONS: Gastric medullary cancer has distinct clinicopathological features and genetic alterations. Two subtypes of gastric medullary cancers, Bat26+ and Bat26-, might have prognostic implications, thus analysis of Bat26 may be of clinical value.     

Epidemiologic linkage and public health implication of a cluster of severe acute respiratory syndrome in an extended family

Severe acute respiratory syndrome (SARS) is highly contagious. Mandatory home confinement of 10 days has generally been recommended to quarantine close contacts of SARS cases. We report the epidemiologic linkage of SARS within an extended family. The estimated incubation period was beyond 10 days in some of the affected members. One child was identified as the source of SARS transmission to another household.     

Delayed facial palsy after vestibular schwannoma resection: the role of viral reactivation. Our experience in 8 cases

OBJECTIVE: To study the role of herpes virus reactivation in the onset of more than three days-delayed facial paralysis (FP) following vestibular schwannoma (VS) surgery and advocate a specific medical management. MATERIAL AND METHODS: Retrospective study on 8 cases from a series of 348 patients operated on of a VS between 1996 and 2002. Seven of the eight patients were given intravenously acyclovir (30 mg x kg(-1) x d(-1) for 5 days) and methyl-prednisolone (2 mg x kg(-1) x d(-1) for 7 days). A serologic testing looking for specific anti-herpes simplex viruses type 1 and 2 (HSV-2) and varicella-zoster virus (VZV) antibodies at the onset of the FP and 2 weeks later could be done in only 3 cases. RESULTS: Mean delay of FP onset was 8.75 days. Mean time for recovery with intravenous treatment was 90 days. All treated patients had a House and Brackmann grade 1 recovery. The last one had only a grade 3 after 400 days of evolution: he could not be treated because of postoperative transient psychiatric problems. Serologic testing revealed in those patients in whom it could be done either a high level of anti-HSV or -VZV antibodies at the time of onset or a dramatic increase in anti-HSV or anti-VZV antibodies between the two samples, strongly suggesting a HSV or VZV reactivation. CONCLUSION: HSV or VZV reactivation can be evocated in most cases of delayed FPs arising in the postoperative course of VSs, suggesting usefulness of emergency-given steroid and acyclovir intravenous regimen to block virus replication and fight secondary oedema and inflammation causative of nerve lesions. Evoked reactivation mechanism is comparable to that already suspected in delayed FP arising with the same delay in middle ear surgical procedures.     

Regulation of matrix metalloproteinases (MMPS) and their inhibitors (TIMPS) during mouse peri-implantation: role of nitric oxide

Nitric oxide (NO) is believed to play pivotal roles in embryo implantation. The purpose of this study was to investigate the effect of NO on matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), as well as the mechanism of NO during mouse implantation. Nitric oxide synthase (NOS) inhibitor, L-NAME was administered with or without sodium nitroprusside (SNP), NO donor, into one uterine horn on day 3 of pregnancy, and the contralateral uterine horn served as the control. We collected the uteri on days 5, 6, and 7 of pregnancy and examined the mRNA expression of MMP-2, -9, and TIMP-1, -2, -3, as well as the activities of MMP-2 and -9 by using in situ hybridization and gelatin zymography, respectively. The results showed that, compared with the control, the expression of MMP-2 and -9 mRNAs was decreased in L-NAME-treated uteri during peri-implantation. Treatment of mice with L-NAME had slight effect on the expression of TIMP-1 mRNA on day 5 of pregnancy, and no effect on TIMP-2 mRNA expression during peri-implantation. However, the expression of TIMP-3 mRNA was increased. The gelatin zymography results indicated that the activity of MMP-9 was decreased during peri-implantation, but the activity of MMP-2 did not change significantly in these time points examined. The L-NAME-mediated effect on MMPs and TIMPs were significantly reversed when SNP was co-administered with L-NAME. These data suggest that inhibition of NO production regulates the gene expression of MMP-2, -9, and TIMP-3, together with the activity of MMP-9 during peri-implantation, which may have serious consequence on embryo implantation.