February 2004
Human Metapneumovirus (hMPV) An Important New Respiratory Virus
Respiratory syncytial
virus (RSV), parainfluenza virus, adenovirus, and
influenzavirus are common known causes of lower
respiratory tract disease in infants and children. Nevertheless, in
a substantial portion of lower respiratory tract infections in
children, no virus can be cultured. In 2001, researchers in the
Human Metapneumovirus
and Lower Respiratory Tract Disease in Otherwise Healthy Infants and Children
John V. Williams, M.D., Paul A.
Harris, Ph.D., Sharon J. Tollefson, et al
Background: Authors sought
to determine the role of human metapneumovirus in
lower respiratory tract illness in previously healthy infants and
children.
Methods: Authors tested
nasal-wash specimens, obtained over a 25-year period from otherwise
healthy children presenting with acute respiratory tract illness,
for human metapneumovirus.
Results: A viral cause other than human metapneumovirus was determined for 279 of 687 visits for acute lower respiratory tract illness (41 percent) by 463 children in a population of 2009 infants and children prospectively seen from 1976 to 2001. There were 408 visits for lower respiratory tract illness by 321 children for which no cause was identified. Of these 321 children, specimens from 248 were available. Forty-nine of these 248 specimens (20 percent) contained human metapneumovirus RNA or viable virus. Thus, 20 percent of all previously virus-negative lower respiratory tract illnesses were attributable to human metapneumovirus, which means that 12 percent of all lower respiratory tract illnesses in this cohort were most likely due to this virus. The mean age of human metapneumovirusinfected children was 11.6 months, the male:female ratio was 1.8:1, and the hospitalization rate was 2 percent. .
Conclusions: Human metapneumovirus infection is a leading cause of respiratory tract infection in the first years of life, with a spectrum of disease similar to that of respiratory syncytial virus
N Engl J Med 350: 443-450, 2004
Human papillomavirus DNA in sera
of cervical cancer patients as
tumor marker
Widschwendter A, Blassnig A, Wiedemair A et al
Persistent infection with human papillomavirus (HPV) has been widely recognized to induce carcinoma of the uterine cervix. Viral DNA has been documented to occur as tumor DNA in the circulation of patients with primary tumors caused by viral infection. The aim of this study was to evaluate the utility of serum HPV DNA as tumor marker in cervical cancer patients. Sera taken from 94 cervical cancer patients at the date of diagnosis and follow-up serum samples from 24 patients were examined for HPV DNA using PCR enzyme immunoassay. Serum samples taken at the date of diagnosis were HPV DNA positive in 45% of all investigated samples. Sera which were HPV DNA positive at the time of diagnosis became and also remained negative after primary treatment in patients without recurrence or persistent disease. HPV DNA was positive up
to 423 days before the time of clinical
diagnosis of recurrence in 10 out of 13 cases (median 72 days, range 0-423
days). Serum HPV DNA seems to reflect biological activity of the tumor. The
results indicate that serum HPV DNA might be a useful additional marker for
early detection of recurrence in cervical cancer patients.
Cancer Lett. 2003 Dec 30; 202(2): 231-9.
Histopathology
and tumor markers
[Article in
Japanese]
Kijima H, Ueyama Y, Osamura
Y.
Serum tumor markers are useful for detection and diagnosis of cancer. Recent
advances in cellular and molecular biology have developed procedures of immunohistochemistry including high sensitivity staining
and epitope retrieval. Using the immunohistochemical
analyses, we can detect various tumor markers, i.e., not only serum tumor
markers (serum protein, carbohydrates), but also cellular skeletons, lymphocyte
surface antigens, cytoplasmic markers, oncogene products and cell adhesion molecules. This article
focuses on several immunohistochemical tumor markers.
Carcinoembryonic antigen(CEA)
is one of the good markers of colorectal cancer. Recent studies have
demonstrated that CEA may function as a metastatic potentiator by different pathway, such as modulation of
immune responses, facilitation of intercellular adhesion and cellular
migration. CA19-9 (sialyl Le antigen), a member of a
family of high molecular weight glycoproteins, was
originally described as a gastrointestinal- and pancreatic-specific tumor
marker. Recent studies have demonstrated that sialyl
Le is a ligand for E-selectin
and may play an important role in tumor metastasis. Stromal
immunoreactivities of CEA or CA19-9 were correlated
with lymph node metastasis and/or vascular invasion. p53
is one of the most important tumor suppressor genes, and the p53 gene product
is known to regulate cell growth and proliferation. Mutation of the p53 gene
can be detected immunohistochemically as overexpression of its protein in the nucleus. Diffuse p53 immunoreactivity was a histological marker of adenocarcinoma. In conclusion, immunohistochemical
tumor markers are useful for histopathological
diagnosis and can be prognostic predictors of cancer.
Rinsho Byori. 2003 Dec; 51(12): 1203-15.
Cerebrospinal
Fluid Abnormalities in Patients with Syphilis: Association with Clinical and
Laboratory Features
Christina M. Marra, Clare L. Maxwell, Stacy L.
Smith et al
Objective: To define clinical and laboratory features
that identify patients with neurosyphilis.
Methods: Subjects (n = 326) with syphilis but
no previous neurosyphilis who met 1993 Centers for
Disease Control and Prevention criteria for lumbar puncture underwent standardized history, neurological examination, venipuncture, and lumbar puncture. Neurosyphilis
was defined as a cerebrospinal fluid (CSF) white blood cell count >20 cells/
L or reactive CSF Venereal Disease Research Laboratory (VDRL) test result.
Results: Sixty-five subjects (20.1%) had neurosyphilis. Early syphilis increased the odds of neurosyphilis in univariate but
not multivariate analyses. In multivariate analyses, serum rapid plasma reagin (RPR) titer
Conclusion: Serum RPR titer helps predict
the likelihood of neurosyphilis. HIV-induced immune
impairment may increase the risk of neurosyphilis.
J Infect Dis 189:369-376, 2004
Minor troponin T elevations predict adverse CV events
Researchers at Johns Hopkins
Medical Institutions in
Charles Henrikson
and colleagues examined the prognostic value of marginal troponin
T among 428 patients presenting with suspected myocardial ischemia to the
emergency department at
They found that 299 patients
had undetectable troponin T levels (<0.01 g/l), 76 had marginal elevations (0.01-0.09 g/l), and 53 had "frankly elevated" levels
(=0.1 g/l).
Patients with marginal or
overtly elevated levels were older, and more likely to be men, but did not
differ from patients with undetectable troponin levels
with respect to the prevalence of coronary artery disease risk factors, history
of coronary disease, or race.
Four months after discharge, Henrikson and team found that patients with marginal troponin levels had a significantly increased rate of combined
death, myocardial infarction (MI), and revascularization compared with
participants who had undetectable levels (p=0.004).
For each individual endpoint,
there was a trend towards increased risk in patients with marginal troponin T levels, although this did not reach statistical
significance.
As with previous studies, the researchers
note that patients with frankly elevated troponin T
levels had a high rate of death/recurrent MI/revascularization (p<0.0001
compared with marginal and normal groups).
The team concludes: "This study shows that patients with chest pain with marginal troponin T elevations are at increased risk of adverse outcomes, and thus worthy of further study to more clearly define their risk profile and optimal treatment strategies."
American Journal of Cardiology; 2004, 93: 275-279
Serodiagnosis of infectious
diseases with
antigen microarrays
sT. Bacarese-Hamilton,
L. Mezzasoma, A. Ardizzoni,
et al
Aims: To generate protein microarrays by printing microbial antigens on slides to enable
the simultaneous determination in human sera of antibodies directed against Toxoplasma gondii,
rubella virus, cytomegalovirus and herpes simplex
virus (HSV) types 1 and 2.
Methods and
Results: Antigens were printed on activated glass
slides using high-speed robotics. The slides were incubated with serum samples
and subsequently with fluorescently labelled
secondary antibodies. Human IgG and IgM bound to the printed antigens were detected using confocal scanning microscopy and quantified with internal calibration
curves. The microarray assay could detect as little
as 05 pg of both IgG and IgM
bound onto the glass surface. Precision profiles ranged from 17 to 185% for
all the antigens. Microarrays and commercial ELISAs were utilized to detect serum antibodies against the
ToRCH antigens in a panel of characterized human
sera. Overall >80% concordance was obtained between microarray
and ELISA kits in the classification of sera.
Conclusions: These results indicate that the microarray is
a suitable assay format for the serodiagnosis of
infectious diseases.
Significance
and Impact of Study: Antigen microarrays
can be optimized for clinical use, their performance is equivalent to ELISA but
they offer significant advantages in throughput, convenience and cost.
Journal of Applied Microbiology 96:1-10, 2004
A Note on Microarrays
Microarray technique
The microarray is a new microhybridisation based assay, which encodes as many as 20000 genes, offers the opportunity to make a parallel hybridization of thousands different genes simultaneously, and thus provides unprecedented resolution for relatively unbiased genetic profiling. In analogy to hybridisation assays, it involves a microfilter or chip made of a porous membrane or materials such as glass, plastic, silicon, gold, or gel, in which either oligonucleotides or cDNA fragments are spotted or synthesised at high density (for example, 10 000 per cm2). Probes for the microarray can be complementary DNA (cDNA), RNA, genomic DNA, or plasmid libraries, which are appropriately labelled and hybridised to the chip. To measure the resulting hybridisation signals, radioactive and fluorescence detection strategies are used. The result is an image obtained by fluorescence scanner or phosphorimager and that can be processed with computer software to generate a spreadsheet of gene expression values. The application of multiple types of statistical analysis to microarray data allows classification and clustering of genes according to their upregulation or downregulation. In principle, data can be linked to expression values to define a list of genes. Furthermore, microarrays also can be used to analyse genomic DNA rather than mRNA, to characterise the interactions of proteins, and potentially to characterise other types of molecule with double stranded DNA.