Persistence of varicella-zoster virus DNA in blood mononuclear cells of patients with varicella or zoster

Varicella-zoster virus (VZV) DNA was detectable by in-situ hybridization in blood mononuclear cells (MNCs) of patients with varicella or zoster for 2–56 days after the onset of a rash. VZV DNA was present in many MNCs from one acute varicella patient 2 days after the onset of the rash and was rarely found in MNCs during acute zoster, convalescent zoster, and convalescent varicella. The morphology of MNCs containing VZV was heterogenous, although most viral-DNA-containing MNCs were large monocytoid cells. Serial examination of blood MNCs from one adult with varicella revealed VZV DNA up until 8 weeks, but not 16 weeks, after the appearance of the rash; parallel studies in four zoster patients showed VZV DNA up until 3 weeks, but not later than 7 weeks after the appearance of the rash. These results indicate that MNCs become infected with VZV during the primary encounter with VZV (varicella) and during reactivation (zoster) and that infection continues for weeks after the onset of the skin rash. Furthermore, the detection of VZV DNA in blood MNCs of uncomplicated zoster patients coincides with the period during which these patients experience pain.     

Influence of hypoxia on wavelength dependence of differential pathlength and near-infrared quantification

Continuous wave near-infrared spectroscopy (NIRS) measurements of cardiac correlated changes in attenuation in the adult human head were computed using a Fourier analysis technique that eliminates the positive error bias associated with the magnitude of the Fourier coefficient. These attenuation changes were used to determine wavelength dependence of differential pathlength, DP(lambda), at four stages during progressive hypoxia (21, 17, 13 and 9% FIO2) in normal volunteers. The effects of incorporating DP(lambda) into NIRS algorithms to compute relative concentration changes and absolute concentration of oxyhaemoglobin and deoxyhaemoglobin are discussed. Because variations in DP(lambda) are restricted to wavelengths below 780 nm, absolute concentration calculations are influenced by hypoxia-induced changes while relative concentrations are unaffected. However, even accounting for changes in DP(lambda) did not allow computation of physiologically reasonable absolute concentrations of the haemoglobin species.     

The mutational spectrum of brachydactyly type C

Growth/differentiation factor-5 (GDF5), also known as cartilage-derived morphogenetic protein-1 (CDMP-1), is a secreted signaling molecule that participates in skeletal morphogenesis. Heterozygous mutations in GDF5, which maps to human chromosome 20, occur in individuals with autosomal dominant brachydactyly type C (BDC). Here we show that BDC is locus homogeneous by reporting a GDF5 frameshift mutation segregating with the phenotype in a family whose trait was initially thought to map to human chromosome 12. We also describe heterozygous mutations in nine additional probands/families with BDC and show nonpenetrance in a mutation carrier. Finally, we show that mutant GDF5 polypeptides containing missense mutations in their active domains do not efficiently form disulfide-linked dimers when expressed in vitro. These data support the hypothesis that BDC results from functional haploinsufficiency for GDF5.     

Mechanisms of action of major-histocompatibility-complex-linked genes affecting reproduction

PROBLEM: To provide insight into the mechanisms of action of the major-histocompatibility-complex (MHC)-linked genes affecting reproduction. METHOD OF STUDY: The data were obtained using a variety of cellular and molecular techniques in experimental animals and from population genetic studies in humans. RESULTS: In the mouse, the preimplantation embryonic development (Ped) locus, whose functional gene is Q9, regulates fast and slow cleavage of the early embryo. There is also evidence for a growth and reproduction complex (Grc)-like region from serologic, molecular, and cytogenetic studies. In the human, the human leukocyte antigen (HLA)-G gene has been associated with an increased rate of embryonic cleavage in those embryos that express the HLA-G antigen. Sharing of HLA antigens in couples has been associated with recurrent spontaneous abortions, gestational trophoblastic tumors, and unexplained infertility. Detailed mapping studies showed that the genes responsible are not the HLA genes themselves, but genes closely linked to the HLA-DR-DQ-B genes. The HLA region genes can interact epistatically with the C3 allele of transferrin to increase the incidence of fetal loss. In the rat, the Grc region, which is closely linked to the MHC, has been associated with embryonic loss, growth defects, and susceptibility to chemical carcinogens. The Grc can interact epistatically with the tail anomaly lethal (Tal) gene or the hood restriction (Hre) gene to enhance these effects. CONCLUSIONS: There are two basic mechanisms for the effects of MHC-linked genes on reproduction and development: individual gene effects (Ped [Q9], HLA-G) and extended genetic effects (MHC-linked genes in the rat [Grc] and in the human). The nature of these genetic effects, particularly the MHC-linked effects, can also provide some insight into the different theories of human origins: These effects are most consistent with the monogenic theory.     

Ramp-function work test suitable for automatic computation

Heart rate (HR) response to step-function and ramp-function (20 W/min) work tests was compared in 12 healthy subjects. For a given power output (P), HR was substantially lower in the ramp tests. The HR difference increased with power output and increasing difference in work time between the test types. The HR difference can be explained in terms of a drift component (which accounts for 1/3 of the difference) and a lag component (2/3). As a consequence of the HR differences, P for a given HR is higher in ramp tests. Work capacity expressed, for example as P170, can be determined in ramp tests, and the result can be translated to step-function P170. The precision in this translation is markedly improved if a steady-state period is incorporated into the ramp test.     

Radiation-related cytological changes in oral malignant cells

Carcinoma of the oral cavity constitutes approximately 40% of overall malignant tumours in India, with an incidence of about 56,000 cases per year. Radiation responses in oral cancer cells by cytology have not been extensively studied. 102 patients with squamous cell carcinoma of the oral cavity treated by fractionated radiotherapy were studied. Serial scrape smears were taken from each tumour before and after irradiation. The abnormal nuclear counts per 1000 malignant cells were 1.6 and 14.1(p<0.001) for micronucleation, 0.9 and 5.5 (p<0.001) for nuclear budding, 7.6 and 28.1(p<0.001) for binucleation and 2.4 and 11.7(p<0.001) for multinucleation respectively. The study showed a significant rise in radiation induced cytological responses. In addition, radiation changes observed included abnormal and incomplete divisions of a nucleus, fibroblast like appearance cells, and enlargement of nuclear size as well as cytoplasmic granulation. These changes may have an important role to play in understanding the mechanism of cell killing after radiotherapy.     

Fast Adaptive Unsharp Masking with Programmable Mediaprocessors

Unsharp masking is a widely used image-enhancement method in medical imaging. Hardware-based solutions can be developed to support high computational demand for unsharp masking, but they suffer from limited flexibility. Software solutions can easily incorporate new features and modify key parameters, such as filtering kernel size, but they have not been able to meet the fast computing requirement. Modern programmable mediaprocessors can meet both fast computing and flexibility requirements, which will benefit medical image computing. In this article, we present fast adaptive unsharp masking on two leading mediaprocessors or high-end digital signal processors, Hitachi/Equator Technologies MAP-CA and Texas Instruments TMS320C64x. For a 2k × 2k 16-bit image, our adaptive unsharp masking with a 201 × 201 boxcar kernel takes 225 ms on a 300-MHz MAP-CA and 74 ms on a 600-MHz TMS320C64x. This fast unsharp masking enables technologists and/or physicians to adjust parameters interactively for optimal quality assurance and image viewing.     

Stage, survival and delays in lung, colorectal, prostate and ovarian cancer: comparison between diagnostic routes

BACKGROUND: Very few studies have reported cancer outcomes of patients referred through different routes, despite the prominence of current UK cancer urgent referral guidance. AIM: This study aimed to compare outcomes of cancer patients referred through the urgent referral guidance with those who were not, with respect to stage at diagnosis, survival, and delays in diagnosis. Design of study: Analysis of hospital records. SETTING: One hospital trust in England. METHOD: The records of 889 patients diagnosed in 2000-2001 with one of four types of cancer were analysed: 409 with lung cancer; 239 with colorectal cancer; 146 with prostate cancer; and 95 with ovarian cancer. Outcome measures were diagnostic stage, survival, referral and secondary care delays. RESULTS: For lung cancer, urgent referrals had more advanced TNM (tumor, node, metastasis) stage than patients diagnosed through other routes (P = 0.035) and poorer survival (P = 0.020). There was no difference in stage or survival for the other cancers. For each cancer, a higher proportion of urgent referrals was seen within 2 weeks. Secondary care delays for lung and colorectal cancer were shorter for inter-specialty referrals. CONCLUSION: For patients with lung cancer, the guidance appears to be prioritising those in the more advanced stages of disease. This was not the case for the other three cancers. Referral delays were shorter for patients urgently referred, as is the intention of the guidance. The avoidance of delays in outpatient diagnostics probably accounts for shorter secondary care delays for inter-specialty referrals.     

RELATIONSHIP BETWEEN THE RESPONSIVENESS OF MATERNAL AND FOETAL LYMPHOCYTES TO PHYTOHAEMAGGLUTININ AND TO MICROBIAL ANTIGENS

The response of 105 maternal-foetal lymphocyte pairs to specific and non-specific stimulation were evaluated using a newly defined method of analysis. There were no significant differences in the responses of maternal or foetal lymphocytes to phytohaemogglutinin (PHA) or the various antigens as a function of concentration over the ranges tested. The maternal lymphocytes were stimulated by all of the antigens and responded to PHA three-five times more strongly than to the antigens. The foetal lymphocytes were stimulated by PHA and tetanus toxoid only and were suppressed by streptokinase-streptodornase (SKSD). They responded to stimulation by antigens at a lower level than did the maternal lymphocytes, but they responded at a much higher level to PHA. Unstimulated cultures of foetal lymphocytes incorporated more isotope than did those of maternal lymphocytes in both autologous and AB plasma. The data were cross-classified to determine whether the responses of the foetal lymphocytes varied concordantly with the responses of the maternal lymphocytes in both autologous and AB plasma by the Chi-square test for independence and by rank correlation analysis. There was no significant correlaiton in either plasma to stimulation with the antigens. Thus, the presence of antigen reactive lymphocytes in the circulation of the mother does not mean that the foetus is sensitized to that antigen. Comparison of the lymphocyte responses in autologous plasma with those in AB plasma provided evidence for the presence of circulating immunoregulatory substances. Autologous maternal plasma suppressed the lymphocyte responses to high concentrations of candida and SKSD and stimulated the response to mumps, varicella and tetanus toxoid. Autologous fetal plasma suppressed the lymphocyte responses to candida, varicell and SKSD and stimulated the response to PHA. The responsiveness of maternal lymphocytes to PHA was less in foetal plasma than in autologous maternal or AB plasma.