Individual cell-by-cell quantitation of lymphocyte surface membrane Ig in normal and CLL lymphocyte and during ontogeny of mouse B lymphocytes by immunoperoxidase assay

A new quantitative immunoperoxidase method is presented for determining absolute amounts of peroxidase and, consequently, surface antigen densities of individual cells in B lymphocytes from normal individuals, from subjects with CLL and prolymphocytic leukemia, and during ontogeny of B lympocytes in the mouse. The following results were observed: (1) The density of B antigenic sites were lower on CLL than on normal B lymphocytes. (2) The B antigens density of leukemic lymphocytes varied less from cell to cell, forming a homogeneous peak on histograms. (3) In a very rare case of CLL, the antigen density was measured at the time of initial diagnosis (22,500 sites or 647 U) and during the development of a blastic crisis (135,000 sites or 2576 U). The cell by cell distribution changed from a homogeneous peak with a low number of antigenic sites per cell to a heterogeneous peak with a high number of antigenic sites per cell. (4) In prolymphocytic leukemia, the density of B antigenic sites was greater than on normal B lymphocytes and much more heterogeneous than on CLL lymphocytes. (5) During ontogeny of B lymphocytes in the mouse, maturation is associated with the appearance of a population of cells of intermediate to high Smig density. The finding of a decrease in, and altered distribution of, surface markers in CLL is compared with these ontologic findings in the mouse, and the concept that a monoclonal B lymphocyte in CLL may be arrested at a particular stage in its differentiation is discussed.     

When Genetic Load Does Not Correlate with Phenotypic Spectrum: Lessons from the GnRH Receptor (GNRHR)

Context: A broad spectrum of GnRH-deficient phenotypes has been identified in individuals with both mono- and biallelic GNRHR mutations. Objective: The objective of the study was to determine the correlation between the severity of the reproductive phenotype(s) and the number and functional severity of rare sequence variants in GNRHR. Subjects: Eight hundred sixty-three probands with different forms of GnRH deficiency, 46 family members and 422 controls were screened for GNRHR mutations. The 70 subjects (32 patients and 38 family members) harboring mutations were divided into four groups (G1-G4) based on the functional severity of the mutations (complete or partial loss of function) and the number of affected alleles (monoallelic or biallelic) with mutations, and these classes were mapped on their clinical phenotypes. Results: The prevalence of heterozygous rare sequence variants in GNRHR was significantly higher in probands vs. controls (P < 0.01). Among the G1-G3 groups (homozygous subjects with successively decreasing severity and number of mutations), the hypogonadotropic phenotype related to their genetic load. In contrast, subjects in G4, with only monoallelic mutations, demonstrated a greater diversity of clinical phenotypes. Conclusions: In patients with GnRH deficiency and biallelic mutations in GNRHR, genetic burden defined by severity and dose is associated with clinical phenotype. In contrast, for patients with monoallelic GNRHR mutations this correlation does not hold. Taken together, these data indicate that as-yet-unidentified genetic and/or environmental factors may combine with singly mutated GNRHR alleles to produce reproductive phenotypes.     

New cancer cases in France in 2015 attributable to infectious agents: a systematic review and meta-analysis

To provide an assessment of the burden of cancer in France in 2015 attributable to infectious agents. A systematic literature review in French representative cancer cases series was undertaken of the prevalence of infectious agents with the major associated cancer types. PubMed was searched for original studies published up to September 2016; random-effects meta-analyses were performed. Cancer incidence data were obtained from the French Cancer Registries Network, thereby allowing the calculation of national incidence estimates. The number of new cancer cases attributable to infectious agents was calculated using population-attributable fractions according to published methods. Of the 352,000 new cancer cases in France in 2015, 14,336 (4.1% of all new cancer cases) were attributable to infectious agents. The largest contributors were human papillomavirus (HPV) and Helicobacter pylori, responsible for 6333 and 4406 new cancer cases (1.8 and 1.3% of all new cancer cases) respectively. Infectious agents caused a non-negligible number of new cancer cases in France in 2015. Most of these cancers were preventable. The expansion of vaccination (i.e., for hepatitis B virus and HPV) and screen-and-treat programs (for HPV and hepatitis C virus, and possibly for H. pylori) could greatly reduce this cancer burden.     

Platelet-melanoma cell interaction is mediated by the glycoprotein IIb- IIIa complex

A human malignant melanoma cell line (M3Dau) was observed by electron microscopy to interact directly with human platelets and induced platelet aggregation. Fab fragments of a monoclonal antibody MoAb (LYP18), directed against the platelet glycoprotein (GP) IIb-IIIa complex, inhibited platelet-melanoma interactions and platelet-platelet aggregation. M3Dau melanoma cells bind LYP 18 and synthesize IIb-IIIa- like GPs. When the melanoma cells were preincubated with LYP 18, tumor- platelet interaction did not occur, suggesting that the interaction may be mediated by the IIb-IIIa-like GPs present on the melanoma cell surface. Glanzmann's thrombasthenic platelets, lacking GPIIb and IIIa, did not interact with melanoma cells, indicating that the platelet GPIIb-IIIa complex is also necessary for the platelet-melanoma cell interaction. This work demonstrates the importance of the IIb-IIIa-like GPs, present on M3Dau melanoma cells, in mediating tumor-platelet interactions.     

Control of hypertension with medication: a comparative analysis of national surveys in 20 countries

Objective

To examine hypertension management across countries and over time using consistent and comparable methods.

Methods

A systematic search identified nationally representative health examination surveys from 20 countries containing data from 1980 to 2011 on blood pressure measurements, the diagnosis and treatment of hypertension and its control with antihypertensive drugs. For each country, the prevalence of hypertension (i.e. systolic blood pressure ≥ 140 mmHg or antihypertensive use) and the proportion of hypertensive individuals whose condition was diagnosed, treated or controlled with medications (i.e. systolic pressure < 140 mmHg) were estimated.

Findings

The age-standardized prevalence of hypertension varied between countries: for individuals aged 35 to 49 years, it ranged from around 12% in Bangladesh, Egypt and Thailand to around 30% in Armenia, Lesotho and Ukraine; for those aged 35 to 84 years, it ranged from 20% in Bangladesh to more than 40% in Germany, the Russian Federation and Turkey. The age-standardized percentage of hypertensive individuals whose condition was diagnosed, treated or controlled was highest in the United States of America: for those aged 35 to 49 years, it was 84%, 77% and 56%, respectively. Percentages were especially low in Albania, Armenia, the Islamic Republic of Iran and Turkey. Although recent trends in prevalence differed in England, Japan and the United States, treatment coverage and hypertension control improved over time, particularly in England.

Conclusion

Globally the proportion of hypertensive individuals whose condition is treated or controlled with medication remains low. Greater efforts are needed to improve hypertension control, which would reduce the burden of noncommunicable diseases.