The Functional Deficiency of B Lymphocytes in Patients with Lung Cancer is Due to Inadequate T-Cell Help and Excessive Suppression by T and Non-T Cells

The proliferative and plaque-forming cell (PFC) responses of unseparated mononuclear cells (MNC) and B- and T-cell-enriched populations of cells were analyzed in 15 patients with lung cancer to determine the mechanisms involved in the functional abnormality of their B cells. The PFC responses of the MNC of the patient group were significantly lower than those of normal controls. In addition, the enriched B cells of several patients showed a further decrease in their PFC responses after coculture with autologous Tcells compared with their respective MNC responses. The proliferative response against phytohemagglutinin (PHA) was also lower in many of the patients after similar cocultures. Cocultures of patients' B cells with T cells from normal controls significantly enhanced the PFC responses in 7 patients. In most of the normal controls, B lymphocytes showed a significant decrease in their PFC responses after coculture with the patients' T cells. Although the percentages of total T cells, T-helper, and B cells were within the normal range, the number of suppressor T cells was significantly higher in the patient group. These results indicate that a combination of insufficient T-cell help, excessive suppression by both T and non-T cells, and a possible intrinsic B-cell abnormality are responsible for the B-cell functional deficiency observed in patients with lung cancer.     

Invasive Haemophilus influenzae type b disease in the Oxford region (1985-91)

For a seven year period (1985-91) clinical and epidemiological data were prospectively collected on children aged < 10 years with microbiologically confirmed invasive Haemophilus influenzae type b infection in the Oxford region to study the epidemiology of the disease and determine the potential impact of early primary immunisation in infants. Computer records of primary immunisations given to these cases were retrospectively analysed and, where necessary, hospital and general practitioner records were searched to determine the immunisation history. Over the seven year period, 416 cases of invasive H influenzae type b disease were reported. Widescale immunisation against H influenzae type b began in 1991 as part of a regional trial. The estimated annual incidence for invasive disease between 1985 and 1990 was 35.5 cases per 100,000 children aged less than 5 years; for H influenzae type b meningitis it was 25.1 per 100,000 children aged less than 5 years. The cumulative risks for invasive disease and meningitis by the fifth birthday were one in 560 and one in 800 respectively. The majority of disease (71%) occurred in children less than 2 years of age with the peak monthly incidences at 6 and 7 months of age. The overall mortality was 4.3% and 50% of these deaths occurred suddenly. Most (91%) of the children had received at least one primary immunisation against diphtheria, tetanus, and pertussis before H influenzae type b infection and there was only one case of parental refusal of immunisation. None had received H influenzae type b immunisation. Given a vaccine uptake of 90% by 5 months of age it is estimated that at least 82% of the H influenzae type b infections could have been prevented. Extrapolated nationally, 1150 cases of infection and 50 deaths could be prevented each year by routine primary immunisation.     

False-negative results by polymerase chain reaction due to contamination by glove powder

The polymerase chain reaction (PCR) technique has become an important, widely employed method for the detection and quantitation of the nucleic acid sequences used in the diagnosis and monitoring of genetic and infectious diseases. Much attention has been directed at the problem of false-positive PCR results, which are generally attributed to low-level laboratory contamination of amplified sequences ("carryover"). In contrast, few investigators have commented on the somewhat less frequent, but equally problematic, false-negative PCR results. Investigation of the source of sporadic false-negative PCR reactions found that glove powder, inadvertently introduced into tubes when gloves are changed in an effort to reduce false-positive results, can nonspecifically inhibit each of the major steps in the PCR detection process. Methodologic precautions are recommended to minimize this problem.     

A patenting perspective on human neutrophil elastase (HNE) inhibitors (2014-2018) and their therapeutic applications

Introduction: Human neutrophil elastase (HNE) is involved in a variety of serious chronic diseases, especially cardiopulmonary pathologies. For this reason, the regulation of HNE activity represents a promising therapeutic approach, which is evident by the development of a number of new and selective HNE inhibitors, both in the academic and pharmaceutical environments.

Areas covered: The present review analyzes and summarizes the patent literature regarding human neutrophil elastase inhibitors for the treatment of cardiopulmonary diseases over 2014–2018.

Expert opinion: HNE is an interesting and defined target to treat various inflammatory diseases, including a number of cardiopulmonary pathologies. The research in this field is quite active, and a number of HNE inhibitors are currently in various stages of clinical development. In addition, new opportunities for HNE inhibitor development stem from recent studies demonstrating the involvement of HNE in many other inflammatory pathologies, including rheumatoid arthritis, inflammatory bowel disease, skin diseases, and cancer. Furthermore, the development of dual HNE/proteinase 3 inhibitors is being pursued as an innovative approach for the treatment of neutrophilic inflammatory diseases. Thus, these new developments will likely stimulate new and increased interest in this important therapeutic target and for the development of novel and selective HNE inhibitors.