The beta subunit of human chorionic gonadotropin lacks specificity for malignant cells in serous effusions.

The cytologic diagnosis of malignancy is frequently straightforward. For difficult cases, multiple immunostains and immunostain panels have been investigated without consensus. beta-human chorionic gonadotropin (hCG) has been reportedly expressed in malignancies, but not in normal tissue. HCG also has been reported as a specific marker of metastases in serous fluids when detected with laboratory assays. We investigated the clinical utility of hCG in this cytologic setting. A total of 97 cases of benign and malignant effusions were studied. Each case was immunostained with monoclonal hCG using the avidin-biotin technique and diaminobenzidine as a chromogen. Additionally, a mucicarmine stain was performed on most cases. Cases were evaluated for hCG expression and mucin in a blinded fashion. After the cases were reviewed, the diagnoses were unblinded and staining patterns were evaluated. Of the 47 benign cases studied, 23 (49%) exhibited immunoreactivity to hCG in at least 5% of mesothelial cells present. In contrast, 28 of 44 (64%) adenocarcionomas exhibited a similar degree of immunostaining. In all, 21 (48%) of the adenocarcinomas were also positive for mucin; five of these mucin-positive cases were negative for hCG. The combination of mucin and hCG detected 33 of 44 (75%) adenocarcinomas. We conclude that hCG lacks the specificity for malignant cells to be of clinical use in effusion cytology.     

The future of healthcare and the pharmaceutical industry – a CEO view

In the century or so since the birth of the research-based pharmaceutical industry, there has never been a more demanding time. The most pressing issue facing virtually all big pharmaceutical companies today is research and development productivity. Despite huge investments in research and development, the number of new medicines cleared for market has declined. On the other hand, there has never been a more exciting time to do healthcare research. New sciences and technologies are opening up radically new perspectives and opportunities for the future. Medical practice is undergoing a historic shift towards more personalized medicine. Over the next 10 years we can expect significant progress in the treatment of major diseases.     

Development of specific antibody patterns and clinical symptoms following Ockelbo virus infection

Summary Sixteen patients with symptoms typical for Ockelbo disease (rash, arthralgia, fever) were enrolled in a 2 1/2 year study, during which clinical symptoms were recorded and ELISA was employed to study specific IgM, IgG and IgG subclass development. Initially, all patients presented with rash and arthralgia, and five patients still suffered from joint symptoms at the end of the study period. Ockelbo virus specific IgM was detected during the first week post onset in 6 patients and in 15 patients by day 14. One patient failed to develop specific IgM and was later diagnosed with a human parvovirus B 19 infection. All patients were IgM-negative 2 1/2 years post onset. Seroconversions or significant titer rises for specific total IgG were seen in 15 patients. IgG titers generally peaked within one year but in two patients maximum titers were seen 2 1/2 years post onset. Development of IgG1 followed that of total IgG, while IgG3, after an initial increase in all Ockelbo disease patients, remained at peak levels for one year in four patients, three of whom still had detectable IgG3 at the end of the study period. Ockelbo virus specific IgG2 or IgG4 was not detected in any of the patients.     

Amyotrophic lateral sclerosis patient antibodies label Ca2+ channel α1 subunit

Sporadic amyotrophic lateral sclerosis is an idiopathic human degenerative disease of spinal cord and brain motor neurons. Prior studies demonstrated that most patients with amyotrophic lateral sclerosis posses immunoglobulins that bind to purified L-type voltage-gated calcium channels, that titers of anti–voltage-gated calcium channel antibodies correlate with disease progression rates, and that amyotrophic lateral sclerosis patient-derived antibodies (ALS IgG) produce electrophysiological changes in the function of voltage-gated calcium channels. Using Western transfer immunoblots and enzyme-linked immunosorbent assays, the calcium ionophore–forming α₁ subunig of the voltage-gated calcium channel is now identified as the major voltage-gated calcium channel antigen to which ALS IgG binds. Additionally, the binding of an L-type voltage-gated calcium channel α₁ subunit–directed monoclonal antibody, which itself mimics the effects of ALS IgG on skeletal muscle voltage-gated calcium channel currents, is selectively prevented by preaddition of ALS IgG. Voltage-gated calcium channel–binding IgG from patients with Lambert-Eaton myasthenic syndrome appears to be differentiated from ALS IgG by the reactivity of the former to both α₁ and β subunits of the calcium channel. These assays provide further evidence linking amyotrophic lateral sclerosis to an autoimmune process, and suggest one means to differentiate immunoglobulins from patients with amyotrophic lateral sclerosis from those of patients with another autoimmune disease expressing calcium channel antibodies.