Treatment of recurrent and persistent germ cell tumors with cisplatin, vinblastine, and bleomycin

Four patients were treated with vinblastine, cisplatin, and bleomycin for recurrent or persistent germ cell tumors. In all patients a clinical response was achieved. In 2 patients complete response was attained and they are free of disease following second-look laparotomy. One had a mixed germ cell tumor that persisted as dysgerminoma following primary chemotherapy. The other was a true hermaphrodite with pure dysgerminoma. In patients with endodermal sinus tumor transient response was achieved, but the tumors recurred and the patients died within 6 months.     

Polarity of heteroduplex formation promoted by Escherichia coli recA protein.

When recA protein pairs circular single strands with linear duplex DNA, the circular strand displaces its homolog from only one end of the duplex molecule and rapidly creates heteroduplex joints that are thousands of base pairs long [DasGupta, C., Shibata, T., Cunningham, R. P. & Radding, C. M. (1980) Cell 22, 437-446]. To examine this apparently polar reaction, we prepared chimeric duplex fragments of DNA that had M13 nucleotide sequences at one end and G4 sequences at the other. Circular single strands homologous to M13 DNA paired with a chimeric fragment when M13 sequences were located at the 3' end of the complementary strand but did not pair when the M13 sequences were located at the 5' end. Likewise circular single-stranded G4 DNA paired with chimeric fragments only when G4 sequences were located at the 3' end of the complementary strand. To confirm these observations, we prepared fd DNA labeled only at the 5' or 3' end of the plus strand, and we examined the susceptibility of these labeled ends to digestion by exonucleases when joint molecules were formed. Eighty percent of the 5' label in joint molecules became sensitive to exonuclease VII. Displacement of that 5' end by recA protein was concerted because it did not occur in the absence of single-stranded DNA or in the presence of heterologous single strands. By contrast, only a small fraction of the 3' label became sensitive to exonuclease VII or exonuclease I. These observations show that recA protein forms heteroduplex joints in a concerted and polarized way.     

Channels formed by botulinum, tetanus, and diphtheria toxins in planar lipid bilayers: relevance to translocation of proteins across membranes.

The heavy chains of both botulinum neurotoxin type B and tetanus toxin form channels in planar bilayer membranes. These channels have pH-dependent and voltage-dependent properties that are remarkably similar to those previously described for diphtheria toxin. Selectivity experiments with anions and cations show that the channels formed by the heavy chains of all three toxins are large; thus, these channels could serve as "tunnel proteins" for translocation of active peptide fragments. These findings support the hypothesis that the active fragments of botulinum neurotoxin and tetanus toxin, like that of diphtheria toxin, are translocated across the membranes of acidic vesicles.     

Real-world analysis of patients with haemophilia A and haemophilia A carriers in the United States: Demographics,clinical characteristics and costs

Introduction

Females with haemophilia A (HA [FHAs]) and HA carriers (HACs) have an increased risk of bleeding and complications compared to the general population.

Aim

To examine the characteristics, billed annualised bleed rates (ABR_b), costs and healthcare resource utilisation for males with HA (MHAs), FHAs and HACs in the United States.

Methods

Data were extracted from the IBM® MarketScan® Research Databases (Commercial and Medicaid) for claims during the index period (July 2016 to September 2018) and analysed across MHAs, FHAs and HACs.

Results

Dual diagnosis females (DDFs; both HA and HAC claims) were grouped as a separate cohort. MHAs were generally younger than females (all cohorts) by up to 19 years (Commercial) and 23 years (Medicaid). ABR_b >0 was more frequent in females. Factor VIII claims were higher for MHAs versus female cohorts. Joint-related health issues were reported for 24.4 and 25.6% (Commercial) and 29.3 and 26.6% (Medicaid) of MHAs and FHAs, respectively; lower rates were reported in the other two cohorts. Heavy menstrual bleeding claims occurred for approximately a fifth (Commercial) to a quarter (Medicaid) of female cohorts. All-cause emergency department and inpatient visits in FHAs and DDFs were similar to, or more frequent than, those in MHAs; bleed-related inpatient visits were infrequent. In MHAs (Commercial), mean all-cause total costs ($214,083) were higher than in FHAs ($40,388), HACs ($15,647) and DDFs ($28,320) with similar trends for Medicaid patients.

Conclusions

FHAs and HACs may be undermanaged and undertreated. Further research is needed to fully understand these cohorts' bleeding rates, long-term complications and costs.     

Adaptive Bayesian variable clustering via structural learning of breast cancer data

The clustering of proteins is of interest in cancer cell biology. This article proposes a hierarchical Bayesian model for protein (variable) clustering hinging on correlation structure. Starting from a multivariate normal likelihood, we enforce the clustering through prior modeling using angle-based unconstrained reparameterization of correlations and assume a truncated Poisson distribution (to penalize a large number of clusters) as prior on the number of clusters. The posterior distributions of the parameters are not in explicit form and we use a reversible jump Markov chain Monte Carlo based technique is used to simulate the parameters from the posteriors. The end products of the proposed method are estimated cluster configuration of the proteins (variables) along with the number of clusters. The Bayesian method is flexible enough to cluster the proteins as well as estimate the number of clusters. The performance of the proposed method has been substantiated with extensive simulation studies and one protein expression data with a hereditary disposition in breast cancer where the proteins are coming from different pathways.