Diffuse malignant mesothelioma of the peritoneum and pleura, analysis of markers.

Diffuse malignant mesothelioma of the peritoneum is a rare diagnosis. Despite many histopathologic similarities between peritoneal and pleural tumors, clinical and prognostic features may be quite different. There is a paucity of data evaluating molecular features of peritoneal mesotheliomas. Therefore, we compared the results of a battery of immunohistochemical markers, some with therapeutic implications, in patients with primary peritoneal or pleural mesotheliomas. We examined 24 peritoneal and nine pleural malignant mesotheliomas with a battery of immunohistochemical markers (cytokeratin AE1/3, calretinin, c-kit/CD117, desmin, epidermal growth factor receptor (EGFR), estrogen receptors (ER), progesterone receptors (PR), MIB-1, and cleaved caspase-3) in an attempt to distinguish any differences in this tumor arising in these two distinct locations. The results indicate that the only marker to show a significant difference in its staining pattern between these two sites was EGFR (P=0.0004). In all, 92% (22/24) of peritoneal tumors demonstrated 3+ or 4+ immunoreactivity with EGFR, opposed to only 33% (3/9) pleural tumors. There was no significant difference in immunoreactivity between the pleural and peritoneal tumors with c-kit, ER, PR, cleaved caspase 3, calretinin, and desmin. There was a trend toward increased cytokeratin (P=0.07) and MIB-1 (P=0.08) expression in the peritoneal group. There was no significant difference in age, sex, or histologic subtype between the two locations. In conclusion, despite similarities between peritoneal and pleural mesothelioma, there are differences between this neoplasm arising in these two sites. The EGFR expression is more pronounced in peritoneal tumors compared to pleural tumors. The increased expression of EGFR in the peritoneal lesions may be of clinical significance with the recent emergence of epidermal growth factor receptor-targeted therapies.     

Blood and Marrow Transplant Clinical Trials Network State of the Science Symposium 2007.

Outcomes of hematopoietic cell transplantation are steadily improving. New techniques have reduced transplant toxicities, and there are new sources of hematopoietic stem cells from unrelated donors. In June 2007 the Blood and Marrow Transplant Clinical Trials Network convened a State of the Science Symposium of more than 200 participants in Ann Arbor to identify the most compelling clinical research opportunities in the field. This report summarizes the symposium's discussions and identifies eleven high priority clinical trials that the network plans to pursue over the course of the next several years.     

Characteristics of a persistent respiratory syncytial virus infection in HeLa cells

Persistent infection with respiratory syncytial (RS) virus has been established in HeLa cells. The persistently infected cell line (HeLa_RS) continues to produce virus (RSpi) at low levels after 230 passages during 3 years. The cells are morphologically similar to the parental HeLa cell line, and susceptible to vesicular stomatitis virus, but resist superinfection with standard RS virus (RS_wt). The block in RS_wt replication is not at attachment. Although infectious center and immunofluorescence assays suggested that only 5 to 30% of the cells in the culture were infected, 30 of 32 clones isolated from HeLa_RS contained some cells with virus antigen and 23 of those clones produced virus. All the clones, including the 2 that appeared not to be infected, were more resistant to RS_wt than HeLa. The clones that produced virus were significantly more resistant than the others. RS_pi is a small-plaque mutant, but not a temperature-sensitive mutant, of RS_wt. Although prior infection of HeLa with RS_pi interferes with RS_wt replication, the interference appears not to be caused by defective interfering particles, but by RS_pi virions. RS_pi initiates a persistent infection in HeLa only after a cytolytic phase similar to that which preceded the establishment of HeLa_RS.     

Viral load,CD4 percentage,and delayed-type hypersensitivity in subjects receiving the HIY-1 Immunogen and antiviral drug therapy

Two trials of subjects inoculated with the inactivated, gp120-depleted HIV-1 Immunogen are reported. In one study, in which 19 subjects received ZDV and 8 subjects received ddI, treatment with the HIV-1 Immunogen did not affect the pharmacokinetic parameters of the antiviral drugs. In another study, 65 subjects who were previously immunized with the HIV-1 Immunogen over a mean period of 4.0 years (range, 1.2–5.4 years) received inoculations at 0 and 6 months. At some point during this 48-week study, 72% of the subjects (47/65) were receiving antiviral drug therapy. The HIV-1 DNA load in CD4 cells and CD4 percentage were found to be stable over the 48-week period. Delayed-type hypersensitivity to HIV-1 antigens increased after two inoculations with the HIV-1 Immunogen. In these two trials, no serious treatment-related adverse events were documented in the subjects. The two studies presented herein are the first to suggest that an immune-based therapy such as the HIV-1 Immunogen can be combined safely with antiviral drugs, supporting further study to evaluate the clinical utility of this approach.     

Borrelia burgdorferi in ticks (Acari: Ixodidae) from coastal Virginia

Ixodid ticks removed from hosts and from vegetation during March-November 1987 at sites in coastal Virginia and North Carolina were examined for Borrelia burgdorferi. B. burgdorferi was evident in nine (22%) Ixodes cookei Packard removed from rice rats (Oryzomys palustris), a white-footed mouse (Peromyscus leucopus), and raccoons (Procyon lotor); four (6%) Amblyomma americanum (L.) removed from raccoons; and two (3%) Dermacentor variabilis (Say) removed from a raccoon and a rice rat. B. burgdorferi was also detected in Ixodes dentatus Marx removed from a brown thrasher (Toxostoma rufum), a Carolina wren (Thryothoros ludovicianus), and a towhee (Piplio erythrophthalamus); and in Haemaphysalis leporispalustris (Packard) removed from a brown thrasher and a white-throated sparrow (Zonotrichia albicollis) netted at Kiptopeke Beach, Va. Two Ixodes dammini Spielman, Clifford, Piesman & Corwin were collected on Parramore Island; one specimen was examined for spirochetes, and it was infected with B. burgdorferi. No spirochetes were detected in host-seeking A. americanum and Amblyomma maculatum Koch removed from vegetation. The plasma of one P. leucopus and sera obtained from two P. lotor contained antibodies to B. burgdorferi. All infected ticks and the seroreactive hosts were collected from the Eastern Shore of Virginia.     

The fidelity of phosphorylation of the adenovirus DNA-binding protein by an in vitro nuclear protein kinase from virus-infected cells.

The type 5 adenovirus single-strand-specific DNA-binding protein is phosphorylated and can be labeled by the addition of ³²PO₄ to the medium of infected cells. An infected cell nuclear protein kinase activity is capable of phosphorylatiog the single-strand-specific DNA-binding protein in vitro (A. D. Levinson, E. H. Postel, and A. J. Levine. The fidelity of phosphorylation by this in vitro protein kinase activity was tested by comparing the ³²P-labeled partial peptides generated by Staphylococcus aureus protease digestion of the ³²P-labeled DNA-binding protein which had been phosphorylated in vivo or in vitro. Identical ³²P-labeled partial peptides were obtained from the DNA-binding protein whether it was phosphorylated in vivo or in vitro. A second nuclear protein of 36,000 MW was also faithfully phosphorylated by the in vitro nuclear protein kinase activity.     

Dendritic reorganization of abdominal motoneurons during metamorphosis of the moth, Manduca sexta

During metamorphosis in the hawkmoth Manduca sexta, muscles of the abdominal body wall undergo a reorganization. Many die at the end of larval life and are replaced in the adult by newly generated muscles. We have identified several of the motoneurons innervating these muscles and followed them through metamorphosis. The morphology of larval motoneurons is correlated with their target location. Those with medial targets have bilateral dendritic fields, whereas those with lateral targets have dendrites restricted to one side of the segmental ganglion. Some motoneurons innervate the same muscle in all stages of life, but the majority lose their larval targets following entry into the pupal stage. Although some of the latter group also die at this time, most survive to innervate a new adult target. These "respecified" motoneurons undergo a period of dramatic dendritic growth during metamorphosis. The results demonstrate that these identified neurons are capable, under the appropriate conditions of existing in more than one stable morphology.     

"Crack" cocaine-associated stroke

We present three cases of "crack" cocaine-associated stroke, together with a review of cocaine-associated cerebrovascular complications. Unlike previously reported cases tentatively associating ischemic stroke with cocaine, our patients had no other potential causes for their strokes. Although the exact mechanism of cocaine-related stroke remains uncertain, both disordered neurogenic control of the cerebral circulation as well as systemic factors (ie, acute hypertension) may play a role.     

Characterization and cross-reactivity of rabbit antisera to plaque toxins

The effects of heat labile, high molecular weight water-soluble toxins from bacterial plaque on HL60 promyelocytic cells were examined. On gel filtration, four inhibitors of HL60 cell growth and two inhibitors of HeLa cell growth (PT1, PT2) were detected. The first and third HL60 cell inhibitors corresponded to the two HeLa cell inhibitors. The last eluted HL60 cell inhibitor (plaque leukotoxin, PL) did not inhibit HeLa cell growth. Anti-PT2 antibodies reduced the activity of enriched PT2 by 20-50%, but all other antisera tested exhibited no effect. Anti-PL antibodies detected antigens from Actinobacillus actinomycetemcomitans, although anti-A. actinomycetemcomitans and anti-Capnocytophaga sputigena antibodies did not react with plaque extract. These findings suggest that the plaque toxins examined in this study were probably not derived from these two bacteria.