Effect of a caspase inhibitor, zVADfmk, on the inhibition of breast cancer cells by herpes simplex virus type 1.

The oncolytic effects of herpes simplex virus-1 (HSV-1) are limited, possibly because of premature death of infected cells by apoptosis, which limits the amount of progeny virus that is produced. It has been proposed that inhibition of apoptosis in infected tumor cells would allow increased viral persistence, replication and therapeutic effect. To test this hypothesis, we infected monocyte chemoattractant factor-7 (MCF-7) and MDA-MB-231 breast cancer cells with HSV-1 strain 17(+) and 17Δγ34.5 in the presence or absence of N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVADfmk), a pan-caspase inhibitor. At low doses of HSV-1 strain 17(+) and 17Δγ34.5, the growth of MCF-7 cells was reduced to 37% or 42%, respectively, of uninfected cells. However, when cells were infected in the presence of zVADfmk, cell growth was further reduced to 24 and 33%. Similar results were seen in MDA-MB-231 cells. Cells treated with zVADfmk contained roughly 10 times more infectious viral particles than cells infected without zVADfmk, as shown by both plaque-forming and quantitative polymerase chain reaction assays. To model the situation within an infected tumor, supernatant fluids were collected from infected and non-infected cell cultures and then passed to non-infected cells. In the presence of zVADfmk, the cell growth inhibitory effect became stronger with repeated passages and was attributed to viral replication, because it could be prevented by anti-HSV antibody. These results suggest that caspases represent a novel target for drugs that increase the therapeutic efficacy of oncolytic herpes viruses against breast cancer.

Raising the root. A look at orthodontic extrusion.

A simple technique using bonded wires to establish anchorage and an attachment to a tooth requires a minimum of special materials or advanced skills in orthodontics. The bonded wire stabilizes the anchor unit and avoids any adverse tooth movement.

Assimilation of polychlorinated biphenyls by a marine mollusc and comparison with a rat.

The marine mollusc Aplysia californica was fed seaweed Rhodymenia palmata contaminated with polychlorinated biphenyls (PCBs) at a high (experimental) and low (control) level for a period of 18 days in flow-through systems which limited the animals to dietary uptake. The assimilation of PCBs, determined by subtraction of fecal output from food intake, was greater at the high dosage (94 +/- 29%) than at the low dosage (84 +/- 22%). Assimilation selectivity of the different congeners favored those with lower chlorine content, and discriminated against those chlorinated in the para position on one of the rings. After assimilation, selectivity for incorporation into the hepatopancreas favored those congeners with higher chlorine contents over those with but 1 to 3 chlorines on the molecule. Similarities between incorporation into the liver of rats and into the hepatopancreas of Aplysia were found, suggesting that common mechanisms for bioaccumulation, and by extension, physiological effects, may be present in such diverse species of the animal kingdom.

The troubled employee. Absenteeism.

Absenteeism is a very costly problem in business and industry. The author discusses the dimensions of the problem, its causes and complexity, and practical steps that occupational health professionals can take to assist management in improving the problem.

The use of meditation--relaxation techniques for the management of stress in a working population.

The efficacy of meditation-relaxation techniques has been widely researched in the laboratory, but their effectiveness for management of stress in organizational settings is still relatively unexplored. The present study compared relaxation and control conditions as part of a program of stress-reduction in industry. A total of 154 New York Telephone employees self-selected for stress learned one of three techniques--clinically standardized meditation (CSM), respiratory one method meditation (ROM) or progressive relaxation (PMR)--or served as waiting list controls. At 5.5 months, the treatment groups showed clinical improvement in self-reported symptoms of stress, but only the meditation groups (not the PMR group) showed significantly more symptom reduction than the controls. The meditation groups had a 78% compliance rate at 5.5 months with treatment effect seen whether subjects practiced their techniques frequently or occasionally. The safe and inexpensive semi-automated meditation training has considerable value for stress-management programs in organizational settings.

Choroidal melanoma and retinal tear.

The patient's eye contained a choroidal melanoma and a horseshoe retinal tear. Clinical recognition of the tumor led to the correct diagnosis and enucleation, avoiding unnecessary and potentially detrimental retinal detachment operations.

The Bronx study -- a trial of health care management.

We have reviewed our experiences in the Bronx study, which was a one-year pilot study by the New York Telephone Medical Department, aimed at expanding our involvement in the health care of company employees without duplicating what already existed in the community. We learned much from the study, chiefly in its evolution of a concept which we call Health Care Management (HCM). The three basic elements of HCM are (1) to deliver just enough care in-house to gain from the employee his authority to let us manage his health, (2) to document all of his health data confidentially, and (3) to work closely with community care resources in treating those clinical episodes needing their services. We learned that the two key ingredients of such a program are an adequate, comprehensive record system and thorough training of every member of our in-house HCM team. We are intensively developing both of these in preparation for incorporating HCM into our medical program throughout the New York company.