The Hantaan virus glycoprotein precursor is cleaved at the conserved pentapeptide WAASA.

The medium segment of the tripartite negative-stranded RNA genome of hantaviruses encodes for the predicted glycoprotein precursor GPC. We have demonstrated here the expression of the glycoprotein precursor of Hantaan virus following transfection of mammalian cells. The cleavage of the precursor into the glycoproteins G1 and G2 followed the rules for signal peptides and seemed to occur directly at the pentapeptide motif "WAASA." Our data indicate that the signal peptidase complex is responsible for the proteolytic processing of the precursor GPC of Hantaan virus. The comparison of this region of the glycoprotein precursor, including the absolutely conserved WAASA motif, suggests a similar cleavage event for all hantavirus glycoproteins.

Efficient replication of adenovirus despite the overexpression of active and nondegradable p53.

The adenoviral oncoproteins E1B-55 kDa and E4orf6 inactivate and destabilize the tumor suppressor protein p53, thereby contributing to malignant transformation. However, it is unclear whether the elimination of p53 also contributes to the efficiency of viral replication. Furthermore, it is controversial whether adenoviruses with a deletion in the E1B-55 kDa-coding region might selectively replicate in cells with a mutation or deletion of the p53 gene and, therefore, represent a tool in cancer therapy. To address the role of p53 in virus replication, amino acid substitutions were introduced into the NH(2)-terminal portion of p53, replacing residues 24-28 with the corresponding sequence of the human p53-homologue p73. This replacement leaves p53 transcriptionally active but renders the modified protein, termed p53mt24-28, completely resistant to inhibition and degradation by adenoviral oncoproteins. Surprisingly, even strong overexpression of p53 or p53mt24-28 allowed the virus to replicate as efficiently as in the absence of p53 proteins, both in tumor cells and in primary endothelial cells. Also, p53 or p53mt24-28 did not reduce the amount of virus released from infected cells. These observations were made in primary cells or in cell lines that were capable of expressing the p53-agonist p14ARF. Thus, active p53 does not inhibit the growth of adenovirus. Alternative strategies should be used to improve the utility of adenoviruses in cancer therapy.

Calcium-channel antagonists and nitrates in coronary artery bypass patients receiving radial artery grafts.

OBJECTIVE: To review the literature assessing the role of vasodilators for the prevention of vasospasm leading to graft failure in patients receiving the radial artery (RA) as a conduit in coronary artery bypass grafting (CABG). DATA SOURCE: A MEDLINE search (January 1966-May 2000) was performed using calcium-channel antagonists, nitrates, radial artery, and coronary artery bypass as key words. English-language articles were identified, and the references of these articles were used to further identify pertinent articles. DATA SYNTHESIS: RAs can be used as conduits in CABG. It has been suggested that failure of these grafts may be due to vasospasm, leading to occlusion observed angiographically. Calcium-channel antagonists and nitrates have been proposed as a means of preventing vasospasm and subsequent graft failure. CONCLUSIONS: Currently published data on the use of calcium-channel antagonist or nitrate therapy as prophylaxis against vasospasm in patients receiving RA grafts are inconclusive. Systematic evaluations of currently available pharmacologic agents are needed to guide clinical practice in this area.

Transcranial Doppler ultrasonography as a screening technique for detection of a patent foramen ovale before surgery in the sitting position.

BACKGROUND: Venous air embolism has been reported to occur in 23-45% of patients undergoing neurosurgical procedures in the sitting position. If venous air embolism occurs, a patent foramen ovale (PFO) is a risk factor for paradoxical air embolism and its sequelae. Preoperative screening for a PFO is therefore recommended by some investigators. The reference standard for identifying a PFO is contrast-enhanced transesophageal echocardiography (c-TEE). Contrast-enhanced transcranial Doppler ultrasonography (c-TCD) and contrast-enhanced transthoracic echocardiography (c-TTE) are noninvasive alternative methods, but so far there are no studies as to their diagnostic validity in neurosurgical patients. METHODS: The sensitivity and specificity of c-TCD and c-TTE in detecting a PFO were determined in a prospective study using c-TEE as the reference standard. Preoperative c-TCD, c-TTE, and c-TEE studies were performed during the Valsalva maneuver after intravenous echo-contrast medium (D-Galactose, Echovist-300, Schering AG, Berlin, Germany) was administered in 92 consecutive candidates (47 men and 45 women; mean age, 51 yr; range, 25-72 yr) before neurosurgical procedures in the sitting position. RESULTS: A PFO was detected in 24 of the 92 patients (26.0%) using c-TEE. c-TCD correctly identified 22 patients, whereas c-TTE only correctly identified 10. This corresponds to a sensitivity of 0.92 for c-TCD and 0.42 for c-TTE. The negative predictive value was 0.97 for c-TCD compared with 0.83 for c-TTE. The prevalence of a PFO in patients with a posterior fossa lesion was 27%, and in the group with cervical disc herniation was 24% as detected by c-TEE. The incidence of intraoperative venous air embolism was 35% in cases of cervical foraminotomy and 75% in posterior fossa surgery as detected by c-TEE. CONCLUSIONS: c-TCD is a highly sensitive and highly specific method for detecting a PFO. Because c-TCD is noninvasive, it may be more suitable than c-TEE for routine preoperative screening for a PFO. C-TTE is not reliable in detecting a PFO.

Actinic keratosis is squamous cell carcinoma.

BACKGROUND: The prevalence of nonmelanoma skin cancer in the United States is alarming. It can be most appropriately treated if the earliest manifestation of cutaneous squamous cell carcinoma is recognized. METHODS: Clinical, histologic, and molecular biology, considerations were reviewed to determine whether actinic keratosis is the earliest clinical manifestation of cutaneous squamous cell carcinoma. RESULTS: The clinical, histologic, and molecular parameters of actinic keratosis are those of squamous cell carcinoma. CONCLUSION: Actinic keratosis does not transform, convert, or progress into cutaneous squamous cell carcinoma but is the earliest clinically recognizable manifestation of this malignancy.

Organizing state dermatologic societies.

Each year state legislatures, boards of medicine, departments of insurance, and other authorities promulgate laws and rules that affect the daily practice of dermatology. It is critical that dermatologists in each state form and maintain a strong state dermatologic society. Specific suggestions for forming and strengthening such societies are described and available resources are reviewed.

Dermatology. Positioned for health care reform.

Dermatologic services will of necessity be a fundamental part of any quality, cost-conscious health care system because (1) we treat medically necessary and economically significant diseases, (2) our area of expertise includes a distinct body of medical knowledge over which no other health professional has comparable expertise, and (3) our services are provided in a cost-effective manner.

Microcystic adnexal carcinoma (sclerosing sweat duct carcinoma).

Microcystic adnexal carcinoma is a relatively uncommon tumor first described in 1982. Most commonly presenting as a facial plaque or nodule, this highly invasive tumor is characterized by slow growth and relentless local destruction. We report the presence of microcystic adnexal carcinoma in the neck, a previously unreported site. The patient was a 48-year-old man who had received radiation therapy at age 5 to shrink the thymus gland and subsequent radiation therapy after excision of a thyroid tumor at age 35. The results of immunohistochemical stains were consistent with the hypothesis that this tumor develops from pluripotential cells capable of follicular and eccrine differentiation.

Universal health coverage.

Although over 12% of our gross national product is spent on health care, approximately 14% to 17% of Americans are not covered by any form of health insurance. The cost, benefits, and deficiencies of private insurance and government programs are discussed in this article. The increasing percentage of persons surviving into older age, improved technology, patient demands and expectations, administrative costs, medical malpractice and defensive medicine, and other factors contribute to the steadily increasing cost of care. Physicians must participate in health care reform or passively accept determinations made in their absence.

Physician advertising.

Practically nonexistent until the late 1970s, advertising by physicians has become commonplace. Although informational and educational advertising may contain information that potential patients may find to be useful, laudatory and predatory advertising are unethical and may be patently illegal. There is a conflict between the obligations of a physician to his patients and the intentions of advertising. The role of the Federal Trade Commission and state regulations are discussed.

Ethics in pharmaceutical advertising.

Pharmaceutical manufacturing is one of the most financially lucrative industries in America due, in part, to massive marketing and advertising. The content of many symposia and medical journals as well as physician prescribing decisions seems to be influenced by the promotional efforts of pharmaceutical companies. In an effort to increase sales, the industry now advertises directly to the public. The role of the Food and Drug Administration and ethical standards established by medical organizations are discussed.