p53 nuclear protein expression is an independent prognostic marker in clinically localized prostate cancer patients undergoing radical prostatectomy

Immunohistochemical (IHC) staining for p53 protein nuclear expression was evaluated in archival paraffin-embedded radical prostatectomy specimens from 139 patients with clinically localized prostate cancer followed up from 1 to 8 (mean, 4) years. Elevated nuclear p53 protein expression was detected in 85 (61%) of 139 patients, being heterogeneous and focal in the majority of specimens. Only four specimens displayed homogeneous nuclear accumulation of p53 protein. Disease progression, most commonly prostate-specific antigen elevation, was noted in 46 (33%) patients, with 39 (85%) having positive p53 protein IHC stains. Conversely, 93 (67%) of 139 have not recurred, with 46 (49%) having positive p53. Of all 54 p53-negative patients, 47 (87%) have had no disease recurrence. An increased p53 protein IHC stain was associated with a higher pathological stage (T1 and T2, 51% versus >/=T3, 69%) and Gleason score 2-4, 17%; 5-7, 72%; and 8-10, 87.5%). Despite these associations, p53 IHC staining was an independent predictor of disease-free survival in a multivariate analysis of p53, age, race, stage, and grade. This study revealed that a majority of clinically localized prostate cancers heterogeneously express elevated nuclear levels of p53 protein in at least a subset of malignant cells, and that this expression is an independent predictor of disease progression in prostate cancer patients after radical prostatectomy.     

Restriction endonuclease mapping and molecular cloning of the human herpesvirus 6 variant B strain Z29 genome

Human herpesvirus 6(HHV-6) variants A and B differ in cell tropism, reactivity with monoclonal antibodies, restriction endonuclease profiles, and epidemiology. Nonetheless, comparative nucleotide and amino acid sequences from several genes indicate that the viruses are very highly conserved genetically, The B variant is the major etiologic agent of exanthem subitum and is frequently isolated from children with febrile illness; no disease has been etiologically associated with HHV-6A. One HHV-6A strain has been cloned and sequenced, but similar information and reagents are not available for HHV-6B. We report here the determination of maps of the restriction endonuclease cleavage sites for BamHI, C1aI, HindIII, KpnI, and Sa1I, and the cloning in plasmids and bacteriophages of fragments representing over 95% of the HHV-6B strain Z29 [HHV-6B(Z29)] genome. Hybridization experiments and orientation of several blocks of nucleotide sequence information onto the genomic map indicate that HHV-6A and HHV-6B genomes are colinear.     

Gastrointestinal autonomic nerve tumor: further observations regarding an ultrastructural and immunohistochemical analysis of six cases

Gastrointestinal autonomic nerve tumor (GANT) is a specialized form of stromal neoplasm whose ultrastructural features support a myenteric plexus derivation and provide the basis for its diagnosis. GANT actual frequency, relationship to skeinoid fibers, and CD34 expression status are some of the controversial aspects of this entity. Out of 14 gastrointestinal stromal tumors gathered during a 1-year period, six (42%) instances were diagnosed as GANT by electron microscopic study of at least five ultrathin sections per case. Additionally, GANTs were immunohistochemically investigated with a panel of nine antibodies including CD34. Ultrastructurally, every GANT case showed diagnostic findings and evidence of skeinoid fibers, whereas immunohistochemically all except one were CD34 positive. Immunoreactivity for neuron-specific enolase, synaptophysin, and vimentin was a common occurrence as well. In conclusion, GANT seems to be more frequent than hitherto recognized, skenoid fibers are a regular feature of GANT, and a positive CD34 immunoreaction does not discriminate between GANT and other non-smooth muscle, non-schwannian neoplasms.     

Decision matrix for selection of patients for a home infusion therapy program

Managed care and escalating healthcare costs have affected all aspects of clinical practice. Today's practitioners must evaluate each patient and clinical situation to select the appropriate intravenous delivery venue to improve the chances of producing a satisfactory outcome. The IV venue discussed in this article will focus on the key elements of identifying patients who will benefit from receiving pharmacomedical services in a home infusion therapy program.     

Murine alpha-macroglobulins demonstrate divergent activities as neutralizers of transforming growth factor-beta and as inducers of nitric oxide synthesis. A possible mechanism for the endotoxin insensitivity of the alpha2-macroglobulin gene knock-out mouse

alpha2-Macroglobulin null mice demonstrate increased resistance to endotoxin challenge (Umans, L., Serneels, L., Overbergh, L., Van Leuven, F., and Van den Berghe, H. (1995) J. Biol. Chem. 270, 19778-19785). We hypothesized that this phenotype might reflect the function of murine alpha2M (malpha2M) as a neutralizer of transforming growth factor-beta (TGF-beta) and inducer of nitric oxide synthesis in vivo. When incubated with wild-type mouse plasma, TGF-beta1 and TGF-beta2 bound only to malpha2M. Alternative TGF-beta-binding proteins were not detected in plasma from alpha2M(-/-) mice. Wild-type mouse plasma, but not plasma from alpha2M(-/-) mice, inhibited TGF-beta1 binding to TGF-beta receptors on fibroblasts. Purified malpha2M bound TGF-beta1 and TGF-beta2 with similar affinity; the KD values were 28 +/- 4 and 33 +/- 4 nM, respectively. Murinoglobulin, the second murine alpha-macroglobulin, bound both TGF-beta isoforms with 30-fold lower affinity. Malpha2M counteracted the activities of TGF-beta1 and TGF-beta2 in an endothelial cell growth assay. Malpha2M also induced NO synthesis when incubated with RAW 264.7 cells, an activity which probably results from the neutralization of autocrine TGF-beta activity. Human alpha2M induced NO synthesis comparably to malpha2M; however, MUG had no effect. These studies demonstrate that the ability to neutralize TGF-beta is a property of malpha2M, which is not redundant in the murine alpha-macroglobulin family or in murine plasma. Malpha2M is the only murine alpha-macroglobulin that promotes NO synthesis. The absence of malpha2M, in alpha2M(-/-) mice, may allow TGF-beta to more efficiently suppress excessive iNOS expression following endotoxin challenge.     

Transverse glabellar flap for obliteration/isolation of the nasofrontal duct from the anterior cranial base

Management of fractures involving the nasofrontal duct region of the frontal sinus has focused on preserving function when possible or obliterating the sinus and duct when fracture patterns potentiate ductal obstruction and possible transcranial seeding of bacteria. When frontal sinus preservation is in doubt, controversy surrounds the use of cranialization versus obliteration, and the method of obliteration. Perioperative and late postoperative infections are uncommon, but their occurrence jeopardizes an often complex reconstruction and can be life threatening. This paper describes the design and indications for a pedicled transverse glabellar muscle flap for obliteration of the nasofrontal duct, thereby isolating the anterior cranial base from the aerodigestive system. This vascularized muscle flap utilizes the corrugator supercilii and procerus muscles, which are introduced into the sinus via a small, surgically created window in the superomedial orbital wall without disturbing the central facial aesthetic contours. Six patients with comminuted fractures at the nasofrontal duct level associated with displaced posterior frontal sinus fractures have been treated with the transverse glabellar flap. Follow-up ranges from 8 to 30 months. There have been no early or late postoperative complications. The transverse glabellar flap is a reliable and versatile method of partitioning the upper aerodigestive tract from the anterior cranial base with vascularized tissue, thus minimizing the risk of infectious complications. The resulting donor site deformity is more acceptable than that seen with the traditional pedicled galeal frontalis flap.