Differential expression of cdk inhibitors p16, p21cip1, p27kip1, and cyclin E in cervical cytological smears prepared by the ThinPrep method.

Our objective was to correlate p16, p21cip1, p27kip1, and cyclin E protein expression with the degree of dysplasia on ThinPrep Papanicolaou (Pap) smears using a modified immunoperoxidase staining. Smears read as normal, atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), or high-grade SIL (HSIL) were identified and tested for high-risk human papillomavirus (HR-HPV). Additional smears were processed for immunoperoxidase for p16, p21cip1, p27kip1, and cyclin E. Thirty-four smears were satisfactory for study. The p16 was positive in all nine HSIL, in four of nine LSIL, and in one of seven ASC-US. The p27kip1 was positive in all nine HSIL, in eight of nine LSIL, and in one of seven ASC-US. The p21cip1 was positive in all nine HSIL, in one of nine LSIL, and in one of seven ASC-US. Cyclin E was positive in seven of nine HSIL and in one of nine LSIL and in none of the ASC-US smears. Normal smears were negative for all the antigens. There was poor correlation of protein expression and HR-HPV infection. We concluded that p16, p21cip1, p27kip1, and cyclin E can be demonstrated on Pap smears and they are expressed differentially in dysplastic cells, with highest expression in HSIL. The p21cip1 and cyclin E showed the greatest correlation with HSIL.

Protein kinase B, P34cdc2 kinase, and p21 ras GTP-binding in kidneys of aging rats.

Renal nephropathy present in male Wistar rats more than 13 months of age was reported as an indication that the rats were in renal failure. In this study, the renal tissue damage at 14 months of age in male Munich Wistar rats was similar to that reported for Wistar rats, indicating that Munich Wistar rats could be another model for study of kidney function in the aging rat. The usual renal response to injury involves increased cell division and/or reparative processes that involve tyrosine kinase activity (TyrK) and/or guanosine triphosphate-binding (G) protein signal trans-duction pathways. This study reveals the presence of renal tissue damage coinciding with significantly reduced activity of Ras, Akt, and p34cdc2 kinase, the signaling proteins that regulate cell division and/or growth, in renal cortical tissues of aging rats compared to young rats (P < 0.005, P < 0.005, and P< 0.001, respectively). These results suggest that proteins involved in signal transduction pathways associated with cell replication are downregulated in the aging kidney cortex at a time when renal cellular damage is also present.

Vascular inflammation (vasculitis) in sweet syndrome: a clinicopathologic study of 28 biopsy specimens from 21 patients.

BACKGROUND: Sweet syndrome is characterized by painful, erythematous plaques of rapid onset accompanied by fever. Absence of vasculitis is a histologic criterion for diagnosis. However, recent reports suggest that vasculitis should not exclude the diagnosis. We hypothesized that vasculitis can occur in Sweet syndrome and that it represents an epiphenomenon rather than a primary immune-mediated process. DESIGN: Skin biopsy specimens from patients with Sweet syndrome were reviewed to determine the prevalence of vasculitis. The clinicopathologic features of cases with vasculitis were evaluated for statistically significant associations. Specimens with vasculitis underwent immunofluorescence staining. SETTING: University department of dermatology, university hospital, and private practice. PATIENTS: Medical records and biopsy specimens of 21 patients meeting diagnostic criteria for Sweet syndrome were reviewed. INTERVENTIONS: None. RESULTS: The prevalence of vasculitis was 29% (6 of 21 patients). There was a significant association of vasculitis with lesions of longer duration (P =.02). Vascular immunoglobulin and complement could not be demonstrated in cases of Sweet syndrome with vasculitis. CONCLUSIONS: Vasculitis is not a primary, immune-mediated process in Sweet syndrome but occurs secondary to noxious products released from neutrophils. Blood vessels in lesions of longer duration are more likely to develop vasculitis than those of shorter duration because of prolonged exposure to noxious metabolites. Vasculitis does not exclude a diagnosis of Sweet syndrome.