Electron microscopy evidence that cytoplasmic localization of the p16(INK4A) "nuclear" cyclin-dependent kinase inhibitor (CKI) in tumor cells is specific and not an artifact. A study in non-small cell lung carcinomas.

It is well established that p16(INK4A) protein acts as a cell cycle inhibitor in the nucleus. Therefore, cytoplasmic localization of p16 (INK4A) usually is disregarded by investigators as nonspecific. Three recent studies reported findings that differ from the current view concerning p16(INK4A) immunohistochemical localization. All three demonstrated that breast and colon cancers expressing cytoplasmic p16(INK4) represent distinct biological subsets. We previously detected in a percentage of non-small cell lung carcinomas simultaneous nuclear and cytoplasmic p16(INK4A) staining. In view of the reports concerning breast and colon carcinomas, we conducted an ultrastructural re-evaluation of our cases to clarify the specificity of p16(INK4A) cytoplasmic expression. We observed p16 (INK4A) immunolocalization in both the nucleus and the cytoplasm of a proportion of tumor cells. Diffuse dense nuclear staining was detected in the nucleoplasm, whereas weaker granular immunoreactivity was observed in the cytoplasm near the rough endoplasmic reticulum. Negative tumor cells also were visible. In the tumor-associated stromal, cells p16(INK4A) immunoreactivity was detected only in the nuclei. We have demonstrated that p16(INK4A) cytoplasmic staining is specific and suggest that it represents a mechanism of p16(INK4A) inactivation similar to that observed in other tumor suppressor genes.

Fat injections for facial rejuvenation: 17 years experience in 1720 patients.

BACKGROUND: Autologous adipose tissue has been proved to be an excellent filling material. Fat injections can correct cosmetic defects that are caused by loss of subcutaneous tissue, such as atrophy of the face due to significant weight loss, wrinkles and facial involution due to ageing. OBJECTIVE: To evaluate the safety and long-term results of facial rejuvenation by autologous fat injections using the fine-needle technique to inject fat and frozen fat for repeating the implantation procedure. METHOD: Patients were evaluated clinically and photographically. Extraction, processing and implantation of fat were performed using an anaerobic technique. The fat was harvested by tumescent liposuction, using syringes and small diameter blunt-tip cannulas (2-3 mm). After washing the collected fat in normal saline it was centrifuged, transferred to small syringes (1-2.5 mL diameter) and then injected subcutaneously using fine needles of 21-23 G. Hypercorrection was avoided, so one or two repetitions of the fat injections were usually necessary, at intervals of at least 1 month, in order to achieve the desired cosmetic result. Using frozen fat simplified repeat fat implantation. RESULTS: The clinical long-term follow-up of 1720 patients up to 17 years is presented. Absorption of the injected fat was estimated at 40-60%. The absorption rate varied a lot in each case. Long-term follow-up proved that final correction after two or more repetitions of frozen fat injections, persisted for many years, the longest proved to be more than 12 years. CONCLUSIONS: The advantages of the fine-needle technique for fat grafting were very important: more accurate and refined work, less painful injections, no scars at needle puncture points, early treatment of small defects, and the facility to treat multiple sites, even the entire face, in one session. There were no major complications. Oedema and sometimes echymoses at the donor site for 6-10 days and slight bruising at the injected areas for 3-5 days are the disadvantages of the procedure.

A histological and immunohistochemical study of medical-grade fluid silicone.

BACKGROUND: Medical-grade injectable silicone for use in soft tissue augmentation is administered subcutaneously by injections of the pure material. OBJECTIVE: To examine histologically and immunohistochemically the characteristics of medical-grade silicone and to identify the advantages and disadvantages of the serial puncture technique. RESULTS: In early biopsies, perivascular lymphocytic infiltration with the characteristic reaction of delayed hypersensitivity (doses, 0.05-0.07 mL) was observed. Immunohistochemically, small local deposits of IgG and IgA were observed around the walls of small vessels. In later biopsies, the inflammation had progressed to a fibroblastic reaction. Additionally, the implantation of large doses provoked giant cell granulomas. CONCLUSIONS: Small doses (0.05-0.07 mL) of injected silicone produce an immunologic and fibroblastic reaction in the skin. The use of this substance with the serial puncture technique is not hazardous when proper technique is used.