The regulation of skin proliferation and differentiation in the IR null mouse: implications for skin complications of diabetes.

Impaired wound healing of skin is one of the most serious complications of diabetes. However, the pathogenesis of this process is not known, and it is unclear whether impaired insulin signaling could directly affect skin physiology. To elucidate the role of insulin in skin, we studied skin insulin receptor (IR) null mice. The morphology of the skin of newborn IR null mice was normal; however, these mice exhibited decreased proliferation of skin keratinocytes and changes in expression of skin differentiation markers. Due to the short life span of the IR null mice, further characterization was performed in cultured skin keratinocytes that can be induced to differentiate in vitro, closely following the maturation pattern of epidermis in vivo. It was found that despite a compensatory increase in the insulin-like growth factor I receptor autophosphorylation, differentiation of cultured IR null keratinocytes was markedly impaired. In vitro proliferation was not affected as much. Furthermore, although the basal glucose transport system of the null mice was not defective, the insulin-induced increase in glucose transport was abrogated. These results suggest that insulin regulates, via the IR, the differentiation and glucose transport of skin keratinocytes, whereas proliferation is affected by the diabetes milieu of IR knockout mice.

Sebaceous adenocarcinoma of meibomian gland origin with targetoid intra-nuclear inclusions.

Neoplastic proliferation of the meibomian glands is most often characterized by a tarsal tumor of the eyelid conjunctiva, having the clinical appearance of a chalazion. As such, the tumor is frequently not recognized as a neoplasm and is treated conservatively as an inflammatory lesion. A protracted clinical course combined with repeated surgical excisions typify this slow-growing tumor of sebaceous gland cells. In addition to the usual features of polygonal cell shape, abundant cytoplasm, and numerous fat vacuoles, we describe the presence of a peculiar nuclear inclusion seen only in the parenchymal cells of this tumor, and having the appearance of concentric layers of electron-dense material surrounding an opaque electron lucent core.

Liver abscess at the Hadassah University during years 1967-77.

The charts of 36 patients, 27 males and 9 females, with liver abscess diagnosed at the Hadassah University Hospital between 1967-1977 were reviewed. The patients ranged in age from two months to 80 years and 25 patients (69%) were older than 40 years. The diagnosis was initially suggested by liver scan in 18 patients (50%), and was first made at autopsy in six (17%). The time-lapse between the onset of illness and diagnosis ranged from one day to 13 months, with a bimodal distribution. Large solitary abscesses were diagnosed later than small multiple abscesses. Ten patients (28%) were admitted with fever as the only sign of illness; specific signs and laboratory evidence of liver involvement often occurred late in the course of the disease. In 15 patients (42%), the etiology was regarded as amebic. In patients with pyogenic abscesses, the most commonly isolated organisms belonged to the normal bowel flora and biliary tract disease was present in 62% (13/21) of these patients. The overall mortality rate was 31%. This survey stresses the need for an increased awareness of the subtle presentation of liver abscess.

Stimulation of virus production and induction of self-syncytium formation in human T-cell leukemia virus type I- and type II-infected T cells by 12-O-tetradecanoylphorbol-13-acetate.

Treatment of human T-cell leukemia virus type I (HTLV-I)- and HTLV-II-infected T-cell lines with 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated virus release. However, this stimulation was mainly detected at 42 to 48 h of treatment, whereas later virus release declined rapidly. During the first 48 h, TPA had no effect on cell growth, but later, the number of viable cells was profoundly lower in the TPA-treated than in the untreated cultures. This shift in virus release and cell number resulted from self-fusion of a large proportion of the virus-producing cells, which seemed to consequently enter into a dying process. This fusion, which resulted in syncytium formation, was strongly inhibited by anti-HTLV-I env monoclonal antibodies. Furthermore, no self-fusion was detected in three different uninfected T-cell lines similarly treated with TPA. On the other hand, stimulation of virus production by 3-methylcholanthrene (3-MC) treatment failed to induce self-fusion in the infected cells. Moreover, no syncytium was detected when these 3-MC-treated infected cells were cocultured with any of the TPA-treated uninfected cells. The effects of TPA on virus production and syncytium formation were both abolished by three different protein kinase C inhibitors. Taken together, these data suggest that the self-fusion observed in these experiments required both enhanced virus production and protein kinase C-phosphorylated viral or/and virally induced cellular component(s).