Faculty Bibliography

Clinical and radiographic follow-up was performed on a consecutive series of 105 patients who underwent 120 total hip arthroplasties at the authors' institution from 1983 to 1988 with a straight, cobalt-chrome femoral stem implanted using a second-generation cementing technique. The mean age at the time of surgery was 68.5 years, and the mean follow-up was 16 years. At 16 years' follow-up, the prevalence of revision for aseptic loosening of the Spectron femoral component was only 4.2%; 5 stems were revised for aseptic loosening at a mean of 10.2 years after implantation. Sixteen-year survivorship of the component was 93.9% +/- 2.7% when revision for aseptic loosening was taken as the endpoint or 90.3% +/- 4.4% when either revision for aseptic loosening or radiographic evidence of loosening was taken as the endpoint

UV light, a paradigmatic initiator of cell stress, invokes responses that include signal transduction, activation of transcription factors, and changes in gene expression. Consequently, in epidermal keratinocytes, its principal and frequent natural target, UV regulates transcription of a distinctive set of genes. Hypothesizing that UV activates distinctive epidermal signal transduction pathways, we compared the UV-responsive activation of the JNK and NFkappaB pathways in keratinocytes, with the activation of the same pathways by other agents and in other cell types. Using of inhibitors and antisense oligonucleotides, we found that in keratinocytes only UVB/UVC activate JNK, while in other cell types UVA, heat shock, and oxidative stress do as well. Keratinocytes express JNK-1 and JNK-3, which is unexpected because JNK-3 expression is considered brain-specific. In keratinocytes, ERK1, ERK2, and p38 are activated by growth factors, but not by UV. UVB/UVC in keratinocytes activates Elk1 and AP1 exclusively through the JNK pathway. JNKK1 is essential for UVB/UVC activation of JNK in keratinocytes in vitro and in human skin in vivo. In contrast, in HeLa cells, used as a control, crosstalk among signal transduction pathways allows considerable laxity. In parallel, UVB/UVC and TNFalpha activate the NFkappaB pathway via distinct mechanisms, as shown using antisense oligonucleotides targeted against IKKbeta, the active subunit of IKK. This implies a specific UVB/UVC responsive signal transduction pathway independent from other pathways. Our results suggest that in epidermal keratinocytes specific signal transduction pathways respond to UV light. Based on these findings, we propose that the UV light is not a genetic stress response inducer in these cells, but a specific agent to which epidermis developed highly specialized responses

A 13-year-old boy and a 7-year-old boy, who are brothers, presented with a life-long history of erythema, hyperkeratosis, and desquamation of the hands and feet. Symptoms improved with the use of topical glucocorticoids and keratolytics. PPK of Sybert is characterized by palmoplantar hyperkeratosis with transgrediens, autosomal dominant inheritance, and the absence of associated systemic features

Microvascular free-tissue transfer has been a major advance in the treatment of complex traumatic defects of the upper extremity. One hundred and fifty microvascular free-tissue transfers were performed in 133 patients with complex traumatic upper extremity defects at Bellevue Hospital Center from 1976 to 2000. The indication for microvascular free tissue transfers was exposure of vital structure (81 percent), bone defect (11 percent), and functional deficit (8 percent). The parascapular region was the most common donor site used (26 percent). Microvascular free-tissue transfer was performed either emergently at the time of injury (9.3 percent), during days 1 to 5 post injury (19.3 percent), during days 6 to 21 (19.3 percent), or after day 21 (52 percent). The overall flap failure rate was 9 percent. A decreased incidence of flap failure was observed in patients treated from 6 to 21 days post injury (3 percent p<0.05). The most common acute complication was infection at the recipient site, observed in 14 percent of patients overall. A decreased incidence of recipient-site infection was seen in patients who received free flaps at days 6 to 21 (3 percent; p<0.05). In long-term follow-up, the incidences of osteomyelitis and nonunion were lowest in patients treated from 6 to 21 days post injury (0.0 percent and 11 percent, respectively; p<0.05). During the last 10 years, the timing of reconstruction has been altered, and now preferentially microvascular free flaps are performed 6 to 21 days post injury. The treatment algorithm has been simplified and now only four different flaps are used in the majority of patients (70 percent). With this, the authors have witnessed a decrease in failure rates from 11 percent to 4 percent, a decrease in recipient-site infections from 16 percent to 10 percent and a decrease in osteomyelitis from 12 percent to 4 percent. The preferred timing for microvascular free-tissue transfers to the upper extremity is concluded to be 6 to 21 days post injury

Platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A2 associated with lipoproteins that hydrolyzes platelet-activating factor (PAF) and oxidized phospholipids. We have developed an ELISA for PAF-AH that is more sensitive than previous methods, and have quantified HDL-associated and non-HDL-associated PAF-AH in healthy, hyperlipidemic, and diabetic subjects. In healthy subjects, plasma total PAF-AH concentration was positively correlated with PAF-AH activity and with plasma total cholesterol, triacylglycerol, LDL cholesterol and apolipoprotein B (apoB) concentrations (all P < 0.01). HDL-associated PAF-AH concentration was correlated positively with plasma apoA-I and HDL cholesterol. Subjects with hyperlipidemia (n = 73) and diabetes mellitus (n = 87) had higher HDL-associated PAF-AH concentrations than did controls (P < 0.01). Non-HDL-associated PAF-AH concentration was lower in diabetic subjects than in controls (P < 0.01). Both hyperlipidemic and diabetic subjects had lower ratios of PAF-AH to apoB (P < 0.01) and higher ratios of PAF-AH to apoA-I (P < 0.01) than did controls. Our results show that the distribution of PAF-AH mass between HDLs and LDLs is determined partly by the concentrations of the lipoproteins and partly by the mass of enzyme per lipoprotein particle, which is disturbed in hyperlipidemia and diabetes mellitus

Mineralization often occurs in areas of apoptotic changes. Our findings indicate that physiological mineralization is mediated by matrix vesicles. These matrix vesicles use mechanisms to induce mineralization that are different from the mechanisms used by apoptotic bodies released from apoptotic cells. Therefore, different therapeutic approaches must be chosen to inhibit pathological mineralization depending on the mechanism of mineralization (matrix vesicles versus apoptotic bodies). INTRODUCTION: Physiological mineralization in growth plate cartilage is restricted to regions of terminally differentiated and apoptotic chondrocytes. Pathological mineralization of tissues also often occurs in areas of apoptosis. We addressed the question of whether apoptotic changes control mineralization events or whether both events are regulated independently. METHODS: To induce mineralization, we treated growth plate chondrocytes with retinoic acid (RA); apoptosis in these cells was induced by treatment with staurosporine, anti-Fas, or TNFalpha. The degrees of mineralization and apoptosis were determined, and the structure and function of matrix vesicles and apoptotic bodies were compared. RESULTS: Release of matrix vesicles and mineralization in vivo in the growth plate occurs earlier than do apoptotic changes. To determine the functional relationship between apoptotic bodies and matrix vesicles, growth plate chondrocytes were treated with RA to induce matrix vesicle release and with staurosporine to induce release of apoptotic bodies. After 3 days, approximately 90% of staurosporine-treated chondrocytes were apoptotic, whereas only 2-4% of RA-treated cells showed apoptotic changes. RA- and staurosporine-treated chondrocyte cultures were mineralized after 3 days. Matrix vesicles isolated from RA-treated cultures and apoptotic bodies isolated from staurosporine-treated cultures were associated with calcium and phosphate. However, matrix vesicles were bigger than apoptotic bodies. Furthermore, matrix vesicles but not apoptotic bodies contained alkaline phosphatase and Ca2+ channel-forming annexins II, V, and VI. Consequently, matrix vesicles but not apoptotic bodies were able to take up Ca2+ and form the first mineral phase inside their lumen. Mineralization of RA-treated cultures was inhibited by antibodies specific for annexin V but not mineralization of staurosporine-treated cultures. CONCLUSION: Physiological mineralization of growth plate chondrocytes is initiated by specialized matrix vesicles and requires alkaline phosphatase and annexins. In contrast, mineral formation mediated by apoptotic bodies occurs by a default mechanism and does not require alkaline phosphatase and annexins

The vertebrate vascular system is essential for the delivery and exchange of gases, hormones, metabolic wastes and immunity factors. These essential functions are carried out in large part by two types of anatomically distinct blood vessels, namely arteries and veins. Previously, circulatory dynamics were thought to play a major role in establishing this dichotomy, but recently it has become clear that arterial and venous endothelial cells are molecularly distinct even before the output of the first embryonic heartbeat, thus revealing the existence of genetic programs coordinating arterial-venous differentiation. Here we review some of the molecular mechanisms involved in this process

Horizontal gene transfer (HGT) spreads genetic diversity by moving genes across species boundaries. By rapidly introducing newly evolved genes into existing genomes, HGT circumvents the slow step of ab initio gene creation and accelerates genome innovation. However, HGT can only affect organisms that readily exchange genes (exchange communities). In order to define exchange communities and understand the internal and external environmental factors that regulate HGT, we analyzed approximately 20,000 genes contained in eight free-living prokaryotic genomes. These analyses indicate that HGT occurs among organisms that share similar factors. The most significant are genome size, genome G/C composition, carbon utilization, and oxygen tolerance.