Anatomy, biomechanics, and pathomechanics of lesser digital deformities

This article discusses anatomy and normal biomechanics of the lesser digits. The pathomechanics that may lead to digital deformities or the hammered digit syndrome are discussed also. The importance of identifying the causes of the hammered digit syndrome prior to surgical correction is emphasized. Knowing the causes can help determine effective postoperative control that can neutralize the deforming forces.     

Characterization of the copper chaperone Cox17 of Saccharomyces cerevisiae

Assembly of functional cytochrome oxidase in yeast requires Cox17, which has been postulated to deliver copper ions to the mitochondrion for insertion into the enzyme. This role for Cox17 is supported by the observation that it binds copper as a binuclear cuprous-thiolate cluster. X-ray absorption spectroscopy, together with UV-visible absorption and emission spectroscopy, indicates the presence of bound cuprous ions, trigonally coordinated by thiolate ligands. Analysis of the EXAFS shows three Cu-S bonds at 2.26 A, plus a short Cu-Cu distance of 2.7 A, indicating a binuclear cluster in Cox17. The cuprous-thiolate cluster in Cox17 is substantially more labile than structurally related clusters in metallothioneins.     

Mass spectrometric analysis of 2-deoxyribonucleoside and 2'-deoxyribonucleotide adducts with aldehydes derived from lipid peroxidation

An important emerging issue in chemical carcinogenesis is the role that products of endogenous metabolism play in formation of covalently modified DNA. One example is the formation of alpha, beta-unsaturated aldehydes as a result of endogenous and drug-stimulated lipid peroxidation. Malondialdehyde (MDA), crotonaldehyde (CR), 2-hexenal (HX), and 4-hydroxy-2-nonenal (HNE) react covalently with 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) residues on DNA to form promutagenic cyclic adducts that may be important in the etiology of cancer in humans and animals. The accurate quantification of such adducts provides a powerful tool in molecular epidemiology for assessing carcinogenic risks from various lifestyle choices (e.g. diet, drug use) in humans. 32P-Postlabeling is recognized as one of the most sensitive methods available for detection of DNA adducts in human tissues, but without adequate validation such methodology can yield inaccurate quantitative measurements. We have used LC separations in conjunction with electrospray ionization MS and tandem MS (triple quadrupole and hybrid quadrupole-orthogonal acceleration time of flight analyzers) to characterize MDA-, CR-, HX- and HNE-modified dG and nucleotide (3'- and 5'-monophosphate; 3',5'-bisphosphate) adducts. These data have been used to validate 32P-postlabeling methods for quantification of low level MDA-dG adducts formed in DNA of human and animal tissues. Availability of reliable methods for quantification of endogenous DNA damage in humans and animals is essential for determining unknown etiologies of cancer and for the assessment of cancer risks in humans.     

Clinical correlates of circulating immune complexes and antibody reactivity in squamous cell carcinoma of the head and neck. The Department of Veterans Affairs Laryngeal Cancer Study Group

PURPOSE: To evaluate the correlation between the presence and titer of host-derived antibody reactivity, circulating immune complexes, and clinical course and prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: Serum samples, obtained from untreated patients with squamous cell carcinoma of the larynx entered onto a multiinstitutional trial, were evaluated for the presence of elevated circulating immune complexes (221 patients) and host-derived antibody directed against two SCCHN cell lines (107 patients). RESULTS: Patients had significantly elevated levels of circulating immune complexes as measured by C1q binding compared with normal controls. Patients with higher levels of circulating immune complexes were less likely to respond to chemotherapy. No correlations were noted between immune complex levels and stage of disease, nodal status, site of disease, recurrence, or survival. Evaluation of native antibody titers for their relationship to clinical correlates showed no statistically significant associations. In sera subjected to immune complex dissociation, patients with moderately or poorly differentiated tumors had significantly higher antibody titers when compared with patients with well-differentiated tumors. Because marked variation in the increase of antibody titers following immune complex dissociation was noted, the ratio of immune complex-dissociated to native antibody titer was examined. Patients with a high ratio had a lower proportion of complete and partial responses to chemotherapy. CONCLUSION: Our results support the conclusion that the formation of tumor-associated immune complexes in patients with SCCHN is associated with a decreased response to chemotherapy.     

Effects of the synthetic anti-oxidant, probucol, on the U937 monoblastoid cell line

We examined physiological events in the hyperplastic artery, using a method based on the mechanical responsiveness and myosin light-chain phosphorylation in response to various stimulants. Six weeks after endothelial denudation by ballooning of the right carotid artery, strips of this artery with moderate intimal hyperplasia (intimal area was 30-50% of medial area in 20 of 28 rabbits) were used for experiments. Strips from the left carotid served as the normal control. When the hyperplastic artery was stimulated with 30 microM PGF2 alpha, the maximal tension (232.4 +/- 49.1 mg/mg dry wt, mean +/- SD) was significantly higher (P < 0.05) than that of the control (129.5 +/- 16.4 mg/mg). The maximal extent of myosin light-chain monophosphorylation (45.4 +/- 8.9%) and diphosphorylation (10.9 +/- 5.2%) in the hyperplastic artery was significantly higher (P < 0.05) than that in the control artery (33.0 +/- 4.8 and 4.0 +/- 4.8%, respectively). The monophosphorylation of the myosin light chain in the hyperplastic artery was sustained for up to 20 min, while that in the control artery decreased to the basal level within 20 min. Similar observations were obtained by stimulation with 60 mM K+ or 30 microM norepinephrine. Dose-response curves of the development of tension in the hyperplastic artery to various agonists (K+, PGF2 alpha, norepinephrine) shifted upward the curves for the control artery. These results suggest that qualitative changes in the characteristics of smooth muscle cells may occur in the intimal hyperplastic portion, including a hyperreactive contraction associated with enhanced and sustained phosphorylation of the myosin light chain.     

How does gamma-interferon mediate resistance to Listeria monocytogenes?

Gamma-interferon (IFN-gamma) seems to be required for resistance to Listeria monocytogenes in vivo, but acts early in infection, before apparent T cell involvement. The early role of IFN-gamma is unknown, but might include enhancing antigen presentation, inducing secretion of tumor necrosis factor alpha and helping early precursor macrophages to express nonspecific listericidal activity.     

Non-penetrance and late appearance of polyps in families with familial adenomatous polyposis

One case of non-penetrance of the familial adenomatous polyposis (FAP) gene at 59 years of age and late onset of polyps on endoscopy and biopsy in this and two other families is described. Screening protocols should include dental screening as well as indirect ophthalmoscopy and endoscopy to detect minimal manifestations of the gene. In the absence of a specific DNA predictive test, bowel screening should continue well beyond 30 years of age.