Influence of craniofacial surgery on the social attitudes toward the malformed and their handling in different cultures and at different times: a contribution to social world history

A historic overview including the European, American, Asian, and African continents is given on attitudes toward and the handling of humans with congenital malformations in ancient cultures and on pertinent customs in some prehistoric peoples. Figures of early works of art showing malformed individuals are presented testifying to this worldwide and timeless problem of humankind. In parallel, analogous patient photographs from our hospital before and after reconstructive surgery are shown. Philosophies of ancient Greece, rome, and China on the subject of malformed infants essentially did not differ from the known attitudes of the less developed tribes in Europe and pre-Columbian America, although the means of elimination of unwanted offspring were rather passive (exposure) than active (manual killing). A radical change in attitudes and practices occurred with the spread of the Christian religion and its political installment in Europe. The care for the underprivileged including the malformed ones was considered a Christian duty to be performed with compassion and love. In our century, the clocks have been and apparently are turned back again. Atheistic and Darwinian influences, political atheism, and the belief in "higher ethics" issued by "superman" have led to a relapse into barbarism, also within the medical system. We, as craniofacial surgeons, are privileged to have the means to turn the clocks forward again by rehabilitating the physically most underprivileged: those with conspicuous craniofacial malformations. The necessary techniques exist and are applied, as the figures of patients from our hospital demonstrate, but the will and the emotional strength for their consequent application require more than our hands.     

Comparison of autochthonous and allogeneic breast-tumour cells in tests for lymphocyte immunity to human tumours

Lymphocytes from 10 patients with breast carcinoma were seeded in autologous serum, on autochthonous tumour cells and allogeneic tissue-cultured breast tumour cell lines. In 4 patients, the anti-tumour cell cytotoxicity against at least one of 3 breast tumour cell lines differed significantly from that against autochthonous tumour cells. Further study of these 4 individuals (using their previously frozen lymphoid cells and sera) showed that these differences occurred because serum which decreased ("blocked") lymphocyte anti-tumour cytotoxicity when applied to one tumour cell line, could either have no effect or potentiate it when applied to another, without any consistent pattern vis-à-vis target-cell susceptibility to these different humoral effects.     

Primary Aldosteronism and Resistant Hypertension: A Pathophysiological Insight

Primary aldosteronism (PA) is a pathological condition characterized by an excessive aldosterone secretion; once thought to be rare, PA is now recognized as the most common cause of secondary hypertension. Its prevalence increases with the severity of hypertension, reaching up to 29.1% in patients with resistant hypertension (RH). Both PA and RH are “high-risk phenotypes”, associated with increased cardiovascular morbidity and mortality compared to non-PA and non-RH patients. Aldosterone excess, as occurs in PA, can contribute to the development of a RH phenotype through several mechanisms. First, inappropriate aldosterone levels with respect to the hydro-electrolytic status of the individual can cause salt retention and volume expansion by inducing sodium and water reabsorption in the kidney. Moreover, a growing body of evidence has highlighted the detrimental consequences of “non-classical” effects of aldosterone in several target tissues. Aldosterone-induced vascular remodeling, sympathetic overactivity, insulin resistance, and adipose tissue dysfunction can further contribute to the worsening of arterial hypertension and to the development of drug-resistance. In addition, the pro-oxidative, pro-fibrotic, and pro-inflammatory effects of aldosterone may aggravate end-organ damage, thereby perpetuating a vicious cycle that eventually leads to a more severe hypertensive phenotype. Finally, neither the pathophysiological mechanisms mediating aldosterone-driven blood pressure rise, nor those mediating aldosterone-driven end-organ damage, are specifically blocked by standard first-line anti-hypertensive drugs, which might further account for the drug-resistant phenotype that frequently characterizes PA patients.     

Activation of DNA synthesis and expression of the JE gene by catalase in mouse osteoblastic cells: possible involvement of hydrogen peroxide in negative growth regulation

Type I diabetes susceptibility genes have been identified within the major histocompatibility complex (MHC) on chromosome 6p21.3 and near the VNTR/insulin region on chromosome 11p15.5. We have used polymorphic dinucleotide repeat markers to search the human genome for additional susceptibility genes in 162 type I diabetic families with an affected sibling pair. We report that an additional susceptibility gene is located on chromosome 2q31 near HOXD8 (P < 10(-5), maximum logarithm of odds score = 4.8) in an analysis of affected sibling pairs having specific human leukocyte antigen (HLA) and hypervariable nucleotide tandem repeat (VNTR)/insulin gene haplotypes (absence of high-risk HLA-DR3/4 haplotypes and presence of homozygous high-risk class I VNTR alleles). These results suggest the interaction of a minimum of three genes in the pathogenesis of type I diabetes in humans.     

Curcumin induces apoptosis in immortalized NIH 3T3 and malignant cancer cell lines

Curcumin, which is a widely used dietary pigment and spice, has been demonstrated to be an effective inhibitor of tumor promotion in mouse skin carcinogenesis. We report that curcumin induces cell shrinkage, chromatin condensation, and DNA fragmentation, characteristics of apoptosis, in immortalized mouse embryo fibroblast NIH 3T3 erb B2 oncogene-transformed NIH 3T3, mouse sarcoma S180, human colon cancer cell HT-29, human kidney cancer cell 293, and human hepatocellular carcinoma Hep G2 cells, but not in primary culture of mouse embryonic fibroblast C3H 10T1/2, rat embryonic fibroblast, and human foreskin fibroblast cells in a concentration- and time-dependent manner. Many cellular and biochemical effects of curcumin in mouse fibroblast cells have been reported, such as inhibition of protein kinase C (PKC) activity induced by phorbol 12-myristate 13-acetate treatment, inhibition of tyrosine protein kinase activity, and inhibition of arachidonic acid (AA) metabolism. Treatment of NIH 3T3 cells with the PKC inhibitor staurosporine, the tyrosine kinase inhibitor herbimycin A, and the AA metabolism inhibitor quinacrine induces apoptotic cell death. These results suggest that, in some immortalized and transformed cells, blocking the cellular signal transduction might trigger the induction of apoptosis.     

Evaluation of Vitek GPS-SA card for testing of oxacillin against borderline-susceptible staphylococci that lack mec

Fifty-one Staphylococcus aureus strains lacking mec for which oxacillin MICs were 1 to 8 micrograms/ml were tested against oxacillin and the combination of oxacillin and clavulanic acid with the Vitek GPS-SA card, the reference broth microdilution method, and the oxacillin agar screen plate. Of the 51 strains, 44 (86%) did not grow on the oxacillin agar screen plate, broth microdilution MICs were 1 to 2 micrograms/ml, and GPS-SA card MICs were < or = 2 micrograms/ml, with the exception of 3 strains that failed to grow in the card on repeated attempts. Another seven strains did grow on the oxacillin agar screen plate. For four of the latter group of strains, oxacillin broth microdilution MICs were > 4 micrograms/ml and GPS-SA card MICs were > or = 4 micrograms/ml; for the other 3 strains, corresponding MICs were 4 and < or = 2 micrograms/ml, respectively. The GPS-SA card classified 86% of strains as oxacillin susceptible.     

Catalytic Rearrangement of Epoxide Compounds

Products formed by rearrangement of epoxide compounds provide useful intermediates in organic syntheses and some of them are valuable as raw materials in the chemical industry. Many studies on the catalytic rearrangement of the epoxides have been made. The reactions which have been used most frequently are homogeneous with acid or base catalysts such as BF3, MgBr2, t-BuOK, or lithium dialkylamides; the acid catalysts form mainly carbonyl compounds (ketone and aldehyde) and the base catalysts in most cases yield allylic alcohols. Recently the heterogeneous reaction over solid catalysts was also investigated, but the catalysts used were just alumina and silica gel, solid acid and base catalysts, and it is very recent that various kinds of the solid acids and bases have been used as catalysts for epoxide isomerization, especially by the authors (Section VI-A). Studies with molten salts are few, and investigations with metal complex and organometal catalysts have just begun.     

Fabrication and Mechanical Properties of Continuously Graded MoSi2–ZrO2(2Y) Materials Using Wet-Molding

Continuously graded MoSi₂-ZrO₂(2Y) materials with high density (97.5% of theoretical) have been fabricated by uniaxial wet-molding, followed by hot pressing (1000°C/1 h/30 MPa) and hot isostatic pressing (1400°C/2 h/196 MPa). Their composition profiles are greatly influenced by the viscosity of mixed solutions of glycerin and ethanol used as a dispersion medium; a linear compositional gradient from MoSi₂/ZrO₂(2Y) 70/30 to 20/80 mol% is obtained from the solution (50/50 vol%) with a viscosity of 20 mPa s. Vickers hardness (Hv) and fracture toughness (KIC) increase from 9.7 to 12.4 GPa and from 5.1 to 12.5 MPa m1/2, respectively, with increasing ZrO₂(2Y) composition.     

Lethal effect of the expression of a killer gene SMK1 in Saccharomyces cerevisiae

Expression of the SMK1 gene which encodes the yeast killer toxinSMKT is lethal in Saccharomyces cerevisiae. Effects of deletionand site-directed mutagenesis of SMK1 on the lethality and thesecretion of the gene products were examined. Deletion of theinterstitial     

Prolongation of allograft survival by 1,25-dihydroxyvitamin D3

BACKGROUND: 1,25-Dihydroxyvitamin D3, the hormonal form of vitamin D, is now believed to play a significant role in the immune responses, both in vitro and in vivo, preventing the development of several autoimmune diseases. These studies suggest that 1,25-dihydroxyvitamin D3 may be effective in prolonging allograph survival. METHODS: To test the hypothesis that 1,25-dihydroxyvitamin D3 would prolong allograft survival, neonatal heart grafts were transplanted to allogeneic recipients receiving either 19-nor-1,25-dihydroxyvitamin D2 (200 ng/day) or 1,25-dihydroxyvitamin D3 (50 ng/mouse/day) orally through the diet. The efficacy of 1,25-dihydroxyvitamin D3 in prolonging graft survival in a vascularized model was determined by heterotopic ACI to Lewis heart transplants. RESULTS: The provision of exogenous 1,25-dihydroxyvitamin D3 or an analog, 19-nor-1,25-dihydroxyvitamin D2, to mice markedly prolonged the survival of neonatal mouse heart allografts. Similar results were obtained with a vascularized heterotopic heart transplant model in rats. Cyclosporine at a maximum 25 mg/kg dose for mice proved less effective than 1,25-dihydroxyvitamin D3. Graft survival in mice differing at class I and class II loci (B10.A(4R) --> C57BL/10) increased from 13.0+/-1.1 days to 51.0+/-5.6 days and was significantly better than cyclosporine monotherapy (33.2+/-3.6). Rat heart survival in a high responder strain combination (ACI --> Lewis) increased from 6.2+/-0.3 to 25.2+/-2.8 days. The increased survival of the transplants brought about with 1,25-dihydroxyvitamin D3 was not accompanied by hypercalcemia in rats. CONCLUSION: These results suggest that 1,25-dihydroxyvitamin D3 can be used as an effective agent in preventing graft rejection.