[Bowen's disease, Paget's disease and basalioma of the anal region].
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Biomedical subjects
Publications and source records attributed to E Gross.
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The direct contact between amalgam and cast metal may enhance electrochemical reactions. In a study to determine the amount of mercury released in these reactions, six cast metal alloys with increasing precious metal contents were placed in immediate contact (contact area 10 mm2) to two non-gamma 2-amalgams (Amalcap, Valiant) and incubated with artificial saliva at 37 degrees C for up to 8 weeks; then the salivary mercury concentrations were measured. After the end of the incubation period the case metal surfaces were analyzed by ESCA for metal appositions. The results showed that direct contact between amalgam and cast metal after storage in artificial saliva for 8 weeks resulted in a minor release of mercury (22.7 +/- 10.63 ng/ml Hg). On the cast metal plates themselves only smallest mercury concentrations could be demonstrated. These in vitro tests have shown again that, although charge transfers do occur when different metals are in direct contact, they do so only to a minor degree, because of the passivation processes involved.
12-Hydroxyeicosatetraenoic acid (HETE) is associated with a variety of inflammatory conditions. For studies on pathophysiological function of 12-HETE, metabolically more stable analogs of 12-HETE would be useful. We biologically synthesized 20,20,20-trifluoro-12-HETE (20-F3-12-HETE) by incubating enantioselectively synthesized 20,20,20-trifluoro-arachidonic acid with human platelets. The product was identified by UV absorption spectrophotometry and gas chromatography-mass spectrometry. When 1 microgram 20-F3-12-HETE was incubated with 5 X 10(6) human neutrophils for 45 min, only 5% of the analog was metabolized while 66% of 12-HETE was metabolized in the same incubation condition. With 2 X 10(7) neutrophils, 37% of the analog was metabolized at the same incubation condition while 87% of 12-HETE was metabolized. Thus, by blocking omega-oxidation of 12-HETE with fluorine atoms, the stability of 12-HETE was greatly increased. This result indicates that the omega-oxidation is a major pathway for 12-HETE metabolism. The analog demonstrated as much chemotactic activity on human neutrophils as 12-HETE, and binding affinity of the analog for 12-HETE receptor in human epidermal cell was equal to that of 12-HETE. An analog of 12-HETE, which has extended metabolic stability without alteration of neutrophil chemotactic activity and binding affinity, would be a useful tool for studies on pathophysiological role of 12-HETE in inflammatory conditions.
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Since 1987 we perform a new technique of colorectal anastomosis in 6 babies resected because of severe Hirschsprung's disease. The operation was done electively in the seventh to eight month of age. In the method of the so-called compression anastomosis the instrument is inserted through the anorectal canal at the head fitted with two plastic rings (see illustrations). In the rectal stump the instrument is opened up, the rectal bowel edge is slipped over the distal ring. The prepared proximal bowel edge is slipped over the second white coloured ring. The rings are approached to one another and the instrument is released. The knife on the inside cuts the bowel. The two rings are then joined by means of springs. The compression anastomosis is completed. The two bowel edges are joined by compression via the two intraluminal plastic rings. These rings will pass spontaneously with the faeces days after operation. The diameter of the rings is 18 mm. Different diameters are available. Our good experiences in more than 160 compression anastomoses in colorectal surgery of adults encouraged us to use the method also in children. We saw one complication of a rectovaginal fistula 4 weeks after the operation followed by a severe stenosis of the anastomosis. The passing of the plastic rings was without any problem in all the cases. In the follow-up a bouginage was required only in the case mentioned above.
The arachidonic acid metabolite 12-hydroxyeicosatetraenoic acid (12-HETE) is assumed to play an important role in skin physiology and pathophysiology. Specifically, it has recently been discussed as a growth promoting agent in keratinocytes. Our aim was to find out whether epidermal cells possess specific receptors for 12-HETE which would mediate the effects of this eicosanoid in skin, including the putative growth stimulating activity. We could identify specific binding sites for 12(S)-HETE on the human epidermal cell line SCL-II. The analysis of binding data revealed a single class of binding sites with a Kd of 2,6 nM and a Bmax of 216,000 sites per cell. The binding was saturable, readily reversible, and specific for 12(S)-HETE with lower affinities for other monoHETE. We failed to detect any significant proliferative activity of 12(S)-HETE in the same epidermal cell line, although we applied three independent methods for evaluation of cell growth and used a concentration of 12(S)-HETE which should enable an optimal receptor occupancy. Thus, epidermal cells possess high-affinity 12(S)-HETE binding sites which are likely to be involved in the effects of this eicosanoid in epidermis. However, biologic effects other than direct growth stimulation seem to be transduced by 12(S)-HETE receptors in epidermal cells which need further investigation.
The molecular diagnosis of Gaucher disease has been difficult due to the existence of several different point mutations in the glucocerebrosidase gene and due to the presence of a tightly linked, highly homologous pseudogene. We now report the occurrence of a "Lepore-like" glucocerebrosidase fusion gene in which the 5' end is the functional gene and the 3' end is the pseudogene. This further complicates the molecular diagnosis of Gaucher disease but sheds light on the molecular anatomy of the glucocerebrosidase gene complex and on the pathogenesis of this important storage disease.
Gaucher disease is due to mutations involving the glucocerebrosidase gene. A closely homologous pseudogene is located approximately 16 kD downstream from the functional gene. Sequence analysis of clones from cDNA libraries made from skin fibroblast cultures showed several independent clones with the sequence of an aberrantly processed pseudogene message. Examination of cellular RNA from lymphoblasts or fibroblasts obtained from thirteen Gaucher disease patients, one Gaucher disease heterozygote, and four normal subjects showed that the pseudogene was consistently transcribed, and that in some cases the level of transcription seemed to be approximately equal to that of the functional gene. The transcription of the pseudogene must be taken into account when attempting to detect mutations of glucocerebrosidase by the study of cDNA libraries.
The polymerase chain reaction was used to detect four mutations in the DNA of 47 unrelated patients with type I Gaucher's disease (94 Gaucher's disease alleles). Two of the mutations, 1226 and 1448, and a new mutation (XOVR) representing cross-over between the glucocerebrosidase gene and its closely linked pseudogene, were found. There were five genotypes--namely, 1226/1226, 1226/1448, 1226/XOVR, 1226/?, and ?/? (where "?" indicates that none of the four known mutations was present). Severity of the disease was assessed with a scoring index according to age at diagnosis and extent of organ involvement. Mutation 1226 was associated with a mild clinical phenotype, and mutation 1448 with a more severe phenotype. Mutation 1226 is the most common cause of Gaucher's disease in Jewish patients.
Spectroscopic techniques were employed to establish the first comparative evaluation of the partition of the photosensitizers hematoporphyrin derivative (HPD) and photofrin II (PF-II) into phosphatidylcholine (PC) and PC/cholesterol liposomes. The fluorescence of the dyes was monitored while they were titrated with liposomes, yielding the dyes' effective binding constants to the membranes. The binding constants of HPD and PF-II to PC liposomes are 12.2 +/- 0.3 (mg/ml)-1 and 9.2 +/- 0.8 (mg/ml)-1 and to PC/cholesterol (50% w/w) liposomes they are 6.7 +/- 0.9 (mg/ml)-1 and 8.0 +/- 0.8 (mg/ml)-1, respectively. The vertical distribution of the dyes in the bilayer was determined by quenching their fluorescence with spin-labeled stearic acids. PF-II was found to reside deeper in the membrane than HPD. Cholesterol was found to modulate the distribution of the two dyes to a greater extent then DPPC and DMPC. The modulation mechanism is discussed.
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Polymorphonuclear leukocyte (PMNL) infiltration is an important characteristic in psoriatic lesions. Elevated concentrations of the chemoattractant eicosanoid leukotriene B4 (LTB4) are present in psoriatic skin. Its chemotactic activity is mediated via high affinity receptors on PMNL. The goal of our work was to ascertain whether PMNL infiltration in psoriasis can be accounted for by functional abnormalities of the circulating PMNL due to alterations in the LTB4 receptor density or affinity (or both). No significant difference was found between patients with psoriasis, healthy controls and patients with another inflammatory dermatosis (atopic eczema) with regard to the binding parameters of LTB4 receptors on PMNL. Our findings suggest that PMNL accumulation in psoriatic skin may be the result of an excess of cutaneous chemoattractant rather than the increased readiness of psoriatic PMNL to migrate towards LTB4 due to altered LTB4 receptor density or affinity.
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Based on animal experiments with a sutureless anastomosis, the sutureless compression anastomotic technique (AKA) was introduced to colorectal surgery. The procedure was applied to 140 patients following resections of the distal colon and rectum. The outcome was controlled prospectively. Anastomosis fistulae occurred in 8 out of 140 patients (5.7%). Excluding the 16 patients with a primary protective colostomy the leakage rate was 6.4%. Out of 67 patients with an anastomosis height of 10 cm or less, 6 developed fistulae (8.9%). Excluding the 11 patients with primary colostomy the leakage rate was 10.7%. 3 patients showed clinically inapparent fistulae in the routinely performed gastrografin enema. The clinical application of the compression-anastomotic technique revealed no disadvantage. The technique seems to have advantages due to more areactive anastomosis healing.
A review of all autopsy and toxicology reports for persons dying in New York City in an 11-month period found 935 persons dying with cocaine in their bodies. Cocaine-positive fatalities were more likely in the young black and Hispanic and male population. In addition to cocaine and its metabolites, heroin and other opiates were found in 39% of persons and ethanol in 33% and barbiturates and minor tranquilizers in only 2% of the deceased. Cocaine overdose was responsible for 4% of the deaths and overdose with heroin and cocaine for 12% of the deaths. Violence was often the cause of death. Thirty-eight percent died of homicide, seven percent of suicide, and eight percent from accidents. Of particular interest were 6 persons who died of acute cardiac events directly related to cocaine as well as 4 cases of ruptured dissections of the ascending aorta, and 9 cases of cerebral hemorrhage. Autopsy findings for these individuals are described, and possible mechanisms of death are discussed.
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We identified leukotriene B4 (LTB4)/12-hydroxyeicosatetraenoic acid (12-HETE) binding sites in a squamous cell cancer-derived human epidermal cell line. Analysis of the binding data revealed a single class of binding sites with a dissociation constant of 0.16 microM and a Bmax of 3.8 x 10(6) sites per cell. Competitive binding assays with various eicosanoids at 37 degrees C showed nearly equal binding of 12(S)-HETE, 12(R)-HETE and LTB4. 5(S)-HETE and LTB4-analogs bound with lesser affinity. Specific LTB4 binding at 37 degrees C could also be demonstrated in freshly isolated normal human keratinocytes. Since lipoxygenase-derived eicosanoids are thought to play an important role in hyperproliferative and inflammatory skin diseases, the identification of LTB4/12-HETE binding sites in keratinocytes could have implications for the development of new drugs controlling these disease processes.