Matrix metalloproteinase-7 activates heparin-binding epidermal growth factor-like growth factor in cutaneous squamous cell carcinoma.

BACKGROUND: Tumour-specific expression of matrix metalloproteinase (MMP)-7 has been noted in cutaneous squamous cell carcinomas (SCCs) in patients with recessive dystrophic epidermolysis bullosa (RDEB). OBJECTIVES: To examine the potential role of MMP-7 in shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in RDEB-associated and sporadic SCCs. METHODS: Tissue microarrays of RDEB-associated SCC (n = 20), non-EB SCC (n = 60) and Bowen disease (n = 28) were immunostained for MMP-7, CD44 variant 3 (CD44v3) and HB-EGF. Shedding of HB-EGF was studied in vitro using two cutaneous SCC cell lines. RESULTS: Immunohistochemical analysis showed that HB-EGF was absent in tumour cells when MMP-7 and CD44v3 colocalized, and that the absence of HB-EGF was more pronounced in RDEB-associated SCCs than in non-EB SCCs. The loss of HB-EGF in MMP-7-CD44v3 double-positive areas was interpreted to indicate shedding and activation of HB-EGF; this was also detected in Bowen disease indicating its importance in the early phase of SCC development. Specific knockdown of MMP-7 expression in human cutaneous SCC cells by small interfering RNA inhibited shedding of HB-EGF and resulted in diminished activation of the EGF receptor (EGFR) and ERK1/2, and in reduced proliferation of SCC cells. CONCLUSIONS: These findings provide evidence for the role of MMP-7 in promoting the growth of cutaneous SCCs by shedding HB-EGF, and identify EGFR signalling as a potential therapeutic target in RDEB-associated SCC and unresectable sporadic cutaneous SCC.

Transformation-specific matrix metalloproteinases (MMP)-7 and MMP-13 are expressed by tumour cells in epidermolysis bullosa-associated squamous cell carcinomas.

BACKGROUND: Patients with recessive dystrophic epidermolysis bullosa (RDEB) have an increased risk of developing rapidly progressive and metastatic cutaneous squamous cell carcinomas (SCC). It is unclear why these SCC behave more aggressively than sporadic SCC. Matrix metalloproteinases (MMP) are a family of endopeptidases that contribute to growth, invasion and metastasis of SCC. The role of MMP in RDEB-associated SCC is not known. OBJECTIVES: To investigate the expression of MMP-7, MMP-13 and MMP-9 in RDEB-associated SCC in comparison with sporadic SCC and Bowen's disease. METHODS: Immunohistochemical analysis of 25 RDEB-associated SCC, 61 sporadic SCC and 28 sporadic lesions of Bowen's disease was carried out using monoclonal antibodies for MMP-7, MMP-9, MMP-13 and E-cadherin and syndecan-1. RESULTS: MMP-7 was detected in all RDEB-associated SCC, in tumour cells within the invasive edge, where E-cadherin and syndecan-1 were markedly diminished or absent. MMP-7 expression was also observed in 98% of sporadic SCC and in 68% of Bowen's diseases. MMP-7 staining was significantly stronger in RDEB-associated SCC than in sporadic SCC, and was most abundant in poorly differentiated tumours. MMP-13 was detected in tumour cells in 96% of RDEB-associated SCC and in all sporadic cutaneous SCC. MMP-9 was detected in the inflammatory cells in all SCC examined. CONCLUSIONS: These results identify MMP-7 and MMP-13 as tumour cell-specific markers for SCC progression and as potential therapeutic targets in RDEB-associated SCC. The pattern of immunolabelling suggests that MMP-7 may shed E-cadherin and syndecan-1 from the SCC cell surface.

Evaluation of dithiocarbamates and beta-diketones as chelating agents in supercritical fluid extraction of Cd, Pb, and Hg from solid samples.

The use of four dithiocarbamates and three fluorinated beta-diketones as potential chelating agents for three transition metal ions (Cd(2+), Pb(2+), and Hg(2+)) extracted from spiked sand and filter paper samples by supercritical fluid extraction (SFE) was investigated. The extractions were performed at 45 degrees C and 250 atm for spiked sand samples and at 60 degrees C and 200 atm for filter paper samples using supercritical carbon dioxide modified with 5% methanol. At 250 atm and using carbon dioxide modified with 5% methanol, the recoveries of Cd(2+), Pb(2+), and Hg(2+) ions from spiked sand samples were 95% with lithium bis(trifluoroethyl)dithiocarbamate (LiFDDC) as the chelating agent; they ranged from 83-97% with diethylammonium diethyldithiocarbamate and from 87-97% with sodium di-ethyldithiocarbamate as chelating agents, and from 68-96% with trifluoracetylacetone, hexafluoroacetylacetone, and thenoylfluoroacetone as chelating agents. Ammonium pyrrolidinedithiocarbamate was not effective in the chelation SFE of Cd(2+), Pb(2+), and Hg(2+) ions from either spiked sand or spiked filter paper samples under the extraction conditions used. Supercritical carbon dioxide alone gave consistently lower analyte recoveries than supercritical carbon dioxide modified with 5% methanol. The results suggest that the solubility of the metal chelate in the supercritical fluid plays a more important role than the solubility of the chelating agent in the supercritical fluid, as long as sufficient chelating agent is present in the fluid phase. Fluorination of the chelating agent, as in the case of LiFDDC, increases the solubility of the metal chelate, and subsequently enhances the extraction efficiency for the metal ions.

Supercritical fluid extraction of organic and inorganic mercury from solid materials.

Mercuric ions (Hg(2+)) can be extracted from solid samples (cellulose matrix) using methanol modified supercritical CO(2) containing the fluorinated chelating agent lithium bis(trifluoroethyl)dithiocarbamate (LiFDDC). Methylmercuric chloride (CH(3)HgCl) and dimethylmercury [(CH(3))(2)Hg] can be extracted by supercritical CO(2) without chelating agent and modifier. The solubility of Hg(FDDC)(2) in supercritical CO(2) has been determined to be 5 x 10(-3)M at 5O degrees C and 150 atm, which is about 3 orders of magnitude greater than that of the non-fluorinated analogue Hg(DDC)(2). Use of methanol (5%)-modified CO(2) further enhances the solubility of Hg(FDDC)(2) by a factor of 2.4. A small amount of water added to the sample matrix tends to facilitate the extraction of Hg(FDDC)(2) and CH(3)HgCl. Potential applications of this in situ chelation-supercritical fluid extraction method for the preconcentration of mercury species and treatment of mercury contaminated wastes are discussed.

Interlaboratory evaluation of an off-line supercritical fluid extraction/infrared spectrometric method for determination of petroleum hydrocarbons in solid matrixes.

A collaborative study was conducted, with 14 laboratories participating, to determine the method accuracy and precision of the proposed U.S. Environmental Protection Agency Methods 3560 and 8440. These methods involve the extraction of petroleum hydrocarbons from solid matrixes with supercritical carbon dioxide at 340 atm and 80 degrees C for 30 min (dynamic), collection of the extracted materials in tetrachloroethene (Method 3560), and analysis of the extracts by infrared (IR) spectrometry (Method 8440). The study design was based on the AOAC blind replicate design with balanced replicates. The study samples consisted of 4 solid matrixes that had petroleum hydrocarbon contents ranging from 614 to 32,600 mg/kg. Each of the 4 matrixes was extracted in triplicate, and the extracts were analyzed with 2 different IR spectrometers. In addition, each of the participating laboratories extracted a sample of unspiked clay soil, the same clay soil spiked with corn oil and reference oil at 1000 mg/kg each, and the same clay soil wetted to 30% water content and spiked with motor oil at 10,000 mg/kg (the latter 3 samples were extracted only once). Results indicated that the overall method accuracy for concentrations ranging from 614 to 32,600 mg/kg was 82.9%; the mean recoveries of petroleum hydrocarbons for each of the 4 solid matrixes ranged from 77.9 to 107% for analyses performed with the Perkin-Elmer Fourier transform IR spectrometer and from 75.9 to 101% for analyses performed with the Buck-Scientific IR spectrometer; the differences between the 2 instruments on a sample-by-sample basis were less than 17% for the total petroleum hydrocarbon determinations. The interlaboratory method precisions (RSDR) appeared to be matrix-dependent and ranged from 17.3 to 45.4% for analyses performed with the Perkin-Elmer Fourier transform IR spectrometer and from 16.7 to 47.9% for the Buck-Scientific IR spectrometer. The intralaboratory method precisions (RSDr) appeared to be less matrix-dependent and ranged from 11.5 to 17.0% for analyses performed with the Perkin-Elmer FTIR spectrometer and from 11.1 to 18.2% for the Buck-Scientific IR spectrometer. Method accuracy and precision data are also presented for the 5 laboratories that used Isco supercritical fluid extraction systems and for the 7 laboratories that used vessels with volumes of 3.5 mL or less with different supercritical fluid extraction systems.

Cleanup of environmental sample extracts using Florisil solid-phase extraction cartridges.

Disposable cartridges containing 1 g of Florisil are investigated for cleanup of extracts obtained from various environmental matrices. Elution patterns and recoveries are determined for 22 chlorinated hydrocarbons and 16 phthalate esters in the presence of interferents such as corn oil, diesel hydrocarbons, organochlorine pesticides, and chlorinated phenols. Hexane, hexane/diethyl ether (1:1), hexane/acetone (9:1), and various combinations of hexane/methylene chloride are used as eluants.

Evaluation of a high-resolution gas chromatography/high-resolution mass spectrometry method for the determination of 2,3,7,8-tetrachlorodibenzo-p-dioxin in soil and water.

An analytical protocol for the determination of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and total TCDDs in soil, sediment, and aqueous samples using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS) was evaluated through replicate analyses of fortified and unspiked soil and aqueous samples. The results of these analyses demonstrated that the method is useful for the determination of 2,3,7,8-TCDD and total TCDDs at concentrations ranging from 10 to 200 pg/g (ppt) in soil samples and from 100 to 2000 pg/l (ppq) in aqueous samples. Absolute recoveries of the method internal standard, (13C12-2,3,7,8-TCDD, ranged from 24 to 88%. Lower levels of detection can be achieved through a slight modification of the method with respect to initial sample size and/or final extract volume. Instrumental parameters that affect data quality, specifically HRGC column performance, mass resolution and mass measurement accuracy are presented.

Single-laboratory evaluation of EPA method 8080 for determination of chlorinated pesticides and polychlorinated biphenyls in hazardous wastes.

Method 8080, as published in the Second Edition of "Test Methods for Evaluating Solid Waste," EPA Manual SW-846, has been evaluated in a single-laboratory study. The Florisil procedure recommended in Method 8080 for sample cleanup does not separate organochlorine pesticides (OCPs) from the polychlorinated biphenyls (PCBs). Consequently, gas chromatographic analysis of OCPs on the packed column recommended in the method may result in false identifications or in no identifications at all when PCBs are present. Therefore, silica gel was substituted for Florisil, a capillary column was substituted for the packed column, and a sulfur cleanup procedure was incorporated in the method. The revised method was evaluated with samples spiked at 3 concentrations. Precision and accuracy indicate that the revised method can be reliably applied to the determination of OCPs and PCBs in liquid and solid matrixes. Detection limits for liquid matrixes range from 0.02 to 0.09 micrograms/L for OCPs and from 0.5 to 0.9 micrograms/L for PCBs. Detection limits for solid matrixes range from 1 to 6 micrograms/kg for OCPs and from 60 to 70 micrograms/kg for PCBs.

[Cholestasis and liver cell necrosis resulting from acute pulmonary embolism (author's transl)]. / Cholestase und Parenchymnekrosen der Leber bei akutem Cor pulmonale infolge Lungenembolie.l

124 autopsy cases with acute pulmonary embolism were investigated. Severe or moderate necrosis of parenchymal cells were found in 24%, and disseminating microfocal necrosis furthermore in 32%. An unsignificant or mild cholestasis was observed in 44%. The cause of necrotic liver damage is a complex circulatory disturbance, formed by acinar liver structure. A correlation between degree of thromboembolism and liver necrosis or cholestasis does not exist.

[Appendectomy in parallel with gynaecological laparotomy (author's transl)]. / Simultanappendektomie bei gynäkologischer Laparotomie.

An account is given in this paper of 102 cases of appendectomy in parellel with 193 gynaecological laparotomies (52.9 per cent), with reference being made to the small amount of associated complication, as borne out by literature data on larger groups of patients. Particular reference is made, in that context, to legal and clinical prerequisites and to counter-indictions. The authors' own pathohistological findings differed from figures around 90 per cent, as reported elsewhere, in that more or less conspicuous tissue peculiarities were recorded from only 37.5 per cent of all simultaneously removed appendices. That discrepancy in evaluation is discussed. With the relative increase in incidence and complication of senile appendicitis in mind, appendectomy in parallel with gynaecological laparotomy is recommended as a genuine prophylaxis, yet, with due consideration of all necessary conditions.

[Morphological studies on the problem of cholestasis due to cardiac insufficiency and its relationship to parenchymal necroses of the liver]. / Morphologische Untersuchungen zum Problem der kardial bedingten Cholestase und ihrer Beziehungen zu Parenchymnekrosen der Leber.

For the differentiation of the disturbances of the uric acid metabolism the determination of the uric acid clearance is a valuable help. A normal clearance (greater than or equal to 0.116 ml/s, 7 ml/min) in hyperuricaemia speaks for an overproduction of uric acid (type I), a decreased clearance (less than or equal to 0.100 ml/min) speaks for a disturbance of the renal excretion (type II). By additional parameters which are simply to be got further subtypes (Ia, Ib, IIa, IIb, III) can be delimited. All examinations can be performed under ambulatory conditions. On the basis of this division the antihyperuricaemics may be better used. The application of the drugs according to types favours the decrease of the side-effects of the drugs and additionally shows economic advantages.

[Small myomas of stomach in autopsy cases (author's transl)]. / Miniaturmyome des Magens im Sektionsgut.

In a series of 800 unselected autopsy cases in 46 patients gastric myomas were founded. These tumors are the most common non-epithelial neoplasms of gastric wall. The average age runs to 77 years. Myomas are mainly localized in the fundus and corpus of the stomach. They originate from the internal layer of the muscularis propria. These myomas grow very slowly, and calcification or sclerosis are frequent. The practical clinical importance is insignificant.

[Sudden cardiac death due to myocardial sarcoidosis]. / Plötzlicher Herztod infolge Myokardsarkoidose.

The participation of the myocardium in sarcoidosis is a severe complication which in very rare cases may lead to the acute cardiac death. Morphological problems result from all accessory cardiac changes.

[Possibilities and limitations of aspiration curettage]. / Moznosti a hranice aspiracní kyretáze.

PIP: Since aspiration curettage is increasingly common, we undertook a study aimed at comparing the histological suitability of samples acquired by this method to conventional curettage methods. Both types of curettage were performed on 123 women aged 23-76. Before undergoing aspiration curettage, women received 50 mg. Pethidine and .01 mg. Atropine/kg. body weight. Anesthetics for conventional curettage were hexabarbitol and nitrous oxide. Histological reports on samples acquired by both methods of curettage were identical in ale 15 cases of breakthrough bleeding, in all 6 patients with hypermenorrhea, in both patients on whom the procedure was done for diagnostic purposes, and in 18 of 21 cases of long-term bleeding. 47 of 63 women with post-menopausal bleeding had identical findings in both samples; 9 of these women had significant findings in the conventionally obtained sample only and 7 in the aspirated sample only. Of 16 cases of cervical polyps detected in the conventional curettage samples, only 3 were simultaneously discovered in the aspirated samples. 5 cases of uterine cancer were simultaneously detected in both samples. Aspiration curettage dectected cervical cancer in one case where conventional caurettage did not, but one case of cervical cancer in conjunction with polyps was not detected by aspiration curettage. Thus, except in cases where cervical polyps are suspected the diagnostic and therapeutic utility of aspiration curettage is high. An advantage of aspiration curettage is that it need not be done under general anesthesia and may be done on an out-patient basis. This reduces surgical risks to the patient and promotes the efficient utilization of hospital facilities.^ieng

[Bronchial carcinoma in multiple bilateral amyloid tumors of the lung]. / Bronchialkarzinom bei multiplen bilateralen Amyloidtumoren der Lunge.

It is reported on an up to now not described combination of bronchial carcinoma and multiple amyloid tumours of the lung as autopic side findings in a 68-year-old patient.