Entrapping homogeneous catalysts by sol-gel methods: the bottom-up synthesis of catalysts that recycle and cascade.

Homogeneous catalysts entrapped in silica matrices, including ionic liquid containing 'ionogels', exhibit high selectivity, unexpected activity and excellent recyclability.

Clinical heterogeneity in recessive epidermolysis bullosa due to mutations in the keratin 14 gene, KRT14.

BACKGROUND: Epidermolysis bullosa simplex (EBS), the most common subtype of EB, is usually inherited as an autosomal dominant trait caused by mutations in either the keratin 5 (KRT5) or keratin 14 (KRT14) genes. Recessive EBS (R-EBS) is extremely rare. METHODS: We present the first Australian patient diagnosed with R-EBS, to our knowledge, and a comprehensive review of genotypes and phenotypes of R-EBS reported cases. RESULTS: The female proband, of Turkish descent with consanguineous parentage, was referred to us at the age of 8 years. Clinically, she had a severe phenotype including generalized blisters, mucosal involvement and EB naevi. Immunofluorescence mapping and electron microscopy were consistent with a diagnosis of EBS. Staining for Keratin 14 (K14) was negative. The basal layer, however, reacted with monoclonal antibodies to keratins 6 (K6) and 16 (K16). Mutation screening from genomic DNA showed that the proband was homozygous for the truncation mutation Y204X in exon 3 of KRT14, and both unaffected parents were heterozygous for a single KRT14 Y204X mutation. The phenotype of our patient is reported in more detail and with longer follow-up than those of others published in the literature. DISCUSSION: The proband's phenotype was severe as an infant but improved with age, suggesting that an alternative keratin is pairing with K5 in her skin to compensate for the loss of K14--a novel biological compensatory mechanism. It is interesting that K6 and K16 were expressed, as these are normally positive in hyperproliferative skin disorders.

A new source of hepatocytes for transplantation.

INTRODUCTION: The most effective treatment for acute or chronic liver failure is orthotopic liver transplantation. Worldwide there is a shortage of organs for transplantation. This shortage has called for research into new treatments for management of patients with liver failure. One such treatment is hepatocyte transplantation. During liver resections considerable amounts of normal liver are unavoidably resected. We aim to harvest these hepatocytes and to filter the tumor cells from them to provide a source for transplantation. MATERIALS AND METHODS: After liver resection, the largest vessel at the resected liver edge was identified and cannulated. Seglen's two-stage technique of perfusing the liver with EDTA and collagenase was performed to harvest the hepatocytes. Ep-CAM Ags are consistently present on the surface of epithelial cells and in particular in colorectal cancer cells. Therefore, MOC31 antibodies (selective Abs for Ep-CAM) attached to magnetic beads were used to target the tumor cells. These tumor cells are selectively removed using a magnet. CEA staining was then used to ensure the hepatocyte collection was tumor cell free. Five million hepatocytes were rosetted with one million HT29 CRC cells to assess the immunomagnetic filtration technique. RESULTS: The hepatocyte harvesting resulted in 864,000 viable hepatocytes to be harvested per gram of liver. Histochemical staining using CEA demonstrated 75% of the HT29 cells in the hepatocyte collection were removed after one use of magnetic beads. CONCLUSION: We have demonstrated the successful initial stages of harvesting tumor-free hepatocytes from liver resected for malignancy.

ATM induction insufficiency in a radiosensitive breast-cancer patient.

The ataxia telangiectasia (A-T) gene (ATM) is a dominant breast cancer gene with tumour suppressor activity. ATM also regulates cellular sensitivity to ionising radiation (IR) presumably through its role as a facilitator of DNA repair. In normal cells and tissues the ATM protein is rapidly induced by IR to threshold/maximum levels. The kinase function of the ATM protein is also rapidly activated in response to IR. The fact that women carriers of ATM mutations can have an increased risk of developing breast cancer and that many sporadic breast tumours have reduced levels of the ATM protein broadens the scope of ATM's tumour suppressor within the breast. This report describes the downregulation of ATM protein levels in a radiosensitive breast cancer patient. Postinduction ATM levels were up to tenfold lower in the patient's fresh tissues compared to normal controls. These results might indicate a much broader role for ATM anomalies in breast cancer aetiology.

Histamine, mast cells and tumour cell proliferation in breast cancer: does preoperative cimetidine administration have an effect?

Endogenous histamine has been shown to effect growth mechanisms in experimental mammary carcinomas via H2 membrane receptors (Cricco et al, 1994). Both H1 and H2 binding sites are present in human mammary glands but only 75% malignant carcinomas express H2 receptors (Lemos et al, 1995). The presence of mast cells around tumour tissue raises questions concerning the source of histamine in breast tumour tissue. While cimetidine, an H2 antagonist, has been shown to influence the presence of tumour infiltrating lymphocytes (TIL) in colorectal cancer (Adams and Morris, 1994, 1997) that was not found to be the case in breast cancer (Ng et al, 1995). In recent studies tumour cell proliferation, as measured by Ki-67 antibody labelling, has been seen as an additional prognostic indicator in breast cancer (Railo et al, 1993, 1997; Ferno, 1998; Schauer et al, 1998). We investigated the possibility that cimetidine may influence tumour proliferation by blocking the growth-promoting effects of histamine. No relationship between preoperative cimetidine administration and tumour cell proliferation was seen overall. A weak correlation was seen between tissue histamine content and mast cell count which was not influenced by cimetidine. Tumour cell proliferation correlated well with other prognostic indicators such as grade and differentiation.

Malignant phyllodes tumours of the breast display increased stromal p53 protein expression.

AIMS: To determine the variation in p53 protein expression in phyllodes tumours and fibroadenomas of the breast. METHODS AND RESULTS: Fifteen phyllodes tumours (six malignant, nine benign) and 20 fibroadenomas were examined for p53 expression by immunohistochemistry. Five of the six malignant phyllodes tumours showed moderate or strong p53 positivity at sites of peri-epithelial stromal condensation and atypia. All 20 fibroadenomas, nine benign phyllodes tumours and one malignant phyllodes tumour showed either negativity or focal weak nuclear positivity of scattered stromal cells. CONCLUSIONS: Increased p53 immunoreactivity is present in malignant phyllodes tumours in contrast to benign phyllodes tumours and fibroadenomas. Malignant phyllodes tumours display a distinctive pattern of p53 immunostaining which may be of diagnostic value. These findings suggest that p53 protein may be important in the progression of benign to malignant phyllodes tumours.

ATM protein synthesis patterns in sporadic breast cancer.

AIMS: The gene mutated in ataxia-telangiectasia (A-T), designated ATM (for "A-T mutated"), is believed to be associated with an increased risk of developing breast cancer. Most patients with A-T have null mutations of the ATM gene that appear to give rise to a truncated nonfunctional ATM protein. Therefore, the increased risk of breast cancer reported in A-T heterozygotes appears to be the result of haplo-insufficiency of ATM in breast tissues. This study aimed to determine whether reduced synthesis of ATM was also an important factor in sporadic breast cancer. METHODS: Paraffin wax embedded tissues from patients with breast invasive ductal carcinoma (IDC) (n = 42), patients with ductal carcinoma in situ (DCIS) (n = 17), and others with lymph node metastases (n = 14) were studied. A streptavidin-biotin-peroxidase system was used to stain tissue sections for the ATM protein using the ATM-4BA and CT-1 polyclonal and monoclonal antibodies, respectively. The protein truncation test was used to screen for mutations in the ATM gene in those patients who had greatly reduced ATM protein immunoreactivity in the primary carcinoma (n = 3). RESULTS: Most metastatic breast carcinomas in lymph nodes (71%) had greatly reduced or absent ATM protein synthesis, which was significant when compared with that observed in non-metastatic invasive breast carcinomas (p = 0.029; chi 2 test). Although not significant (p = 0.045; chi 2 test), some sporadic breast carcinomas (14 of 42) also had reduced or absent ATM protein immunoreactivity. The protein truncation test did not reveal any gross ATM gene abnormality in the cases tested, indicating that the patients were not A-T heterozygotes, who are predisposed to breast cancer. CONCLUSIONS: A reduction in immunohistochemically detectable ATM protein in sporadic breast carcinoma implicates ATM in the progression of the disease.

Nm23 gene expression in gastric carcinoma: an immunohistochemical study.

BACKGROUND: The gene Nm23 is thought to play a role in the suppression of tumour metastasis. Reduced expression of Nm23 is seen in a number of human cancers, and is associated with increased metastasis and reduced survival, most strongly in ductal breast and colorectal carcinomas. METHODS: Nm23 gene expression was compared in gastric carcinoma and normal gastric mucosa. Twenty-three gastric carcinomas were graded for differentiation as either well, moderately or poorly differentiated. Metastatic deposits from seven of the cases were also examined, along with 10 samples of normal gastric mucosa. Specimens were incubated with a murine monoclonal antibody against the protein product of Nm23, and examined by immunohistochemical staining. A semiquantitative immunostaining index was used. RESULTS: All normal mucosa showed moderate to strong staining; 8 of 15 poorly differentiated carcinomas showed absent or weak staining; 1 of 6 moderately differentiated carcinomas stained weakly. Both well-differentiated carcinomas stained strongly; 1 of 7 metastatic deposits stained weakly. The difference in Nm23 expression between normal mucosa and carcinomas was statistically significant (P=0.024). However, there was no statistically significant difference between the three grades of carcinomas (P=0.51), or between primary and metastatic tumour (P=0.25, all by Chi-squared test). CONCLUSIONS: These results suggest that Nm23 may have a role in gastric carcinoma pathogenesis, but do not show a correlation with metastasis. A larger study, involving detailed clinical staging and follow-up, may be of benefit.

Nursing Information and Data Set Evaluation Center.

The American Nurses Association (ANA) has established the Nursing Information and Data Set Evaluation Center (NIDSEC). The purpose of this Center is to develop and disseminate standards pertaining to information systems that support the documentation of nursing practice, and to evaluate voluntarily submitted information systems against these standards. The target audience for these standards includes both consumers and vendors of clinical information systems. The need for an evaluation center arises out of a long history of calls for standards pertaining to nursing data and to information systems. These calls have come from the Secretary of Health and Human Services Commission on Nursing, the National Commission on Nursing Implementation Project (NICNIP). Standards will be developed to evaluate the completeness, accuracy and appropriateness of four dimensions of nursing data sets and the systems that contain them: 1) Nomenclature; 2) Clinical Content; 3) Clinical Data Repository; and 4) General System Characteristics.

Maintaining patient confidentiality in an electronic world.

The importance of patient confidentiality must be integral to the culture of any healthcare organization. This has always been a part of the professional code of ethics but is being made more difficult with the advances in computerized communication systems. Moving from verbal reports to paper charts to electronic data interchange challenges our current policies and procedures for protecting patient data. The character of access has changed making transportation of confidential data to unknown persons and/or locations often impossible to monitor.

Bedside terminals and quality of nursing documentation.

In this article, the authors report on part one of a three-part investigation studying the impact of bedside terminals at New York University Medical Center, New York, NY. Using a before-after parallel control-group design, the quality of computerized nursing documentation was studied before and after adding computers to patient rooms. The quality of documentation was defined by timeliness and completeness of data. The study hypothesis, which predicted a positive relationship between the presence of bedside terminals and the quality of nursing documentation, was not supported. Study results showed a minimal use of the computer terminals located in patient rooms. A surprising result was the use of terminals located in rooms other than that of the patient for which documentation was made.