Intrinsic resistance to anticancer agents in the murine pancreatic adenocarcinoma PANC02

Summary PANC02 is a ductal adenocarcinoma of the pancreas that is resistant to every known class of clinically active antitumor agent. To study the mechanism(s) underlying the intrinsic drug resistance of this tumor, a mammary adenocarcinoma (CA-755) that also grows in C57/BL mice and is known to be drugsensitive was used for comparison. PANC02 resistance and CA-755 sensitivity to several antitumor agents and to X-ray therapy was confirmed in mice, and PANC02 also demonstrated relative resistance in tissue culture. Relative to Chinese hamster ovary (CHO) and CA-755 cells, PANC02 did not appear to show a higher rate of mutation to drug resistance in culture as based on the 6-thioguanine resistance marker. Although P-glycoprotein characteristic of the multidrug resistance (MDR) phenomenon could be demonstrated at the mRNA level using a sensitive RNAse protection assay, the level of expression found was several orders of magnitude lower than that observed in phenotypic MDR cell lines. Furthermore, quinidine failed to increase the sensitivity of PANC02 cells to Adriamycin under conditions that clearly potentiated the toxicity of the drug to a CHO cell line exhibiting classic MDR traits. The heterogeneity in the distribution of drugs was inferred as being significantly greater in PANC02 versus CA-755 cells in vivo as based on measurements of within-animal, within-tumor variance in the distribution of the marker compounds inulin and antipyrine. Although it may not be the only mechanism involved, this greater intratumor heterogeneity in drug distribution could theoretically play a major role in the intrinsic drug resistance of PANC02 in vivo.Supported by grant CH-458 from the American Cancer Society, by grant CA-28034 from the National Cancer Institute, and in part by Cancer Center Core Support grant, NIH-NCI-CA-16672. Animals were maintained in facilities approved by the American Association for Accreditation of Laboratory Animal Care and in accordance with current United States Department of Agriculture, Department of Health and Human Services, and National Institutes of Health regulations and standards     

Virulent human strains of group G streptococci express a C5a peptidase enzyme similar to that produced by group A streptococci.

Specific proteolytic destruction of the human chemotaxin, C5a, is a property of group A and B streptococcal pathogens. Here we show that virulent group G streptococci from human sources also express C5a peptidase activity. The enzyme responsible for this activity is approximately the same size as and is antigenically similar to that produced by group A streptococci. On the basis of Southern hybridization analysis with an internal fragment of the group A C5a peptidase gene (scpA) as a probe, a copy of this gene was found in the genome of all group G human isolates tested. Comparison of partial restriction maps of scpA and scpG revealed significant similarity between the two genes. Group G strains isolated from dogs and cows were found to lack C5a peptidase activity and did not hybridize to the scpA-specific probe. The association of this activity with three streptococcal species suggests that elimination of phagocyte chemotactic attractants is a more universal virulence mechanism than originally anticipated.     

Antenatal Screening for HPA-la by Flow Cytometry

Summary: regnant women who attended antenatal clinics at King George V Hospital, the Birth Centre or were referred by obstetricians from February to July. 1996 were screened for the platelet antigen HPA-la by flow cytometry. Forty out of 2300 (1.7%) were found to be negative for this antigen . Of the 28 women followed throughout their pregnancy, none developed antibody to HPA-la. Platelet counts performed on samples from 17 babies born to 17 of these mothers were all normal. This study proves the simplicity and rapidity of flow cytometry for platelet antigen screening. The results were comparable with the Solid Phase Red Cell Adherence (SPRCA) method and with PCR. The lack of a plentiful supply of specific antibody and the rarity of fetomaternai alloimmune thrombocytopenia (FMAIT) argue against the introduction of routine screening for maternal HPA-la status at the present time.     

Use of an indigenous fish species, Fundulus zebrinus, in a mosquito abatement program: a field comparison with the mosquitofish, Gambusia affinis.

Studies were conducted relating mosquito production in small ponds to presence or absence of larvivorous fishes. Data collected showed that native killifish and introduced mosquitofish controlled mosquito larvae at the same level and support the use of indigenous fish species in mosquito abatement programs.     

Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

A comparison of motor unit behaviour in young and aged subjects

We evaluated motor unit behaviour in young and aged subjects during ramped tension development and release to 10% maximum voluntary contraction requiring 10 seconds to complete. Six young and six elderly adults performed isometric abductor digiti minimi muscle contractions while motor units were recorded with implanted fine wire electrodes. Computer interactive programs yielded interspike interval (ISI) data for 16 units from the young and for 15 units from the aged subjects. Mean ISIs for young were 88.4 ms for shortening and 96.5 ms for lengthening contractions. Units from the aged had ISIs of 110.5 ms and 117.1 ms for shortening and lengthening contractions. Some evidence for between-group differences in firing pattern during ascending and descending ramps was also found.     

An experience of renal replacement therapy in a combined neonatal and paediatric intensive care unit of Hong Kong

Intensive care services are expensive. The experience of developing a combined paediatric and neonatal intensive care unit (ICU) in a regional hospital is reported with reference to the provision of renal support for the critically ill patients. The combined unit is staffed by a team of paediatric intensivists, each of whom has special interest in a subspecialty, including cardiology, respiratory medicine, nephrology and neonatology. In the past 7 years, renal replacement therapy (peritoneal dialysis and haemofiltration) was provided to 40 patients, with comparable mortality and complication rates to other reports. This arrangement has been feasible and might be more efficient than running separate paediatric and neonatal ICUs or combining the paediatric ICU with the adult ICU.