Uptake of Adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas

Summary Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0,9 and 4,6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient.In anin vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.     

Mechanics of the anterior drawer and talar tilt tests: A cadaveric study of lateral ligament injuries of the ankle

We analyzed the changes in lateral ligament forces during anterior drawer and talar tilt testing and examined ankle joint motion during testing, following an isolated lesion of the anterior talofibular ligament (ATFL) or a combined lesion of the ATFL and calcaneofibular ligament (CFL). 8 cadaver specimens were held in a specially designed testing apparatus in which the ankle position (dorsiflexion-plantarflexion and supination-pronation) could be varied in a controlled manner. Ligament forces were measured with buckle transducers, and joint motion was measured with an instrumented spatial linkage. An anterior drawer test was performed using an 80 N anterior translating force, and a talar tilt test was performed using a 5.7 Nm supination torque with intact ligaments, after sectioning of the ATFL, and again after sectioning of the CFL. The tests were repeated at 10° dorsiflexion, neutral, and 10° and 20° plantarflexion. In the intact ankle, the largest increases in ATFL force were observed during testing in plantarflexion, whereas the largest increases in CFL force were observed in dorsiflexion. Isolated ATFL injury caused only small laxity changes, but a pronounced increase in laxity was observed after a combined CFL and ATFL injury.     

Monoclonal antibodies to intermediate filament proteins: Diagnostic specificity in orbital pathology

Intermediate filaments derived from different cell types are antigenically distinct. Monoclonal antibodies to human intermediate filament proteins can, therefore, be used as tissue-specific reagents capable of distinguishing cell type in poorly differentiated neoplasms. We report a case demonstrating the specificity of antiintermediate filament protein antibodies in establishing a difficult orbital diagnosis of esthesioneuroblastoma.     

A gene for autosomal recessive limb-girdle muscular dystrophy maps to chromosome 2p

The limb-girdle muscular dystrophies are a clinically and geneticallyheterogeneous group of disorders. We have ostudied two largeinbred families of different ethnic origin and excluded linkageto LGMD2 on chromosome 15q and SCARMD on chromosome 13. Proceedingto a genomic linkage search, we have now identified linkageto markers D2S134 and D2S136 on chromosome 2p (maximum lod score3.57 at zero recombination). The phenotype in the two familieswas similar, with onset in the pelvic girdle musculature inthe late teens and usually relatively slow progression. Thiswork Identifies a second locus for autosomal recessive limb-girdlemuscular dystrophy.     

Treatment with an anti-CD18 monoclonal antibody in rabbits inhibits pneumococcal-induced leukocyte recruitment in the skin,but not in the meninges

Inflammatory recruitment of leukocytes into the cerebrospinal fluid (CSF) during bacterial meningitis has been shown to contribute to the neurological damage commonly associated with this disease. In this study we tested whether inhibition of firm leukocyte adhesion to vascular endothelium could reduce leukocyte recruitment into the subarachnoid space (SAS) and into the skin in rabbits challenged with pneumococcal cell wall (PCW) antigen. PCW was given either as an intracisternal or an intradermal (i.d.) injection. Intravenous (i.v.) treatment with a monoclonal antibody (mAb), IB4, against the leukocytic adhesion molecule CD18 has previously been documented to attenuate leukocyte CSF accumulation in experimental bacterial meningitis. In the present study, i.v. treatment with anti-CD18 mAbs (IB4) only tended to inhibit CSF leukocyte influx in animals with PCW-induced meningitis. However, if the antigen was injected i.d., treatment i.v. with the same mAb (IB4) dramatically reduced leukocyte accumulation in the skin. Our findings indicate that the mechanisms responsible for PCW-induced inflammatory accumulation of leukocytes in skin and meninges are different.     

Molecular characterisation of two mumps virus genotypes circulating during an epidemic in Lithuania from 1998 to 2000

Summary.  An epidemic of mumps in Lithuania started in December 1998 and continued until May 2000. The total registered number of cases was about 11.000 of a total of 3,7 million inhabitants in Lithuania (29,7 cases/10000). Virus- containing samples were collected from 80 patients treated at the hospital of Kaunas from October 1999 until the end of the epidemic. Out of the 80 patients with parotitis, meningitis was observed in 11 patients and orchitis in 22 of 69 male patients. Twenty-seven virus strains were genotyped by nucleotide sequencing of the small hydrophobic (SH) protein gene, and the 57 amino acid sequences of the gene were deduced. Twenty-five virus strains belonged to the C genotype and two were of the D genotype. By phylogenetic analysis the virus strains causing meningitis grouped in a separate cluster, designated C1, within the C genotype. Another group of ten of the 25 genotype C strains exhibited an amino acid triplet at amino acid positions 28 to 30 of the protein, consisting of valine, alanine and serine, instead of the previously recognised valine, valine and serine combination of genotype C. The amino acid alanine at position 29 was found in combination with the amino acid serine at position 48. This variant was designated C2 and it was associated with parotitis. The amino acid alanine at position 29 and serine in position 48 of the C2 genotype may constitute a marker of low neurovirulence compared to other genotype C strains. Received July 9, 2001 Accepted October 23, 2001     

Production and characterization of monoclonal antibodies directed against Bordetella pertussis lipopolysaccharide.

Hybrid cell lines producing monoclonal antibodies against Bordetella pertussis lipopolysaccharide (LPS) were established. The specificity of the antibodies was ascertained by enzyme-linked immunosorbent assay (ELISA) and ELISA-inhibition experiments with LPS and delipidated polysaccharide fragments (PS-1 and PS-2) prepared from B. pertussis LPS. Monoclonal antibody 9-1-H5 reacted with B. pertussis LPS only, whereas monoclonal antibodies 6-4-H6 and 9-2-A8 reacted with PS-1 and PS-2 as well as B. pertussis LPS. The antibodies did not react with LPS prepared from B. parapertussis and B. bronchiseptica in an LPS-specific ELISA. A monoclonal antibody-based sandwich ELISA was developed for detection of B. pertussis LPS. This assay had a detection limit of B. pertussis LPS in concentrations ranging from 0.16 to 0.32 microgram/ml. The assay was also shown to be specific for the detection of whole B. pertussis bacteria. No cross-reactions were observed with strains of Branhamella catarrhalis, Neisseria meningitidis, Streptococcus miteor, Haemophilus influenzae, or Legionella pneumophila. The monoclonal antibodies might be useful for the detection of soluble antigens and whole bacteria in clinical samples and for studies of the immunochemical structure of B. pertussis LPS.     

Qualitative assessment and morphometry in the study of the ileal reservoir after restorative proctocolectomy

Little is known about the long-term effects on the reservoir mucosa in patients with ulcerative colitis and familial polyposis coli who undergo proctocolectomy with subsequent construction of ileal reservoir/pouch and ileoanal anastomosis. In these patients, questions regarding adaptation towards a more colon-like mucosa and/or development of (pre)malignant changes are of particular importance. With the aim of designing a method for reliable evaluation of the mucosa in the ileal pouch, biopsies from 10 patients were studied by semiquantitative assessment and morphometry. The findings were compared with those obtained from normal jejunum, ileum, and colon. The following parameters were found to be important: Villous surface density, quantity of goblet cells, number of mitoses, and the presence/absence of predominantly sulphated mucin+ goblet cells. The number of Paneth cells did not show significant changes. The villous surface density was determined by a cycloid test system applied to vertical sections. Semiquantitative assessment was a sufficiently precise method for the evaluation of the quantity of goblet cells. The counting of sulphated mucin+ goblet cells was not reproducible, instead a simple statement about the presence or absence of these cells was judged to be adequate. The number of mitoses and of Paneth cells were counted directly. During the first year of function the ileal pouch showed signs of adaptation towards a colon-like mucosa: Reduction of villous surface density, increased mitotic activity, and appearance of sulphated mucin+ goblet cells. The number of Paneth cells did not show significant changes. The amount of goblet cells was generally not increased, rather reduced in some patients.