Second-Order Effects of Chemotherapy Pharmacodynamics and Pharmacokinetics on Tumor Regression and Cachexia.

Drug dose response curves are ubiquitous in cancer biology, but these curves are often used to measure differential response in first-order effects: the effectiveness of increasing the cumulative dose delivered. In contrast, second-order effects (the variance of drug dose) are often ignored. Knowledge of second-order effects may improve the design of chemotherapy scheduling protocols, leading to improvements in tumor response without changing the total dose delivered.

Partial hypoxanthine-guanine phosphoribosyl transferase deficiency without elevated urinary hypoxanthine excretion.

Partial hypoxanthine-guanine phosphoribosyl transferase (HGPRT) deficiency, also known as the Kelley-Seegmiller syndrome, can give rise to a wide range of neurological symptoms, and renal insufficiency. Biochemically, it is characterized by high uric acid concentrations in blood, high uric acid and hypoxanthine excretion in urine, and decreased activity of hypoxanthine-guanine phosphoribosyl transferase activity (HGPRT). However, normal uric acid concentrations in blood and uric acid excretions in urine have been reported.

Renal function in tyrosinaemia type I after liver transplantation: a long-term follow-up.

Hereditary tyrosinaemia type I is an autosomal recessive inborn error of tyrosine catabolism caused by a deficiency of the enzyme fumarylacetoacetase that results in liver failure, hepatocellular carcinoma, renal tubular dysfunction and acute intermittent porphyria. When treated with liver transplantation, tyrosinaemia type I was considered to be cured. Some years after the first liver transplantations in these patients, some reports focused on the renal function after transplantation.

Altered activity of plasma hemopexin in patients with minimal change disease in relapse.

Since an active isoform of plasma hemopexin (Hx) has been proposed to be a potential effector molecule in minimal change disease (MCD), we tested plasma and urine samples from subjects with MCD in relapse (n = 18) or in remission (n = 23) (after treatment with prednisolone) for presence or activity of Hx. For comparison, plasma or urine from proteinuric subjects with focal and segmental glomerulosclerosis (FSGS, n = 11), membranoproliferative glomerulonephritis (MPGN, n = 9), IgA nephropathy (n = 5) or healthy control donors (n = 10), were incorporated into the study. Electrophoresis and Western blotting methods were used for evaluation of the Hx status, whereas protease activity of Hx was tested upon kidney tissue in vitro according to standard methods.

Expression of Epstein-Barr virus BMRF-2 and BDLF-3 genes in hairy leukoplakia.

The high level of Epstein-Barr virus (EBV) replication found in hairy leukoplakia (HL) provides a unique opportunity to study EBV expression in the oral epithelium. Screening of a cDNA library from an HL biopsy revealed expression of two genes not previously described in vivo: BMRF-2 and BDLF-3. Sequence analysis of the cDNAs demonstrated several nucleotide changes from the B95-8 sequence.

Epstein-Barr virus BMRF-2 and BDLF-3 expression in hairy leukoplakia.

Hairy leukoplakia (HL) is a lesion found on the side of the tongue of immunocompromised individuals, including those with human immunodeficiency virus (HIV) infection. The lesion has unique histopathologic features and is characterised by high-level Epstein-Barr virus (EBV) replication, multiple EBV strains, and extensive inter- and intra-strain recombination. Expression of EBV genes spanning the entire viral life cycle from latency-associated genes to late, replicative genes has been detected in the lesion.

Multicenter study of strains of respiratory syncytial virus.

Two major groups of respiratory syncytial virus (RSV) strains, A and B, have been identified and their patterns of isolation determined in different communities but not simultaneously in multiple communities. In this study, we tested 483 RSV isolates from 14 university laboratories in the United States and Canada for the 1984/1985 and 1985/1986 RSV seasons; 303 (63%) isolates were group A, 114 (24%) were group B, and 66 (14%) could not be grouped. Isolates were subdivided into six subgroups within group A and three within group B; up to six and often four or more different subgroups were isolated in the same laboratory during the same RSV season.

The clinical significance of HTLV-I and HTLV-II infection in the AIDS epidemic.

Although early reports of an etiological role of HTLV-I in AIDS are not supported by subsequent epidemiologic and biologic data, all AIDS specialists should be aware of the possible infection of AIDS risk group members with the HTLV viruses. In the United States, HTLV-II and HIV co-exist in high prevalence among IVDU, and coinfected IVDU may progress more quickly to AIDS. The health effects of solitary HTLV-II infection are currently unknown.

Serological confirmation of human T-lymphotropic virus type I infection in healthy blood and plasma donors.

We wished to develop criteria for serological confirmation of human T-lymphotropic virus type I (HTLV-I) infection in healthy donors. Selected serum or plasma samples reactive by HTLV-I enzyme immunosorbent assay or gel-agglutination assays with at least one viral-specific band on Western immunoblot (WIB) were tested in six laboratories by four WIBs and four radioimmunoprecipitation assays (RIPAs) for antibodies to HTLV-I proteins encoded by gag (p19 and p24), env (gp46 and/or gp61), and tax (p40x) genes. One hundred forty-two donor sera were obtained from 38 Japanese, 69 American, and 35 Caribbean blood or plasma donors.

Prevalence of respiratory syncytial virus subgroups over six consecutive outbreaks: 1981-1987.

Indirect immunofluorescence with strain-specific monoclonal antibodies was used to determine the phenotype of respiratory syncytial virus (RSV) isolates obtained from infants hospitalized in greater Boston over six successive outbreaks from 1981 to 1987. Of 981 isolates, 591 (60%) were classified as subgroup A and 383 (39%) as subgroup B. The prevalence of subgroups varied both between and within yearly outbreaks.

The association of rhinoviruses with lower respiratory tract disease in hospitalized patients.

An analysis of 32 hospitalized infants and children from whom rhinoviruses were isolated in our diagnostic laboratories in 1982-83 suggests that these agents are associated with lower respiratory tract disease with focal findings in susceptible patients. In 23 cases, an acute lower respiratory disease was the cause for admission, while nine patients were cultured after new respiratory symptoms developed during hospitalization. Presenting signs and symptoms included cough (23), fever (19), rhinorrhea (19), respiratory distress (14), and decreased feeding (15).

Evaluation of a commercially available direct immunofluorescent staining reagent for the detection of respiratory syncytial virus in respiratory secretions.

A commercially-available direct immunofluorescence (IF) reagent (Imagen; Boots-Celltech, Slough, Berkshire, United Kingdom) was similar in sensitivity and specificity to the conventional indirect IF test for the detection of respiratory syncytial virus in respiratory secretions. Both IF tests were more sensitive than culture, particularly for specimens transported from outside the institution.

Comparison of washed nasopharyngeal cells and whole nasal secretions for detection of respiratory syncytial virus antigens by enzyme-linked immunosorbent assay.

We compared washed nasal epithelial cells with unfractionated nasal secretions as sources of respiratory syncytial virus (RSV) antigens in an indirect enzyme-linked immunosorbent assay (ELISA). Of 28 infants positive for RSV by virus isolation or direct immunofluorescence or both, 27 (96%) were positive by ELISA with whole nasal secretions, whereas only 19 (68%) were positive by ELISA with the matching washed-cell fractions. Furthermore, the ELISA absorbances obtained with nasal secretions were significantly greater than those seen with washed-cell fractions, indicating that whole nasal secretions contain relatively greater amounts of RSV antigens as measured by ELISA.

Monoclonal antibodies for the rapid diagnosis of respiratory syncytial virus infection by immunofluorescence.

Eight separate monoclonal antibodies to the Long strain of respiratory syncytial virus (RSV) were tested for their utility as rapid diagnostic reagents in immunofluorescence. Preliminary screening indicated that all 8 reacted with 11 field strains from three previous local RSV outbreaks and with 4 of 5 additional strains chosen because of their antigenic diversity by neutralization. Two monoclonal antibodies, one each directed against a surface glycoprotein and the nucleocapsid protein, were then compared, singly and combined, with a polyclonal antiserum as diagnostic reagents in 209 consecutive samples submitted to our diagnostic laboratory.

Enzyme-linked immunosorbent assay for detection of respiratory syncytial virus infection: application to clinical samples.

An enzyme-linked immunosorbent assay (ELISA) for respiratory syncytial virus antigens was applied to the rapid diagnosis of acute infections in children and was compared with viral culture and immunofluorescence tests. The ELISA test employed commercially available reagents and was run on a day-to-day basis as specimens were received in the laboratory. Sensitivity and specificity by ELISA were 82 and 95%, respectively, compared with culture.

Isolation and transformation of primary mesenchymal cells of the chick embryo.

Pure primary mesenchymal cells from definitive streak stage chick embryos have been prepared free of epiblast and hypoblast cells. These cells have the potential in culture to differentiate into erythroid cells, beating heart muscle tissue, chondrocytes and epithelial cells. Transformation in vitro of pure primary mesenchymal cells by avian erythroblastosis virus (wt-AEV) and a temperature-sensitive mutant (ts34-AEV) gave rise to rapidly growing cells which remained largely undifferentiated, could be cloned in semi-solid medium and could be maintained for up to 3 months in culture.