Pharmacokinetic properties of human fibroblast and leukocyte interferon in rabbits.

When rabbits were given intramuscular injections of the same quantities of human leukocyte or fibroblast interferons, the former produced moderately higher levels of circulating interferon. Fibroblast interferon was not cleared faster from circulation, nor was direct inactivation by rabbit blood responsible for this difference.     

Multiple abnormalities in a child with partial duplications of 10p and 13q from a 3:1 segregation of a maternal t(10;13) translocation.

Partial duplications of 10p and 13q in association with partial deletions of other chromosome segments have been variously reported. We describe here a female child with multiple congenital abnormalities and combined partial duplications of 10p and 13q resulting from a 3:1 segregation of a maternal t(10;13)(p13;q22). In comparing the phenotypic features of the two chromosome imbalances, the expression of features typical of partial duplication 10p appeared more pronounced.     

The shufflon of Salmonella enterica serovar Typhi regulates type IVB pilus-mediated bacterial self-association

Previously, it was shown that type IVB pili encoded by the Salmonella enterica serovar Typhi pil operon are used to facilitate bacterial entry into human intestinal epithelial cells in vitro and that such entry is inhibited by purified prepilin (pre-PilS) protein (X.-L. Zhang, I. S. M. Tsui, C. M. C. Yip, A. W. Y. Fung, D. K.-H. Wong, X. Dai, Y. Yang, J. Hackett, and C. Morris, Infect. Immun. 68:3067-3073, 2000). The pil operon concludes with a simple shufflon, and a recombinase gene product (Rci) inverts DNA in the C-terminal region of the pilV gene to allow synthesis of two distinct PilV proteins, PilV1 and PilV2, which are presumptive minor pilus proteins. We show here that the type IVB pili mediate bacterial self-association, but only when the PilV1 and PilV2 proteins are not expressed. This may be achieved in wild-type serovar Typhi by rapid DNA inversion activity of the shufflon. We show that the inversion activity inhibits the expression of genes inserted between the 19-bp inverted repeats used for Rci-mediated recombination and that the activity of Rci increases when DNA is supercoiled. The data suggest that serovar Typhi self-associates under conditions (such as low oxygen tension in the gut) that favor DNA supercoiling. These results explain (i) the function of the serovar Typhi shufflon and (ii) why there are only two possible shufflon states, in contrast to the many possible states of other shufflon systems. The data further indicate that a very early step in serovar Typhi pathogenesis may be type IVB pilus-mediated self-association of bacteria in the anaerobic human small intestine prior to invasion of the human gut epithelium. The suggested type IVB pilus-dependent step in typhoid fever pathogenesis may partially explain the enhanced invasiveness of serovar Typhi for humans.     

Discordant immunologic and virologic responses to highly active antiretroviral therapy are associated with increased mortality and poor adherence to therapy

OBJECTIVE: To examine the independent association of discordant virologic and immunologic responses to highly active antiretroviral therapy (HAART) with mortality. METHODS: A population-based study of 1527 treatment-naive individuals initiating HAART used Cox proportional hazards modeling to determine the independent association of treatment response at 3 to 9 months with nonaccidental mortality. Logistic regression was used to examine associations with discordant responses. RESULTS: Viral load (VL)/CD4 discordant responses were seen in 235 (15.4%) of subjects, and VL/CD4 responses were seen in 179 (11.7%) of subjects. In adjusted Cox regression models, discordant responses were found to be independently associated with an increased risk of mortality (VL/CD4: relative hazard [RH] = 1.87, 95% confidence interval [CI]: 1.15 to 3.04; VL/CD4: RH = 2.47, 95% CI: 1.54 to 3.95). VL/CD4 discordance was found to be associated with increasing age, baseline HIV RNA load <100,000 copies/mL, baseline CD4 counts <50 cells/muL, the use of lamivudine (3TC)/zidovudine (ZDV), and poor adherence to therapy. VL/CD4 discordance was associated with younger age; injection drug use; baseline HIV RNA load >100,000 copies/mL; the use of 3TC/ZDV, didanosine (ddI)/3TC, or ddI/stavudine; and poor adherence to therapy. CONCLUSION: Discordant responses are independently associated with an increased risk of mortality and are, in turn, associated with poor adherence to therapy.     

Cytology of mucinous carcinoma of breast: a report of 28 cases with histological correlation

Pure mucinous carcinoma (MC) of the breast is a relatively uncommon variant of breast carcinoma with distinctive histological and cytological features. In this study we have analysed fine needle aspiration (FNA) cytological material from 28 cases of MC of breast and correlated the cytomorphological features with histopathology. The 28 patients consisted of 27 females and one male patient. 14 patients were Chinese, 10 were Indian and four were Malay. Their ages ranged from 38 to 90 with a mean at 52 years. The left breast was involved in 17 and the right in 11 cases. The duration of the lump varied from two weeks to 10 years. The cytological picture was characterized by abundant extracellular mucin giving a "sea of mucin" or "whirlpools of mucin" effect, in which were seen floating clusters of tumour cells with relatively bland cytological features. Myxo-vascular fragments were seen in 12 cases. Dissociated tumour cells showed a plasmacytoid appearance with eccentric nuclei. In four cases, the mucin was scanty in amount and the cellularity was high while in two cases, the cellularity was very low. Psammoma bodies were seen in cytological smears in one case. Histological study of excision or mastectomy specimens confirmed all 28 cases to be pure MC. Knowledge of the distinctive cytomorphological appearance of MC would enable correct identification of these lesions as malignant and prompt treatment that could further enhance the survival of these prognostically good breast cancers.     

Characterization of two epitopes on insulin using monoclonal antibodies

Three monoclonal antibodies (MAb), 21 (IgG1), I10 (IgG1) and H38 (IgG2b), to insulin have been tested for cross-reactivity with 11 species variants of insulin and three of proinsulin. Correlations of differences of reactivities between the MAb and the species variants of insulin with the respective amino acid sequences of the latter have permitted the identification of two epitopes recognized by the MAb which encompass the regions in the A- and B-chains of insulin subject to frequent evolutionary amino acid substitutions. MAb 21 and H38 are directed to an epitope which includes residues B27-30 and A1 or A4 and can discriminate between human and pig insulins which differ only at B30. MAb 21 reacts with human (B30 thr) but not with pig (B30 ala) insulins, whereas MAb H38 exhibits a reciprocal specificity. Neither MAb 21 nor MAb H38 react with human or pig proinsulins respectively indicating that the presence of the C-peptide joining A1 to B30 masks the epitope. MAb 21 reacts with human insulin 125I-labeled at tyr A14 but not B26 suggesting that incorporation of the I atom at B26 also masks the epitope. MAb I10 is directed to an epitope which includes A8-10 and A4 or B3 with a specificity for the human A8-10 sequence. MAb I10 reacts with human proinsulin and human insulin 125I-labeled at either tyr A14 or B26.     

Correlation of physicohemical and antigenic properties of human leukocyte interferon subspecies

Summary Human leukocyte interferon produced in primary cultures of buffy coat cells and human fibroblast interferon from cultures of the FS-4 foreskin cell strain were subjected to isoelectric focusing in polyacrylamide gels. Leukocyte interferon could be resolved into three major components (pI 5.5, 6.2 and 6.6, respectively) and one minor component (pI 7.0). Fibroblast interferon activity focused in a broad pH range of 6.8–7.8.The isoelectrically distinct subspecies of human leukocyte interferon were isolated and compared as to their antigenic nature, heterospecific antiviral activity in cultures of bovine cells, and apparent molecular weights upon electrophoresis in sodium dodecyl sulfate-polyacrylamide gels (SDS-PAGE). The three major subspecies (pI 5.5, 6.2 and 6.6) were similar in their neutralization by antiserum against whole leukocyte interferon and in their relative heterospecific activities on bovine cells. When analyzed on SDS-PAGE, the component focusing at pH 5.5 migrated to a position corresponding to a molecular weight of 17,500 (Le _f), the component with the pI of 6.6 had its major peak corresponding to a molecular weight of 23,000 (Le _s), while the pI 6.2 component contained a mixture of the two molecular weight species. The minor isoelectric component focusing at pI 7.0 contained interferon with the antigenic specificity of fibroblast (F) interferon. It is concluded that the two major antigenic species of human interferon (Le andF) and two known subspecies of human leukocyte interferon (Le _s andLe _f) can be resolved by isoelectric focusing.With 3 Figures     

The absence of a B allele in acquired B blood group phenotype confirmed by a DNA based genotyping method.

A case of an 87 year old woman with carcinomatous sigmoid colon, found to be of group A1 with acquired B status, is reported. The acquired B phenotype was confirmed by the absence of a B allele in the patient using denaturing gradient gel electrophoresis of a DNA fragment amplified from the ABO locus by the polymerase chain reaction.