Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver

The ability to identify, isolate, and transplant progenitor cells from solid tissues would greatly facilitate the treatment of diseases currently requiring whole organ transplantation. In this study, cell fractions enriched in candidate epithelial progenitor cells from the rat pancreas were isolated and transplanted into the liver of an inbred strain of Fischer rats. Using a dipeptidyl dipeptidase IV genetic marker system to follow the fate of transplanted cells in conjunction with albumin gene expression, we provide conclusive evidence that, after transplantation to the liver, epithelial progenitor cells from the pancreas differentiate into hepatocytes, express liver-specific proteins, and become fully integrated into the liver parenchymal structure. These studies demonstrate the presence of multipotent progenitor cells in the adult pancreas and establish a role for the liver microenvironment in the terminal differentiation of epithelial cells of foregut origin. They further suggest that such progenitor cells might be useful in studies of organ repopulation following acute or chronic liver injury.     

A human myeloma immunoglobulin G binding four moles of calcium associated with asymptomatic hypercalcemia

A calcium-binding immunoglobulin G (IgG_I^RUP) was identified in the serum of a patient with multiple myeloma, asymptomatic hypercalcemia, and a normal ionized serum calcium. Calcium binding by IgG^RUP was confirmed by two-dimensional electrophoresis with calcium-45 and equilibrium dialysis. Amino acid analyses indicated an unusually high number of glutamic (or glutamine) residues in the L chain and Fab fragment but no detectable -carboxyglutamic acid. As determined by equilibrium dialysis with⁴⁵Ca, the intact IgG^RUP and its Fab fragments bound calcium at an optimum pH of 7.4. There was minimal binding of calcium to H chains and no binding by L chains or the Fc fragment. Recombination of H and L chains partially restored the binding activity. By Scatchard analysis, the binding affinity (K _d) of IgG^RUP was 1.7×10^–3 M and the binding capacity was 4 mol of calcium/mol of IgG. The binding of 4 mol of calcium/mol of IgG is twice that reported previously for two other calcium-binding myeloma proteins and suggests unique properties of IgG^RUP.     

Sputum Cytokine Levels in Patients with Pulmonary Tuberculosis as Early Markers of Mycobacterial Clearance

Sputum and serum from patients with active pulmonary tuberculosis (TB), healthy purified protein derivative-positive adults, and patients with bacterial pneumonia were collected to simultaneously assess local immunity in the lungs and peripheral blood. To determine whether cytokine profiles in sputum from TB patients and control subjects were a reflection of its cellular composition, cytospin slides were prepared in parallel and assessed for the presence of relative proportions of epithelial cells, neutrophils, macrophages, and T cells. Gamma interferon (IFN-γ) in sputum from TB patients was markedly elevated over levels for both control groups. With anti-TB therapy, IFN-γ levels in sputum from TB patients decreased rapidly and by week 4 of treatment were comparable to those in sputum from controls. Further, IFN-γ levels in sputum closely followed mycobacterial clearance. Although detected at fourfold-lower levels, IFN-γ immunoreactivities in serum followed kinetics in sputum. TNF-α, interleukin 8 (IL-8) and IL-6 also were readily detected in sputum from TB patients at baseline and responded to anti-TB therapy. In contrast to IFN-γ, however, TNF-α and IL-8 levels also were elevated in sputum from pneumonia controls. These data indicate that sputum cytokines correlate with disease activity during active TB of the lung and may serve as potential early markers for sputum conversion and response to anti-TB therapy.     

Effect of tryptophan on hepatoma and host liver of rats: Influence after treatment with hypertonic sodium chloride and carbon tetrachloride

Female inbred Buffalo rats bearing intrahepatically transplanted hepatoma 5123 were subjected intraperitoneally to the acute administration of hypertonic NaCl or CCl₄ followed by a tube-feeding of l-tryptophan. The responses in terms of changes in polyribosomal aggregation and protein synthesis (in vitro) of host liver and hepatoma were evaluated. While treatment with hypertonic NaCl or CCl₄ caused disaggregation of polyribosomes and inhibition of protein synthesis in both host liver and hepatoma, the subsequent administration of tryptophan caused some improvement in both parameters in host liver but not in hepatoma. Administration of hypertonic NaCl alone caused a decrease in [¹⁴C]orotate incorporation into poly(A)-mRNA of host liver and hepatoma, whereas administration of tryptophan after hypertonic NaCl caused a significant improvement in host liver alone. Following the tryptophan administration, the activities of nuclear DNA-dependent RNA polymerases I and II, and of nuclear-envelope nucleoside triphosphatase, as well as labeled nuclear RNA release in vitro were slightly elevated in host liver but not in hepatoma. Tryptophan-related compounds, 5-hydroxy-dl-tryptophan, 5-fluorotryptophan, indole, and 3-hydroxyanthranilic acid, when administered in place of l-tryptophan, did not appreciably affect polyribosomal aggregation or protein synthesis in vitro in host liver or hepatoma.     

Prevalence rates and psychosocial characteristics associated with depression in pregnancy and postpartum in Maltese women

BACKGROUND: Investigators have commented on the apparent high prevalence of psychiatric symptoms in pregnancy. In Malta there is lack of epidemiological data and therefore, the prevalence of depression during pregnancy and at 8 weeks postpartum among a community sample of Maltese women was carried out. METHOD: A random sample of 239 pregnant women were interviewed at booking using a detailed sociodemographic history, the revised version of the clinical interview schedule (CIS-R) and Maltese translation of the Edinburgh postnatal depression scale (EPDS). The CIS-R was again administered over the phone at 36 weeks and the EPDS sent by post. At 8 weeks postpartum, the CIS-R, modified version of the social maladjustment schedule and the EPDS were again administered to 95.8% of women. RESULTS: The point prevalence of depression meeting ICD-10 research criteria was 15.5% at booking, 11.1% in the third trimester and 8.7% postpartum of which only 3.9% had an onset since delivery. CONCLUSIONS: The low rate of new onset postpartum depression compared with other studies in our sample may be attributable to the social support available to women living in a cohesive Catholic island community. LIMITATION: The follow-up was limited to 8 weeks postpartum. No control group was used to compare the prevalence of depression in women who did not recently have a baby.     

Spectrum of Kaposi's sarcoma-associated herpesvirus,or human herpesvirus 8, diseases

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV), discovered in 1994, is a human rhadinovirus (gamma-2 herpesvirus). Unlike other human herpesviruses (herpes simplex virus, Epstein-Barr virus, varicella-zoster virus, cytomegalovirus, HHV-6, and HHV-7), it is not widespread in the general population and has many unique proteins. HHV-8 is strongly associated with all subtypes of Kaposi's sarcoma (KS), multicentric Castleman's disease, and a rare form of B-cell lymphoma, primary effusion lymphoma. In addition, HHV-8 DNA sequences have been found in association with other diseases, but the role of the virus in these diseases is largely unconfirmed and remains controversial. The seroprevalence of HHV-8, based on detection of latent and lytic proteins, is 2 to 5% in healthy donors except in certain geographic areas where the virus is endemic, 80 to 95% in classic KS patients, and 40 to 50% in HIV-1 patients without KS. This virus can be transmitted both sexually and through body fluids (e.g., saliva and blood). HHV-8 is a transforming virus, as evidenced by its presence in human malignancies, by the in vitro transforming properties of several of its viral genes, and by its ability to transform some primary cells in culture. It is not, however, sufficient for transformation, and other cofactors such as immunosuppressive cytokines are involved in the development of HHV-8-associated malignancies. In this article, we review the biology, molecular virology, epidemiology, transmission, detection methods, pathogenesis, and antiviral therapy of this newly discovered human herpesvirus.