Detection, semiquantitation, and genetic variation in hepatitis C virus sequences amplified from the plasma of blood donors with elevated alanine aminotransferase.

Hepatitis C virus (HCV) is the predominant etiologic agent of posttransfusion non-A, non-B hepatitis, characterized by undulating elevation of alanine aminotransferase (ALT) and chronic liver disease. A commercial enzyme-linked immunosorbent assay detected antibodies to HCV (anti-HCV) in 11 specimens among 101 nontransfusable plasma units obtained from asymptomatic, volunteer blood donors with elevated levels' of ALT. Using a combined reverse-transcription polymerase chain reaction (RT-PCR) assay developed by us, HCV RNA was detected in 0.6 ml of plasma from 8 of 11 (73%) of the anti-HCV-positive but in none of the 90 anti-HCV-negative specimens. The relatively low concentration of HCV RNA could be detected in the remaining three anti-HCV-positive specimens when 2.4 ml of plasma was analyzed. The plasma concentration of virions was estimated to range from 10(2) to 5 x 10(7)/ml. Direct sequencing performed on the PCR-amplified HCV cDNAs (210 base pairs) from three specimens revealed heterogeneity between 2.5 and 8.6% at the nucleotide level and less than 4% at the amino acid level. Our findings demonstrate that RT-PCR can be performed with 2.4 ml of plasma, providing an assay for the direct detection of HCV RNA and confirming the existence of an asymptomatic carrier state for HCV infection in the apparently healthy anti-HCV-positive donors.

Central nervous system involvement in a patient with chronic lymphocytic leukemia and non-Hodgkin's lymphoma (Richter's syndrome), with concordant cell surface immunoglobulin isotypic and immunophenotypic markers.

Central nervous system (CNS) involvement in Richter's syndrome has not been previously described. This report describes a 45-year-old man with the simultaneous occurrence of B-cell chronic lymphocytic leukemia (CLL), extramedullary large cell non-Hodgkin's lymphoma (NHL), and malignant lymphoid meningeal involvement. In this case, peripheral blood lymphocytes, cerebrospinal fluid (CSF) lymphoblasts, and malignant cells in surgical biopsy tissue obtained from a soft tissue mass all stained concordantly for immunoglobulin isotypes and for B-cell immunophenotypic markers, supporting the hypothesis of a clonal origin for the three malignant cell populations. These observations suggest that the different tumors in Richter's syndrome (CLL and NHL) may represent the clonal progression of a common neoplasm rather than independent neoplastic events. Richter's syndrome and other transformations of lymphoid malignancies (prolymphocytic transformation of CLL, blast crisis of CLL, and blastic transformation of NHL) may all represent possible routes of progression in the natural history of a single neoplasm. The present case also suggests that, in patients with B-cell CLL with CNS symptoms, the possibility of blastic transformation presenting as CNS lymphoma deserves consideration.

Experimental modification of rat pituitary growth hormone cell function during and after spaceflight.

Space-flown rats show a number of flight-induced changes in the structure and function of pituitary growth hormone (GH) cells after in vitro postflight testing (W. C. Hymen, R. E. Grindeland, I. Krasnov, I, Victorov, K. Motter, P. Mukherjee, K. Shellenberger, and M. Vasques. J. Appl. Physiol. 73, Suppl.: 151S-157S, 1992). To evaluate the possible effects of microgravity on growth hormone (GH) cells themselves, freshly dispersed rat anterior pituitary gland cells were seeded into vials containing serum +/- microM hydrocortisone (HC) before flight. Five different cell preparations were used: the entire mixed-cell population of various hormone-producing cell types, cells of density < 1.071 g/cm3 (band 1), cells of density > 1.071 g/cm3 (band 2), and cells prepared from either the dorsal or ventral part of the gland. Relative to ground control samples, bioactive GH released from dense cells during flight was reduced in HC-free medium but was increased in HC-containing medium. Band 1 and mixed cells usually showed opposite HC-dependent responses. Release of bioactive GH from ventral flight cells was lower; postflight responses to GH-releasing hormone challenge were reduced, and the cytoplasmic area occupied by GH in the dense cells was greater. Collectively, the data show that the chemistry and cellular makeup of the culture system modifies the response of GH cells to microgravity. As such, these cells offer a system to identify gravisensing mechanisms in secretory cells in future microgravity research.

Oxygen-induced marrow red cell hypoplasia leading to transfusion in sickle painful crisis.

The benefit of oxygen (O2) therapy in non-hypoxic sickle cell patients in painful crisis is uncertain. We report a case of a non-hypoxic sickle cell patient in painful crisis who developed marrow red cell hypoplasia requiring transfusion support after O2 therapy. The uncertain benefits of O2 use in such cases must be weighed against the serious and underrecognized risks of transfusion. In patients who develop O2-induced marrow red cell hypoplasia, cessation of O2 therapy may reverse the anemia and obviate the need for transfusion.

Development of antithrombin antibodies following surgery in patients with prosthetic cardiac valves.

Although antibody inhibitors directed against blood coagulation factors are well known, antibody inhibitors directed against thrombin are rare. We describe three postsurgical patients with prosthetic cardiac valves who developed serum autoantibodies reactive with human and bovine thrombin, as demonstrated by coagulation studies and immunoblotting. Despite marked prolongation of the thrombin time in these patients, the inhibitors were not associated with significant clinical bleeding. The mechanism of antithrombin autoantibody formation following surgery in patients with prosthetic cardiac valves remains to be determined.

Human immunodeficiency virus seroprevalence among blood product recipients in San Francisco before transfusion.

To determine the incidence of transfusion-associated human immunodeficiency virus (HIV) infection after routine screening of donated blood, a pilot study estimated the pretransfusion prevalence of HIV infection among blood product recipients in San Francisco. Among the 911 nonduplicate pretransfusion specimens from recipients without a clinical history of acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC), the overall prevalence of antibody to HIV was 2.9 percent (5.2% among males and 0.6% among females; p = 0.00002). If recipients in specifically defined or possible high-risk groups (n = 348) were excluded, a seropositivity rate of 1.8 percent (10/563) was detected, with all the positives occurring in men (10/242, 4.1%) and none in women (0/321, 0%). This demonstrated prevalence of HIV infection among blood product recipients in San Francisco before transfusion was substantially higher than the known 0.02 to 0.04 percent prevalence in the donor population. Therefore, the population of women without known risk for AIDS is the best in which to assess the risk of HIV infection in patients who are currently receiving seronegative blood transfusions.