Promoter for a Brassica napus ribulose bisphosphate carboxylase/oxygenase small subunit gene binds multiple nuclear factors and contains a negative-strand open reading frame encoding a putative transmembrane protein.

Using a fractionated genomic bank, we have cloned and characterized a Brassica napus gene (rbcSF1) encoding the small sub-unit of ribulose 1,5-bisphosphate carboxylase. The promoter of this gene contains a 29 bp direct repeat capable of forming a single or a double hairpin loop, and three elements that are recognized by leaf nuclear proteins in vitro. The most upstream are the S-box, a small A/T-rich sequence between -516 and -512, and the F-box between -492 and -475. Finally, we have also observed binding to the G-box, a regulatory element common to numerous plant promoters. The promoter of rbcSF1 also has a 113 amino acids open reading frame (ORF113) in the non-coding strand. When used to probe a northern blot of leaf RNA, this ORF hybridizes to a 1.5 kb transcript. The protein encoded by ORF113 contains a transmembrane domain.

A phase III randomized trial of epirubicin versus 5-fluorouracil in metastatic rectal/sigmoid adenocarcinoma.

Seventy-seven patients with previously untreated, measurable, histologically confirmed, metastatic adenocarcinoma of the rectum or sigmoid were randomized to receive either epirubicin 90 mg/m2 (75 mg/m2 if prior radiotherapy) i.v. once every 3 weeks or 5-fluorouracil 500 mg/m2 (450 mg/m2 if prior radiotherapy) i.v. once daily for 5 consecutive days every 4 weeks. None of 38 (0%) evaluable patients who received epirubicin demonstrated a response, whereas seven of 39 (18%) patients who received 5-fluorouracil had an objective response. Epirubicin is ineffective against metastatic rectal cancer at the dose and schedule used.

Prognostic factors and staging classification of patients with epidemic Kaposi's sarcoma.

Two hundred twelve patients with acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) were followed prospectively. Univariate and multivariate analyses were performed to determine significant predictors of survival and development of opportunistic infection (OI) from the time of diagnosis of KS. Clinical variables analyzed were age at onset, presence of systemic symptoms, prior or coexistent OI, development of OI greater than 3 months following KS diagnosis, and extent of disease. Laboratory variables analyzed were absolute number of peripheral T-helper lymphocytes (T4), helper/suppressor ratio (T4/T8), serum beta-2-microglobulin, and serum acid labile alfa interferon. Three independent variables were predictive of shorter survival: (1) prior or coexistent OI (P = .02), (2) presence of systemic symptoms (P = .001), and (3) absolute T4 count less than 300 cells/microL (P = .002). Based on survival, patients with AIDS-related KS can be divided into four groups: (1) those with no prior or coexistent OI, no systemic symptoms, T4 greater than or equal to 300 cells/microL (median survival, 31 months): (2) those with no prior or coexistent OI, no systemic symptoms, and T4 less than 300 cells/microL (median survival, 20 months); (3) those with no prior or coexistent OI and presence of systemic symptoms (median survival, 15 months); and (4) those with prior or coexistent OI (median survival, 7 months).

Ganciclovir treatment of gastrointestinal infections caused by cytomegalovirus in patients with AIDS.

Ganciclovir (DHPG) treatment of 69 AIDS patients with gastrointestinal infection due to cytomegalovirus (CMV) was studied. Sites of infection included the colon (46 patients, 67%), esophagus and stomach (15 patients, 22%), rectum (five patients, 7%), liver (two patients, 3%), and small bowel (one patient, 1.4%). Ganciclovir was given in a dose of 5 mg/kg intravenously every 12 hours for 14 days. Maintenance therapy consisted of 6 mg/kg daily. Positive clinical responses were seen in 52 (75%) of the 69 patients, stable responses in 9 (13%), and worsening in eight (11%). The virologic response was positive in 47 patients (68%), while virologic findings did not change in three patients (4%) and could not be evaluated in 19 patients (28%). Toxicity was mainly hematologic, with moderate leukopenia (1,000-1,900 leukocytes/mm3) in seven patients and severe leukopenia (less than 1,000 leukocytes/mm3) in three patients. The median survival time was 18 weeks (range, 1-68 weeks). Forty-seven patients survived for 4 weeks; of these, 22 (47%) relapsed. The median time to relapse was 9 weeks. Despite the uncontrolled nature of this study, ganciclovir is probably an effective and safe agent for the treatment of gastrointestinal CMV infections. The high probability of relapse (50%) should be considered and maintenance therapy offered to most patients.

Parasitic infections in a New York City hospital: trends from 1971 to 1984.

We report the frequency of parasitic infections 1971-84 in a major New York City Medical Center whose catchment area includes many immigrants from Dominican Republic. Infection with 7,803 parasites was documented in 41,958 laboratory specimens. Trends were toward fewer total specimens being sent and fewer still being positive, although a rise in G. lamblia, E. histolytica, and Cryptosporidium is apparent in recent years. Parasitology laboratories should provide similar data to alert clinicians to the parasites prevalent locally.

Herpes zoster: a possible early clinical sign for development of acquired immunodeficiency syndrome in high-risk individuals.

Zoster is uncommon before the age of 50 years in immunologically normal individuals, but it occurs with increased frequency in people who are immunosuppressed. A retrospective review of 300 patients with acquired immunodeficiency syndrome associated with Kaposi's sarcoma, revealed that 8% had prior zoster, a rate that is sevenfold greater than historic controls of the same age. We prospectively examined forty-eight patients, with no known immunodeficiency or signs of AIDS or AIDS related complex (ARC), who presented with zoster localized to the thoracic region. Forty-one patients had known risk factors for AIDS and thirty-five had antibody to the AIDS-associated virus (AAV) at the time of presentation. One seropositive subject had no known risk factors. Absolute lymphocyte counts, lymphocyte OKT4/OKT8 ratios, and lymphocyte mitogen responses were all depressed in subjects with antibody to AAV when compared with seronegative individuals. Seven of thirty-three AAV antibody-positive subjects, who could be followed longitudinally, developed AIDS from 1 to 28 months (mean = 13) after zoster. One antibody-negative subject seroconverted to become AAV seropositive 16 months after zoster and developed Kaposi's sarcoma 1 month later. These eight subjects had persistently low lymphocyte OKT4/OKT8 ratios and elevated beta-2 microglobulin. In patients at risk for AIDS, the occurrence of zoster may be one sign that heralds the marked depression of cellular immunity associated with AIDS or ARC.

Involvement of transferrin and transferrin receptors in human natural killer effector:target interaction.

In this current study one of the determinants of natural killer cell specificity in immunosurveillance against cancer, may be the recognition of transferrin receptors on neoplastic cells by the NK effectors. Human transferrin, when saturated with iron (FeTf), was found to inhibit human natural killer (NK) activity against K562 tumor cells, if included in assay mixtures at physiologically relevant levels. Whereas both FeTf and iron-free transferrin (ApoTf) inhibited initial conjugate formation at the level of the target cell, only FeTf inhibited NK cytolytic activity, as judged by release of chromium from the targets. This suggested a functional role for FeTf on either NK or tumor cells. When either targets or effector lymphocytes were pre-incubated with FeTf, inhibition of killing was strongest when the targets were first exposed to FeTf. The evidence suggested that NK-associated transferrin mediated the interaction with target cells through free target-associated transferrin receptors. The finding that rabbit anti-human transferrin antibody (RaHTf) inhibited killing, when reacted with effector lymphocytes but not with target cells, supported this hypothesis.

Inosine synthesis and phosphoribosylpyrophosphate availability in rat liver cells in the presence of allopurinol.

In the presence of allopurinol, apparent phosphoribosylpyrophosphate (PP-ribose-P) availability as measured by adenine incorporation into ribonucleotides was decreased in rat liver cells, hypoxanthine incorporation into ribonucleotides was increased, and there was a large synthesis of inosine from hypoxanthine. Inosine was formed directly by the reversal of the purine nucleoside phosphorylase reaction which was very rapid in liver cells. We tested the hypothesis that utilization of ribose 1-phosphate for inosine synthesis could decrease PP-ribose-P availability. Our results indicate that the apparent decrease of PP-ribose-P availability in the presence of allopurinol was due to competition between adenine and hypoxanthine salvage pathways into nucleotides, and not to the synthesis of inosine.