Consensus guidelines for the treatment of yeast infections in the haematology, oncology and intensive care setting, 2014.

Pathogenic yeast forms are commonly associated with invasive fungal disease in the immunocompromised host, including patients with haematological malignancies and patients of haemopoietic stem cell transplants. Yeasts include the Candida spp., Cryptococcus spp., Pneumocystis jirovecii and some lesser-known pathogens. Candida species remain the most common cause of invasive yeast infections (and the most common human pathogenic fungi). These guidelines present evidence-based recommendations for the antifungal management of established, invasive yeast infections in adult and paediatric patients in the haematology/oncology setting. Consideration is also given to the critically ill patient in intensive care units, including the neonatal intensive care unit. Evidence for 'pre-emptive' or 'diagnostic-driven antifungal therapy' is also discussed. For the purposes of this paper, invasive yeast diseases are categorised under the headings of invasive candidiasis, cryptococcosis and uncommon yeast infections. Specific recommendations for the management of Pneumocystis jirovecii are presented in an accompanying article (see consensus guidelines by Cooley et al. appearing elsewhere in this supplement).

Prognosis of acute kidney injury in dogs using RIFLE (Risk, Injury, Failure, Loss and End-stage renal failure)-like criteria.

A retrospective case-series study evaluated the prognosis of 853 dogs with acute kidney injury (AKI) based on the RIFLE (Risk, Injury, Failure, Loss and End-stage renal failure) criteria, derived from human medicine. The 30-day mortality of dogs with AKI in each class was found to be 23.8 per cent (40 of 168) dogs for Risk, 41.0 per cent (107 of 261) dogs for Injury and 78.5 per cent (333 of 424) dogs for Failure. Using the dogs in the Risk class as the reference, the mortality of dogs in either the Injury or Failure class was significantly higher than that of dogs in the Risk class (P<0.05). The longest median survival time was observed in the Risk class (nine days) and the shortest median survival time was observed in the Failure class (three days). Using a multiple logistic regression model, a new score that simultaneously considered RIFLE class, diarrhoea status and serum phosphorus level was calculated to predict prognosis. Evaluation using the area under the receiver-operating characteristic curve (AUROC) indicated that the new scoring method (AUROC 0.80) was a better prognostic indicator than using RIFLE criteria alone (AUROC 0.73).

N-3 vs. saturated fatty acids: effects on the arterial wall.

Cardiovascular disease is a leading cause of death worldwide. Atherosclerosis and unstable plaques are underlying causes for cardiovascular diseases. Cardiovascular disease is associated with consumption of diets high in saturated fats. In contrast there is increasing evidence that higher intakes of dietary n-3 fatty acids decrease risk for cardiovascular disease. Recent studies are beginning to clarify how n-3 compared with saturated fatty acids influence cardiovascular disease risk via pathways in the arterial wall. In this paper we will review studies that report on mechanisms whereby dietary fatty acids affect atherosclerosis through modulation of arterial wall lipid deposition, inflammation, cell proliferation, and plaque vulnerability.

Redox-mediated enrichment of self-renewing adult human pancreatic cells that possess endocrine differentiation potential.

OBJECTIVES: The limited availability of transplantable human islets has stimulated the development of methods needed to isolate adult pancreatic stem/progenitor cells capable of self-renewal and endocrine differentiation. The objective of this study was to determine whether modulation of intracellular redox state with N-acetyl-L-cysteine (NAC) would allow for the propagation of pancreatic stem/progenitor cells from adult human pancreatic tissue. METHODS: Cells were propagated from human pancreatic tissue using a serum-free, low-calcium medium supplemented with NAC and tested for their ability to differentiate when cultured under different growth conditions. RESULTS: Human pancreatic cell (HPC) cultures coexpressed alpha-amylase, albumin, vimentin, and nestin. The HPC cultures, however, did not express other genes associated with differentiated pancreatic exocrine, duct, or endocrine cells. A number of transcription factors involved in endocrine cell development including Beta 2, Islet-1, Nkx6.1, Pax4, and Pax6 were expressed at variable levels in HPC cultures. In contrast, pancreatic duodenal homeobox factor 1 (Pdx-1) expression was extremely low and at times undetectable. Overexpression of Pdx-1 in HPC cultures stimulated somatostatin, glucagon, and carbonic anhydrase expression but had no effect on insulin gene expression. HPC cultures could form 3-dimensional islet-like cell aggregates, and this was associated with expression of somatostatin and glucagon but not insulin. Cultivation of HPCs in a differentiation medium supplemented with nicotinamide, exendin-4, and/or LY294002, an inhibitor of phosphatidylinositol-3 kinase, stimulated expression of insulin mRNA and protein. CONCLUSION: These data support the use of intracellular redox modulation for the enrichment of pancreatic stem/progenitor cells capable of self-renewal and endocrine differentiation.

Effect of dietary Echinacea purpurea on viremia and performance in porcine reproductive and respiratory syndrome virus-infected nursery pigs.

The effect of dietary Echinacea purpurea on performance, viremia, and ontogeny of the humoral antibody response against porcine reproductive and respiratory syndrome virus (PRRSV) infection was evaluated in weaned pigs. In three replicates, 120 weaned pigs (25 +/- 1 d of age; 8.46 +/- 0.48 kg of BW) from a PRRSV-naive herd were allotted randomly to one of eight pens (diets) in two separate rooms (four pens/room), with each pen containing five pigs. Pigs began one of four dietary treatments (as-fed basis) 1 wk before inoculation with PRRSV: 1) basal diet composed of corn, soybean meal, whey, and essential vitamins and minerals; 2) basal diet plus carbadox (0.055 g/kg of diet; as-fed basis); 3) basal diet plus Echinacea 2% (2% of the total diet); 4) basal diet plus Echinacea 4% (4% of the total diet). The diets were formulated to be isocaloric and isolysinic. Echinacea purpurea was purchased in powder form and determined by chemical analysis to contain 1.35% cichoric acid (as-fed basis). Seven days after starting the diets, all pigs in one room were intranasally inoculated with PRRSV isolate ATCC VR-2332 at a concentration of 10(4) tissue culture infectious dose50/mL. To monitor the effects of Echinacea and PRRSV challenge, BW and blood samples were obtained from all pigs at 7-d intervals. Serum samples were analyzed for the presence of PRRSV and PRRSV-specific antibodies. All challenged pigs became infected with PRRSV, and all unchallenged pigs remained free of infection. No differences (P > 0.10) in ADG, ADFI, or gain:feed (G:F) were observed in PRRSV-challenged compared with unchallenged animals. For PRRSV-challenged animals receiving diets supplemented with Echinacea at 2 or 4%, no differences (P > 0.10) were observed in ADG, ADFI, or G:F ratio. Among PRRSV-challenged pigs, dietary Echinacea did not affect (P > 0.10) the rate or level of the ELISA-detectable antibody response from d 7 to 42 or the level and duration of PRRSV in serum. For PRRSV-unchallenged animals receiving diets supplemented with Echinacea at 2 or 4%, no differences (P > 0.10) were observed in ADG, ADFI, and G:F ratio. Under the conditions of this study, dietary Echinacea did not enhance growth, exhibit antiviral effects to PRRSV, or show any evidence of immune enhancing properties.

Reduction in erythropoietin doses by the use of chronic intravenous iron supplementation in iron-replete hemodialysis patients.

BACKGROUND: Iron deficiency is the most common cause of suboptimal response to recombinant human erythropoietin (rHuEPO) in chronic hemodialysis (HD) patients. Iron supply can correct this situation, however, optimal dosage, route of administration, and monitoring of iron status during rHuEPO therapy in maintenance HD patients remains controversial. METHODS: We conducted a 12-month intravenous iron substitution trial in 149 iron-replete chronic HD patients receiving subcutaneous rHuEPO therapy. The available iron pool was maintained with 100 mg iron every 2 weeks or 1 month depending on serum ferritin and transferrin saturation levels, the rHuEPO dosage titrated depending on hematocrit (Hct) levels. RESULTS: After 12-month protocol, the Hct increased (28.7 +/- 4.1 vs 27.7 +/- 2.6, p = 0.003), rHuEPO requirement reduced 25% (46.1 +/- 28.9 vs 61.5 +/- 67.8 U/kg/week, p = 0.006), serum ferritin increased (1,383 +/- 727 vs 930 +/- 857 ng/ml, p < 0.001), so did the transferrin saturation (36.1 +/- 12.7 vs 27.5 +/- 12.8%, p < 0.001). The serum albumin decreased slightly but reached statistical significance (4.1 +/- 0.48 vs 4.2 +/- 0.36 g/dl, p = 0.006), so did the cholesterol levels (166 +/- 41 vs 173 +/- 38 mg/dl, p = 0.044) and pre-dialysis creatinine (11.3 +/- 2.3 vs 11.5 +/- 2.4 mg/dl, p = 0.015). Besides, the iPTH levels did not interfere with the rHuEPO dosage reduction and Hct increment in our patients. CONCLUSION: We conclude that maintaining high levels of serum ferritin and transferrin saturation could further reduce the requirement of rHuEPO in chronic HD patients, but the long-term effect of iron overloading to patients' nutritional status must be further evaluated in contrast to the economic saving.

Diabetic ketoacidosis and hypogonadotropic hypogonadism in association with transfusional hemochromatosis in a man with beta-thalassemia major.

We report a 23-year-old man with beta-thalassemia major and transfusional hemochromatosis, which manifested as diabetic ketoacidosis and hypogonadotropic hypogonadism. This unusual presentation of diabetic ketoacidosis in hemochromatosis has rarely been reported. Magnetic resonance imaging of the abdomen showed decreased signal intensity in the liver, spleen, and pancreas. In addition, the pituitary gland also showed heterogeneous low signal intensity, compatible with hemochromatosis. He was treated with insulin supplements and pulsatile human chorionic gonadotropin administration. Clinical improvement was noted after hormone replacement. Intensive iron chelation therapy was given to prevent cardiac complications, and to restore his gonadal function. During follow-up, the patient experienced improvement in libido and sexual potency.

Transurethral microwave thermotherapy for symptomatic benign prostatic hyperplasia: long-term durability with Prostcare.

OBJECTIVE: To evaluate the long-term durability of transurethral microwave thermotherapy (TUMT) with Prostcare for symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: From August 1993 to July 1994, a total of 65 patients with symptomatic BPH who underwent TUMT using the Prostcare apparatus (Bruker Spectospin, Wissembourg, France) with low-energy protocol (maximal power 52 W) were enrolled into a short-term evaluation. Subsequent follow-up information was collected in July 1999. If patients had had any further therapy for BPH, the date of retreatment was considered as an endpoint of TUMT efficacy. If no further therapy for BPH had been needed, they were re-assessed for overall satisfaction. RESULTS: The median follow-up period was 49 months. Twenty patients were excluded for various reasons, including 17 with loss of follow-up and 3 with new diseases that could affect the voiding status. Thirty-eight (84.4%) of 45 valuable patients had received further therapy for BPH, including medication (n = 21, 46.7%), and endoscopic surgery (n = 17, 37.7%). The times to pharmacologic or endoscopic retreatment after TUMT were 8.9+/-11.1 and 23.0+/-14.4 months, respectively (p = 0.0003, log rank test). Only 7 (15.5%) patients had no further treatment, with 3 having satisfactory improvements, but 4 feel dissatisfied yet not needing any further therapy. In addition, 2 patients complained of erectile dysfunction after TUMT and 1 was diagnosed with prostate cancer 50 months after TUMT. In addition, there was no significant difference for all baseline values among three groups with no retreatment or retreatment with medication or endoscopic surgery. CONCLUSION: At the 5-year follow-up, the long-term durability of low-energy TUMT with Prostcare is only exhibited in a few patients and the overall retreatment rate was 84.4%. Thus, patient should be informed of the high probability of supplementary treatment after TUMT.

Molecular cloning and functional characterization of a novel delayed rectifier potassium channel from channel catfish (Ictalurus punctatus): expression in taste buds.

The gustatory system of channel catfish is widely studied for its sensitivity to amino acids. As a first step in identifying the molecular components that play a role in taste transduction in catfish, we cloned the full-length cDNA for Kv2-catfish, a novel K(+) channel that is expressed in taste buds. The deduced amino acid sequence is 816 residues, and shares a 56-59% sequence identity with Kv2.1 and Kv2.2, the other members of the vertebrate Kv2 subfamily of voltage-gated K(+) channels. The Kv2-catfish RNA was expressed in taste buds, brain, skeletal muscle, kidney, intestine and gills, and its gene is represented as a single copy in the catfish genome. Recombinant channels expressed in Xenopus oocytes were selective for K(+), and were inhibited by tetraethylammonium applied to the extracellular side of the membrane during two-electrode voltage clamp analysis with a 50% inhibitory constant of 6.1 mM. The channels showed voltage-dependent activation, and did not inactivate within 200 ms. Functionally, Kv2-catfish is a voltage-gated, delayed rectifier K(+) channel, and its primary structure is the most divergent sequence identified among the vertebrate members of the Kv2 subfamily of K(+) channels, being related equally well to Kv2.1 and Kv2.2.

Shedding of porcine reproductive and respiratory syndrome virus in mammary gland secretions of sows.

OBJECTIVE: To document shedding of porcine reproductive and respiratory syndrome (PRRS) virus in mammary gland secretions of experimentally inoculated sows, to evaluate effects of vaccination during gestation on virus shedding during the subsequent lactation, and to evaluate shedding of PRRS virus in milk of sows in commercial herds. ANIMALS: 6 sows seronegative for PRRS virus were used for experiment 1, and 2 sows were retained for experiment 2. For experiment 3, 202 sows in commercial herds were used. PROCEDURE: In experiment 1, 2 sows were inoculated with PRRS virus, 2 sows were vaccinated with modified-live PRRS virus vaccine, and 2 sows served as control pigs. Mammary gland secretions were assayed for PRRS virus. In experiment 2, pregnant vaccinated sows from experiment 1 were vaccinated with another modified-live PRRS virus vaccine. Mammary gland secretions were assayed in the same manner as for experiment 1. For experiment 3, milk collected from 202 sows in commercial herds was assayed for PRRS virus. RESULTS: In experiment 1, PRRS virus was detected in mammary gland secretions of both vaccinated and 1 of 2 virus-inoculated sows. In experiment 2, virus was not detected in samples from either vaccinated sow. In experiment 3, all samples yielded negative results. CONCLUSIONS AND CLINICAL RELEVANCE: Naïve sows inoculated late in gestation shed PRRS virus in mammary secretions. Previous vaccination appeared to prevent shedding during the subsequent lactation. Results for samples obtained from sows in commercial herds suggested that virus shedding in mammary gland secretions of such sows is uncommon.

Transurethral microwave thermotherapy for symptomatic benign prostatic hyperplasia: short-term experience with Prostcare.

PURPOSE: To assess our short-term experience with transurethral microwave thermotherapy (TUMT) for symptomatic benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: From August 1993 through July 1994, in total 65 patients with symptomatic BPH were enrolled into this study. The patients' ages ranged from 56 to 95 years with a mean of 70 years. Under local anesthesia with intraurethral instillation of Xylocaine jelly only, all patients received one session of TUMT for up to 60 min with Prostcare equipment. Uroflowmetry was performed and international prostatic symptom score (IPSS) determined before 3 and 6 months after TUMT for assessment of efficacy. All adverse events were recorded and evaluated for clinical relevance. RESULTS: At 3 and 6 months following TUMT, the mean IPSS decreased from 19.7 +/- 6.8 (baseline) to 12.8 +/- 8.2 (-46%) and to 15.5 +/- 9.0 (-21%), respectively; the maximal urine flow rate at 3 and 6 months increased from 9.1 +/- 4.8 ml/s (baseline) to 11.0 +/- 4.9 ml/s (+21%) and to 10.9 +/- 5.6 ml/s (+19%), respectively. During TUMT, burning sensation was the most frequent complaint (38.5%), followed by urethral discomfort (29.2%) and urgency (9.2%). Two patients (3.1%) interrupted TUMT, because of intolerable pain. Following TUMT micturition pain (73.8%) and gross hematuria (45.9%) were the most adverse events. Most of these adverse events disappeared within 2 weeks. One patient suffered from skin erosion over the penoscrotal junction 1 week later. None had retrograde ejaculation; 1 patient complained of erectile dysfunction. CONCLUSION: Although the efficacy of TUMT with Prostcare became less prominent 6 months after TUMT, TUMT was still a tolerable, safe alternative treatment of BPH, especially in patients who were not suitable for transurethral resection of the prostate or anesthesia.

Induction of apoptosis and down-regulation of bcl-6 in mutu I cells treated with ethanolic extracts of the Chinese herbal supplement PC-SPES.

PC-SPES, an HPLC-standardized 8-herb dietary supplement prepared by proprietary extraction/mixing technologies, appears to have a number of health benefits when given to cancer patients. These include reduction of serum PSA (prostate specific antigen) in individuals diagnosed with advanced prostate carcinoma, and overall improvement of morbidity and immune status in terminal cancer cases. Since the expression of bcl-6 in T and B lymphocytes has been reported to be significantly down regulated by mitogens, we reason that the immune boosting effects of PC-SPES could involve the modulation of bcl-6 expression. Such a hypothesis was tested in the bcl-6 abundant Mutu I cells. Specifically, we investigated the effects of PC-SPES in regulating cell growth, induction of apoptosis, effecting changes in the retinoblastoma gene RB and the modulation of expression of the bcl-6. Herein we report that proliferation of Mutu I cells was inhibited by a 3-7 day incubation with ethanolic extracts of PC-SPES, with concurrent induction of apoptosis. In addition, a dose-dependent reduction of bcl-6 was observed, with no concomitant change in either the phosphorylated or the unphosphorylated forms of RB. These data raise the possibility that PC-SPES may enhance immune functions in vivo by down-regulating bcl-6 expression. Alternatively, decrease in bcl-6 could serve as a biomarker for testing the efficaciousness of PC-SPES in vivo.

Cloning and functional expression of B chains of beta-bungarotoxins from Bungarus multicinctus (Taiwan banded krait).

The cDNA species encoding the B chains (B1 and B2) of beta-bungarotoxins (beta-Bgt) were constructed from the cellular RNA isolated from the venom glands of Bungarus multicinctus (Taiwan banded krait). The deduced amino acid sequences of the B chains were different from those determined previously by a protein sequencing technique. One additional Arg residue is inserted between Val-19 and Arg-20 of the B1 chain. Similarly the insertion of one additional Val residue between Val-19 and Arg-20 of the B2 chain is noted. Thus the B chains should comprise 61 amino acid residues. Moreover, the residues at positions 44-46 are Gly-Asn-His, in contrast with a previous result showing the sequence His-Gly-Asn. Instead of Asp, the residues at positions 41 and 43 are Asn. The B chain was subcloned into the expression vector pET-32a(+) and transformed into Escherichia coli strain BL21(DE3). The recombinant B chain was expressed as a fusion protein and purified on a His-Bind resin column. The yield of affinity-purified fusion protein was increased markedly by replacing Cys-55 of the B chain with Ser. However, the isolated B(C55S) chain became insoluble in aqueous solution after removal of the fused protein from the affinity-purified product, suggesting that protein-protein interactions might be crucial for stabilizing the structure of the B chain. The B(C55S) chain fusion protein showed activity in blocking the voltage-dependent K+ channel, but did not inhibit the binding of beta-Bgt to synaptosomal membranes. These results, together with the finding that modification of His-48 of the A chain of beta-Bgt caused a marked decrease in the ability to bind toxin to its acceptor proteins, suggest that the B chain is involved in the K+ channel blocking action observed with beta-Bgt, and that the binding of beta-Bgt to neuronal receptors is not heavily dependent on the B chain.

Involvement of tyrosine phosphorylation of p185(c-erbB2/neu) in tumorigenicity induced by X-rays and the neu oncogene in human breast epithelial cells.

Ionizing radiation is the exogenous agent best proven to induce breast cancer. c-erbB2/neu amplification and overexpression are known to occur in breast cancer and are correlated with aggressive tumor growth and poor prognosis. We have developed simian virus 40-immortalized cell lines from normal human breast epithelial cells (HBECs) with luminal and stem-cell characteristics. In this study, we examined whether x-rays and a mutated neu oncogene are capable of inducing tumorigenicity in these cells. The results indicated that x-rays were effective in converting immortal non-tumorigenic HBECs to weakly tumorigenic cells that then could be transformed to highly tumorigenic cells by the neu oncogene. The in vitro growth of these tumorigenic cells was significantly faster than that of the parental non-tumorigenic cells in growth factor- and hormone-supplemented or -depleted media. The neu oncogene, however, had no tumorigenic effect on immortal non-tumorigenic cells. The expression of p185(c-erb82/neu) was elevated in neu-transduced immortal or weakly tumorigenic cell lines. However, only in the latter was p185(c-erbB2/neu) found to be phosphorylated at tyrosine residues. Thus, x-rays appear to induce a genetic alteration that confers weak tumorigenicity on immortal HBECs and interacts with p185(c-erbB2/neu) directly or indirectly to give rise to fast-growing tumors.

Chinese herb constituent beta-eudesmol alleviated the electroshock seizures in mice and electrographic seizures in rat hippocampal slices.

We have found that beta-eudesmol, a sesquiterpenol constituent of Chinese herb antagonized organophosphate-induced lethal toxicity by reversing the neuromuscular failure and reducing the occurrence of convulsions. Its possible antiepileptic action was further explored in electroshock seizure mice in vivo and in high potassium treated rat hippocampal slices in vitro. At a dose with little effect on the motor activity, beta-eudesmol prevented the convulsions and lethality induced by maximal electroshock but not those by pentylenetetrazol or picrotoxin. At subeffective doses, beta-eudesmol and phenytoin showed additive effect in preventing electroshock seizures. Extracellular recording of field potentials in CA1 pyramidal layer of hippocampal slices showed that beta-eudesmol reduced the high potassium (8.5 microM)-induced electrographic seizure activity. The potential of beta-eudesmol to serve as an antiepileptic or a conjuvant in phenytoin therapy is suggested.

Chromosomal translocations cause deregulated BCL6 expression by promoter substitution in B cell lymphoma.

The BCL6 gene codes for a zinc-finger transcription factor and is involved in chromosomal rearrangements in 30-40% of diffuse large-cell lymphoma (DLCL). These rearrangements cluster within the 5' regulatory region of BCL6 spanning its first non-coding exon. To determine the functional consequences of these alterations, we have analyzed the structure of the rearranged BCL6 alleles and their corresponding RNA and protein species in two DLCL biopsies and one tumor cell line which carried the t(3;14)(q27;q32) translocation involving the BCL6 and immunoglobulin heavy-chain (IgH) loci. In all three cases, the breakpoints were mapped within the IgH switch region and the BCL6 first intron, leading to the juxtaposition of part of the IgH locus upstream and in the same transcriptional orientation to the BCL6 coding exons. An analysis of cDNA clones showed that these recombinations generate chimeric IgH-BCL6 transcripts which initiated from IgH germline transcript promoters (I mu or I gamma 3), but retain a normal BCL6 coding domain. In the tumor cell line, the chimeric I gamma 3-BCL6 allele, but not the germline BCL6 gene, was transcriptionally active and produced a normal BCL6 protein. These findings indicate that t(3;14) translocations alter BCL6 expression by promoter substitution and imply that the consequence of these alterations is the deregulated expression of a normal BCL6 protein.

Silicon and silicone: theoretical and clinical implications of breast implants.

In the past 10 years, there have been multiple published reports associating silicone breast implants with scleroderma, morphea, SLE, rheumatoid arthritis, CREST syndrome and "human adjuvant disease." The alleged offending material, silicone, is a synthetic polymer containing a silicon-oxygen backbone. Beginning with the heating of SiO2 in the presence of carbon, elemental silicon is produced. Methylchloride is added and the resulting product is hydrolyzed to form low molecular weight prepolymers which are linked to form linear silicone polymers and cross-linked to yield silicone rubbers or elastomers. The polymeric and hydrophobic characteristics of silicone and the presence of electrostatic charges and organic sidegroups make silicone a potentially ideal immunogen, leading to cross-reactivity with autoantigens. Silicon is an essential constituent of proteoglycans which theoretically could result in immunological cross-reactions between silicone and connective tissues. Although the literature contains numerous examples of silicone-associated autoimmune disease, there is no consistent pattern of immunological abnormalities observed. There are, however, some intriguing and interesting observations. Further large-scale studies are needed to determine if a link between silicone exposure and autoimmunity exists. Also, since the inducing events of autoimmune diseases are unknown, studies on silicone could provide a model for autoimmune diseases associated with toxicological factors.

Suppression of growth by dietary fish oil of human breast carcinomas maintained in three different strains of immune-deficient mice.

It has been reported that high levels of dietary fish (menhaden) oil, compared with corn oil, suppress the growth of MDA-MB231 and MCF-7 human breast carcinomas maintained in female athymic nude (T lymphocyte-deficient) mice. The purpose of this study was to determine whether dietary fish (menhaden) oil, compared with corn oil, can also suppress the growth of these carcinomas when maintained in female beige-XID-athymic nude (T lymphocyte- and NK/LAK cell-deficient) mice and in female severe combined immune-deficient (SCID) mice (total lack of functional T and B lymphocytes). Results clearly show that dietary fish (menhaden) oil can significantly (p < 0.05) suppress the growth of these carcinomas in the beige-XID-athymic nude mouse and the SCID mouse. Such results provide evidence that the growth suppression of MDA-MB231 and MCF-7 human breast carcinomas, induced by dietary fish oil, is not mediated by immune system mechanisms involving T lymphocytes, B lymphocytes, and/or NK/LAK cells.

Inhibition of Moloney murine leukemia virus reverse transcriptase activity by tetrahydroxyxanthones isolated from the Chinese herb, Tripterospermum lanceolatum (Hyata).

Five tetrahydroxyxanthones (THXs) isolated from Tripterospermum lanceolatum (Hyata) have been shown to have a strong inhibitory effect on Moloney murine leukemia virus reverse transcriptase (Mo-MLV RT) activity when (rA)n-(dT)15 and (rC)n-(dT)12-18 were used as template-primers. 50% inhibitory concentrations of 1,3,5,6-THX, 2,3,6,7-THX 1,3,6,7-THX, 3,4,5,6-THX, and 3,4,6,7-THX were determined to be 0.15, 0.27, 0.58, 0.12, and 0.12 microM, respectively. Their effects were concentration-dependent, and the mode of inhibition was found to be by competitive inhibition with respect to template-primer. The tetrahydroxyl groups of THXs were shown to be important for their inhibitory activity. Acylation of THXs with various groups resulted in a moderate or strong decrease in their inhibitory activity.