Efficacy of transfer factor in treating patients with recurrent ocular herpes infections

Recurrent ocular herpes is an insoluble problem for the clinician. As cellular immunity plays an important role in controlling herpes relapses, and other studies have shown the efficacy of HSV-specific transfer factor (TF) for the treatment of herpes patients, an open clinical trial was undertaken in 134 patients (71 keratitis, 29 kerato-uveitis, 34 uveitis) suffering from recurrent ocular herpetic infections. The mean duration of the treatment was 358 days, and the entire follow-up period 189121 before, and 64062 days after TF treatment. The cell-mediated immune response to the viral antigens, evaluated by the lymphocyte stimulation test (LST) and the leucocyte migration test (LMT) (P<0.001), was significantly increased by the TF treatment. The total number of relapses was decreased significantly during/after TF treatment, dropping from 832 before, to 89 after treatment, whereas the cumulative relapse index (RI) dropped, during the same period, from 13.2 to 4.17 (P<0.0001). No side effects were observed. It is concluded that patients with relapsing ocular herpes can benefit from treatment with HSV-specific TF.     

Hybridomas in a bioreactor cascade: modeling and determination of growth and death kinetics

Hybridomas were cultured under steady-state conditions in a series of two continuous stirred-tank reactors (CSTRs), using a serum-free medium. The substrate not completely converted in the first CSTR, was transported with the cells to the second one and very low growth rates, high death rates, and lysis of viable cells were observed in this second CSTR. These conditions are hardly accessible in a single vessel, because such experiments would be extremely time-consuming and unstable due to a low viability. In contrast to what is often observed in literature, kinetic parameters could thus be derived without the neccessity for extrapolation to lower growth rates. Good agreement with literature averages for other hybridomas was found. Furthermore, showing that the reactor series is a valuable research tool for kinetic studies under extreme conditions, the possibility to observe cell death under stable and defined steady-state conditions offers interesting opportunities to investigate apoptosis and necrosis. Additionally, a model was developed that describes hybridoma growth and monoclonal antibody production in the bioreactor cascade on the basis of glutamine metabolism. Good agreement between the model and the experiments was found.Abbreviation MAb Monoclonal antibody Nomenclature C _AConcentration of any (mol m^-3) component A D Dilution rate (s^-1) K _dDeath-rate constant (mol m^-3) K _lLysis-rate constant (mol m^-3) K _sMonod constant (mol m^-3) m Maintenance coefficient (mol cell^-1 s^-1) q Specific consumption (mol cell^-1 s^-1) or production rate t Time (s) X Cell concentration (cell m^-3) Y Yield coefficient (cell mol^-1) Greek symbols _d Specific death rate (s^-1) _l Specific lysis rate (s^-1) of viable cells _net Net specific growth (s^-1) rate _true True specific growth (s^-1) rate     

Polypores new to Japan 1. Species ofPolyporus,with a note onP. hartmanni

Polyporus admirabilis, P. dictyopus, P. guianensis, P. pseudobetulinus, P. tubaeformis andP. udus are reported for Japan for the first time.Polyporus tubaeformis had been confused withP. melanopus, but the Japanese collections were conspecific with Norwegian isolates ofP. tubaeformis. A key to allPolyporus species in Japan is provided.Polyporus hartmanni is reported for the first time outside the Australian continent. As the species has a bipolar heterothallism and produces brown rot, its taxonomic relationship withPolyporus s. str. is discussed.The Japanese Science and Technology Agency (STA) is thanked by the authors for financial support.     

Transfer of heavy metals from sediment to fish,and their biliary excretion

Uptake and biliary excretion of metals were studied in rainbow trout, Oncorhynchus mykiss, exposed through spiked sediment to a mixture of seven heavy metals. Metal concentrations and toxicity of bile and blood plasma were used as indicators of exposure. Among the seven metals (Cd, Cr, Cu, Hg, Ni, Pb, and Zn) only three (Cu, Hg, and Pb) were concentrated in the bile (bile-plasma ratio >1). Bile-plasma ratios in the rainbow trout were similar to those found in rats for Cu and Hg. Daphnia magna bioassays were used to determine toxicity of bile and blood plasma in the same trout. Toxicity of bile and blood plasma increased after treatment with acid. An analysis of variance (ANOVA) showed that toxicity of bile and blood plasma to D. magna in metal-exposed trout was significantly correlated with (1) bile and blood plasma test concentration, (2) acid treatment of bile and blood plasma (hydrolysis of metal-plasma and metal-bile complexes) and (3) sediment concentration of metals during exposure of trout. In order to significantly detect the magnitude of the exposure to a xenobiotic the biomarker must respond in a dose- or time-dependent manner. Therefore, the potential use of bile toxicity as a biomarker of heavy metal exposure in fish is probably limited by the low bioconcentration of many of these toxicants in bile.     

The role of glutamate in swim initiation in the medicinal leech

Antagonists were used to investigate the role of the excitatory amino acid,l-glutamate, in the swim motor program ofHirudo medicinalis. In previous experiments, focal application ofl-glutamate or its non-NMDA agonists onto either the segmental swim-gating interneuron (cell 204) or the serotonergic Retzius cell resulted in prolonged excitation of the two cells and often in fictive swimming. Since brief stimulation of the subesophageal trigger interneuron (cell Tr1) evoked a similar response, we investigated the role of glutamate at these synapses. Kynurenic acid and two non-NMDA antagonists, 6,7-dinitroquinoxaline-2,3-dione (DNQX) and Joro spider toxin, effectively suppressed (1) the sustained activation of cell 204 and the Retzius cell following cell Tr1 stimulation and (2) the monosynaptic connection from cell Tr1 to cell 204 and the Retzius cell, but did not block spontaneous or DP nerve-activated swimming. Other glutamate blockers, including -d-glutamylaminomethyl sulfonic acid,l(+)-2-amino-3-phosphonoproprionic acid and 2-amino-5-phosphonopentanoic acid, were ineffective. DNQX also blocked both indirect excitation of cell 204 and direct depolarization of cell Tr1 in response to mechanosensory P cell stimulation. Our findings show the involvement of non-NMDA receptors in activating the swim motor program at two levels: (1) P cell input to cell Tr1 and (2) cell Tr1 input to cell 204, and reveal an essential role for glutamate in swim initiation via the cell Tr1 pathway.     

The nervous system of Tricladida. I. Neuroanatomy ofProcerodes littoralis (Maricola,Procerodidae): An immunocytochemical study

The organization of the nervous system ofProcerodes littoralis (Tricladida, Maricola, Procerodidae) was studied by immunocytochemistry, using antibodies to authentic flatworm neuropeptide F (NPF) (Moniezia expansa). Compared to earlier investigations of the neuroanatomy of tricladid flatworms, the pattern of NPF immunoreactivity inProcerodes littoralis reveals differences in the following respects: 1. Shape and structure of the brain. 2. Number and composition of longitudinal nerve cords. 3. Shape of branches of, and transverse connections between, main ventral nerve cords. 4. Composition of the pharyngeal nervous system. The rich innervation by NPF immunoreactive (IR) fibres and cells of the subepithelial muscle layer, the pharynx musculature and the musculature of the male copulatory apparatus indicates a neurotransmitter or neuromodulatory influence on muscular activity.     

Net Uptake of Sulfate and its Transport to the Shoot in Spinach Plants Fumigated with H2S or SO2: Does Atmospheric Sulfur Affect the “Inter-Organ” Regulation of Sulfur Nutrition?*

Spinach plants (Spinacea oleracea L. cv. Estivato) were grown on nutrient solutions under deficient, normal and excess sulfate supply. In both young and mature plants net uptake of sulfate and its transport to the shoot increased with increasing sulfate supply, but both processes proceeded at a higher rate in young as compared to mature plants. The relative sulfate transport, i.e. the relative amount of the sulfate taken up that is transported to the shoot, decreased with increasing sulfate supply. Apparently, net uptake of sulfate is not strictly controlled by the sulfur demand of the shoot, but xylem loading appears to counteract excess transport of sulfate to the shoot. Fumigation with H₂S or SO₂ reduced net uptake of sulfate by the roots in sulfur-deficient plants and absolute as well as relative sulfate transport to the shoot independent of the three sulfate levels supplied to the plant. At the same time thiol contents of the shoot and the root were enhanced by fumigation with H₂S and SO₂. These findings are consistent with the idea that thiols produced in the leaves can mediate demand-driven control of sulfate uptake by the roots and its transport to the shoot.     

Preliminary evidence of endotoxic activity of Bilophila wadsworthia

In this study we describe two properties of the Gram-negative bacterium Bilophila wadsworthia, namely the ability to clot Limulus lysate and the capacity to induce the production of tissue factor-like procoagulant activity by human mononuclear cells in vitro. Although exhibited at a lower degree when compared with those of typical Gram-negative bacteria or Gram-negative endotoxin those activities may account in part for Bilophila's pathogenicity. The capacity indeed to induce fibrin formation through the interaction with mononuclear cells suggests one mechanism by which the microorganism might cause abscess formation in the host. Moreover, since this activity is dependent on the number of Bilophila interacting with mononuclear cells, we hypothesize that this biological activity is closely influenced by growth environment.