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The Higashino Beach of Karatsu Coast in Japan has been prone to erosion since 2013. As a part of the coastal protection, regular monitoring of the beach’s topography plays an important role to determine the factors influencing the changing of beach topography. The elevation of 10 certain points was measured on a selected cross-shore profile. The monitoring was carried out every month in the winter was characterized by high waves and every two months in the summer was characterized by low waves. The wave height of extreme wave events and sediment budget of the Higashino Beach were taken into account for evaluating the changing of the beach topography. The monitoring results showed that the beach was eroded in the cases of the extreme wave events with wave height exceeding 3m and accreted in the other cases. The wave data analysis showed that the magnitude and frequency of the extreme wave events with the wave height over 3m in a year has been increased since 2011. The dominant wave directions in the Karatsu Coast are N and NNE that cause the longshore sediment transport from the east to the Higashino Beach. However, the annual sediment discharge from Tamashima River has been decreased since 1993. In addition, the long shore sediment transport rate was reduced due to the construction of detached breakwater on the east of Karatsu Coast. It can be concluded that the erosion in the Higashino Beach caused by increment of the magnitude and frequency of the extreme wave events and the reduction of sediment discharge from the Tamashima River. It was also found that the number of the extreme wave events with the wave height exceeding 3m should be taken into account for evaluating the long term variation of the beach topography in the Higashino Beach.

This paper presents an example of sediment infill evaluation of navigation channel during dredging work. Matarbari Ultra Super Critical Coal-Fired power project, which includes the dredging of a 14 km long navigation channel, is currently in progress on the southeast part of Bangladesh. Due to high-turbid water on the coastal area of Bangladesh, it is concerned that the dredging volume might be extremely large. To evaluate the sedimentation of the channel before starting the work, this study investigates the characteristics of the physical systems in the project area based on data collection of wave, tidal currents, seabed materials, etc. The simulation model was developed and validated by comparing with bathymetry survey result. The validated numerical model was then applied to estimate the sedimentation volume in 3 years after the future channel dredging works. Numerical tests clarified that additional dredging volume increases due to the delay on the construction schedule of the sedimentation control bund.

The aim of this study was to describe outcomes of laparoscopic living donor right nephrectomy (LLDRN) and study factors affecting the length of right renal vein from the donors.This study was conducted in 60 donors (48 males and 12 females) from January 2016 to December 2017. We performed a retrospective review of consecutive patients who underwent transperitoneal right laparoscopic living donor nephrectomy at our unit.LLDRN was successfully performed in all subjects by the same surgeons. Among 60 cases, 47 donors had single renal artery and vein, 2 cases had one artery and 2 veins, and 5 donors had 2 arteries and one vein, and the rest had 2-3 arteries with 1-3 veins. Operative time was 142.60±33.73min. Warm ischemic time was 2.64±0.76min. The mean hospital stay was 6.69±0.63 days. The median length of right renal vein was 1.92±0.41cm. All transplanted kidneys showed immediate function. No graft losses were recorded. Almost no gender differences were found in study variables except BMI and warm ischemic time, that was higher BMI but shorter warm ischemic time in female versus male donors. Further analysis showed a negative correlation between BMI and right renal vein (r=-0.282, P0.05), but a positive correlation between operative time and estimate blood loss (r=0.37, P0.01).LLDRN is a feasible safe procedure, less traumatic approach, and provides good outcomes kidney for recipients. Notably, in the study group the higher BMI was associated with resulting more difficult LLDRN and kidney transplantation.

The objective of this work is to develop a data processing system that can automatically generate waypoints for navigation of an unmanned aerial vehicle (UAV) to inspect surfaces of structures like buildings and bridges. The input includes data recorded by two 2D laser scanners, orthogonally mounted on the UAV, and an inertial measurement unit (IMU). To achieve the goal, algorithms are developed to process the data collected. They are separated into three major groups: (i) the data registration and filtering to generate a 3D model of the structure and control the density of point clouds for data completeness enhancement; (ii) the surface and obstacle detection to assist the UAV in monitoring tasks; and (iii) the waypoint generation to set the flight path. Experiments on different data sets show that the developed system is able to reconstruct a 3D point cloud of the structure, extract its surfaces and objects, and generate waypoints for the UAV to accomplish inspection tasks., In The 14th International Conference on Control, Automation, Robotics and Vision, ICARCV 2016

A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-cyclic carbazate analogues was prepared and evaluated for antibacterial activity. These 2,3-anhydro macrolides were found to be potent antibacterial agents in vitro against macrolide-susceptible organisms including Staphylococcus aureus 6538P, Streptococcus pyogenes EES61, and Streptococcuspneumoniae ATCC6303. These compounds were also very active against some organisms that show macrolide resistance (S. aureus A5177, S. pyogenes PIU2584, and S. pneumoniae 5649). The compounds generally showed poor activity against organisms with constitutive MLS resistance. Selected compounds were evaluated in vivo in mouse protection studies. Although most of the compounds tested in vivo showed poor efficacy, two compounds, 38 and 57, were more active than clarithromycin against S. pneumoniae ATCC6303.

Macrolides, such as clarithromycin and azithromycin, having good activity against pathogens such as Legionella, Chlamydia, Campylobacter spp, Branhamella spp, Pasteurella multocida and streptococci, have gained wide acceptance for the treatment of both upper and lower respiratory tracts, as well as cutaneous infections. Emergence of bacterial resistance, particularly in gram-positive bacteria, has been observed. Macrolide-resistant Streptococcus pneumoniae and S. pyogenes are found in France and many other countries, resulting in failure of therapy for pneumonia, pharyngitis, and skin infection. RU 004, HMR 3647, and TE 802 were reported to be active against these resistant strains. Research at Abbott produced several macrolide derivatives in the anhydrolide, tricyclic and tetracyclic ketolides as well as 6-O-alkyl ketolides series having potent activity against macrolide resistant S. pyogenes and S. pneumoniae. Research on streptogramins to overcome bacterial resistance in gram-positive bacteria has produced interesting compounds. Another class of antibacterial agent called quinolones is useful for the treatment of bacterial infections of respiratory tract, urinary tract, skin and soft tissues, as well as sexually transmitted diseases. Ciprofloxacin, the market leader, however, has low potency against anaerobes. Bacterial resistance ( such as Pseudomonas aeruginosa and methicillin- resistant Staphylococcus aureus ) to ciprofloxacin is increasing rapidly. Many quinolone compounds are being synthesized to address these drawbacks. The new quinolones currently under development are characterized by enhanced activities against streptococci, staphylococci, enterococci, and anaerobes. This presentation reviews the current research in the identification of agents to overcome the macrolide and quinolone resistance.

The 11,12-cyclic carbazate of 3-keto-6-O-methylerythromycin A (4) was prepared. This compound shows in vitro antibacterial activity comparable to erythromycin A (1) against erythromycin-susceptible organisms and increased activity against some erythromycin-resistant organisms. Using 4 as a lead, a series of analogues was prepared by acylation or alkylation of the carbazate nitrogen. Several of the N-alkylated derivatives showed dramatically improved antibacterial activity against both susceptible and resistant organisms as compared to erythromycin A.

A-84441, a potent new antitumor quinolone, was active in vitro and in vivo against murine and human tumors. A-84441, a prodrug, was comparable in potency to the parent compound with an IC50 range of 0.03-0.49 microgram/ml against a panel of murine and human tumor cell lines. The parent compound bound mammalian DNA in a magnesium-dependent manner and caused inhibition of DNA and RNA synthesis. A-84441 produced a significant increased life span and cures in three lines of i.p. implanted murine tumors. A-84441 was active against seven of nine solid tumors including s.c. murine tumors and human tumor xenografts. The compound appeared to be more active when administered i.v. compared to i.p. injection. Antitumor efficacy was little effected by treatment schedule, although multiple divided dosing was generally more effective than single dose treatment. A-84441 was over 10-fold-more active against murine leukemic cells than against normal murine bone marrow cells. The acute toxicity of A-84441 following single or multiple dosing ranged between 11 and 50 mg/kg dependent on schedule of administration when given by i.v. or i.p. route. The agent had no apparent toxicity or efficacy when administered p.o.

Glucose metabolism was evaluated in transgenic mice expressing the human GLUT 4 glucose transporter. Fed GLUT 4 transgenic mice exhibited a 32% and 56% reduction in serum glucose and insulin and a 69% and 33% increase in non-esterified fatty acid and lactate levels, respectively. Transgenic mice exhibited a significant increase in whole-body glucose disposal during a euglycaemic-hyperinsulinaemic clamp. Insulin-stimulated glucose uptake in isolated soleus muscles and adipocytes was greater in transgenic compared to control mice due to increased basal glucose uptake. Transgenic mice displayed increased glycogen levels in liver and gastrocnemius muscle, and increased insulin-stimulated 14C-glycogen accumulation in isolated soleus muscle. We conclude that over-expression of the GLUT 4 glucose transporter in mice results in 1) an increase in whole-body glucose disposal and storage, and 2) an increase in both basal and insulin-stimulated glucose uptake and disposal in vitro. These changes resulted in the reduction of serum glucose and insulin levels. These results provide direct evidence that glucose transport (and GLUT 4 per se) plays a significant role in regulating whole-body glucose homeostasis. Additionally, these data support the idea that pharmacological strategies directed at increasing the expression of GLUT 4 protein may have beneficial (hypoglycaemic) effects in the diabetic state.

The in vitro induction of LAK cell activity was studied in cancer and AIDS patients. F3, an immuno-regulatory component of Astragalus membranaceus was shown capable of potentiating the LAK cell inducing activity of rIL-2. The killing activity against Hs294T melanoma cell line of LAK cells induced by 50 U/ml rIL-2 in the presence of F3 (55 micrograms/ml) reached 64% which was comparable to that (60%) induced by 500 u/ml of rIL-2 alone. With F3 plus rIL-2, the effector to target cell ratio could be reduced to one-half in order to obtain an equivalent level of cytotoxicity when rIL-2 was used alone. In some patients, whose peripheral blood lymphocytes were relatively inert to rIL-2, F3 could make them responsive to rIL-2. These results imply that F3 may be useful to potentiate LAK cell activity, reduce the amount of rIL-2 and thus minimize the later's toxic side effects when used in vivo.

DNA topoisomerases, found in all prokaryotic and eukaryotic cells, play a key role in controlling the topological state of DNA. They are involved in DNA replication, RNA transcription and recombination affecting cell proliferation. Quinolone antibacterial agents have been shown to be inhibitors of DNA gyrase, a bacterial topoisomerase II enzyme. The eukaryotic topoisomerase II is the target of various cytotoxic agents such as adriamycin and etoposide. Due to the mechanistic similarities and sequence homologies shared by both bacterial and mammalian DNA topoisomerase II, we initiated a screening programme to search for quinolones as antitumour agents and reported the identification of a new class of quinolone, quinobenoxazines, having excellent in vitro cytotoxic activity comparable to adriamycin. In the continuation of this research work, we synthesized a series of amino-substituted quinobenoxazines and found that some of them possess more potent in vitro cytotoxicity than the parent unsubstituted quinobenoxazines. The chemical synthesis as well as biological properties of these tetracyclic quinolones are described.

The inhibitory effect of 44 quinolone antibacterials and derivatives (common structure, 4-oxoquinoline-3-carboxylic acid) on cytochrome P450 isoform CYP1A2 activity was tested using human liver microsomes and caffeine 3-demethylation as a specific test system for this enzyme. By direct comparison of molecules differing structurally in only one position, the following structure-activity relationships were found. 3'-Oxo derivatives had a reduced or similar activity and M1 metabolites (cleavage of piperazinyl substituent) had a greater inhibitory activity, compared with the parent molecule. Alkylation of the 7-piperazinyl substituent resulted in a reduced inhibitory potency. Naphthyridines with an unsubstituted piperazinyl group at position 7 displayed a greater inhibitory potency than did corresponding quinoline derivatives. Derivatives with a fluorine substitution at position 8 had only a minor effect. Molecular modeling studies with inhibitors and caffeine showed that it is possible to explain the potency of the quinolones to inhibit CYP1A2 on a molecular level. The keto group, the carboxylate group, and the core nitrogen at position 1 are likely to be the most important groups for binding to the active site of CYP1A2, because the molecular electrostatic potential of all inhibitors is very similar to that of caffeine in these regions. The presence of a piperazinyl substituent, however, seems to be no prerequisite for inhibitory potency. Finally, an equation to estimate the potency to inhibit CYP1A2 was developed by quantitative structure-activity relationship analysis.

DNA topoisomerases, found in all prokaryotic and eukaryotic cells, play a key role in controlling the topological state of DNA. Quinolone antibacterial agents have been shown to be inhibitors of DNA gyrase, a bacterial topoisomerase II enzyme. The eukaryotic topoisomerase II is the target of various cytotoxic agents such as adriamycin and etoposide. Recently, several quinolones having C-8 fluoro and C-8 chloro substituents have been found to have cytotoxic activities and to interact with mammalian topoisomerase II. In searching for an antitumour agent of the quinolone class, we identified several quinolones having excellent in vitro cytotoxic activity. A-74932 also possesses good activity in vivo against both systemic tumour and subcutaneously implanted murine solid tumours as well as human tumour xenografts. The chemical synthesis as well as biological properties of A-74932 are described.

14559 Background: Bevacizumab, a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF), is widely used in the treatment of many solid tumors. Many clinical studies ...

Very little is known about the structure-activity relationship of quinolone antibacterials at the 2-position. Because of the loss of biological activity with 2-methyl and 2-hydroxyl substitution, modifications at C-2 were generally considered to be unfavourable. Quinolone derivatives having a ring between positions 1 and 2 were recently shown to have biological activity. The sulfur-bridged analogs such as the benzothiazolo[3,2-a]quinolone, KB-5246 and NAD-394 have been reported to be highly active in vitro. The authors have synthesized 2-methylthiociprofloxacin, 2-methylofloxacin, the 5-oxopyrrolo[1,2-a]quinoline and isothiazolonaphthyridine to assess the importance of the sulfur atom on biological activity as well as the effect of C-2 substituent on the spatial arrangements of N-1 or the 3-carboxylic group. It was found that the planarity between the 4-keto and 3-carboxylic acid groups of quinoline molecules is the most important criterion for biological activity. The syntheses of the above four compounds are also described.

Tosufloxacin (5, A-61827 tosylate or T-3262) is currently under product development by both Abbott Laboratories and Toyama Chemical Co. Its registration as antibacterial agent has been approved in Japan. It has been found to be extremely effective in treating several bacterial infections. However, due to its inherent low water solubility, the development of an intravenous formulation will be extremely difficult and may preclude its parenteral use. In search of a more water-soluble analog of tosufloxacin for parenteral use, the 3-formyl derivative of tosulfoxacin, A-71497 (13), was synthesized for evaluation. It was found to produce high plasma levels of tosufloxacin upon both oral and subcutaneous administration to mice. High plasma levels of tosufloxacin were also obtained when 13 was administered both orally and intravenously to dogs. It possesses increased water solubility and makes the development of intravenous formulation possible. The chemical synthesis as well as biological properties of A-71497 (13) are described.

The effects of hypothyroidism on glycogen metabolism in rat skeletal muscle were studied using the perfused rat hindlimb preparation. Three weeks after propylthiouracil treatment, serum thyroxine was undetectable and muscle glycogen and Glc-6-P were decreased. Basal and epinephrine-stimulated phosphorylase a and phosphorylase b kinase activities were also significantly reduced, as were epinephrine-stimulated cAMP accumulation and cAMP-dependent protein kinase activity. Conversely, basal and epinephrine-stimulated glycogen synthase I activities were significantly higher while the Ka of the enzyme for Glc-6-P was lower in hypothyroid animals. Propylthiouracil-treated rats also had increased phosphoprotein phosphatase activities towards phosphorylase and glycogen synthase and decreased activity of phosphatase inhibitor 1. beta-Adrenergic receptor binding and basal and epinephrine-stimulated adenylate cyclase activities were reduced in muscle particulate fractions from hypothyroid rats. Administration of triiodothyronine to rats for 3 days after 3 weeks of propylthiouracil treatment restored the altered metabolic parameters to normal. It is proposed that the decreased beta-adrenergic responsiveness of the enzymes of glycogen metabolism in hypothyroid rat skeletal muscle is due to increased activity of phosphoprotein phosphatases and to reduced beta-adrenergic receptors and adenylate cyclase activity.

The effect of the tumor promoter phorbol 12-myristate 13-acetate (PMA) on expression of the P-enolpyruvate carboxykinase gene was studied in rat hepatoma H4IIE cells. Like insulin, PMA provokes a concentration and time-dependent decrease of mRNA coding for that enzyme that is due to an inhibition of P-enolpyruvate carboxykinase gene transcription. This effect of PMA is rapid, reversible, specific for phorbol esters known to be active in other systems, and it does not require on-going protein synthesis. PMA overrides the stimulatory effects cAMP and glucocorticoid analogs have on the transcription of this gene. A synthetic diacylglycerol, sn-1,2-dioctanoylglycerol, also inhibits P-enolpyruvate carboxykinase gene transcription. These effects of PMA and synthetic diacylglycerol are specific, since neither affected total mRNA synthesis. We conclude that diacylglycerol and phorbol esters, specific stimulators of protein kinase C, inhibit the transcription of P-enolpyruvate carboxykinase gene in H4IIE cells. The findings support the hypothesis that diacylglycerols generated in the plasma membrane can act as an intracellular signal that regulates specific gene expression.

Perfused hindlimb muscle from fed adrenalectomized rats accumulated more 2-deoxyglucose at submaximal concentrations of insulin in comparison to muscle from fed normal rats. However, in the fasted state, insulin-stimulated 2-deoxyglucose uptake was largely inhibited by adrenalectomy. Basal 2-deoxyglucose uptake did not differ between fed and fasted normal or adrenalectomized rats. The changes in insulin effects caused by adrenalectomy were due to altered hexose transport as shown by measurements of 3-O-methylglucose uptake and of intracellular free and phosphorylated 2-deoxyglucose. Muscles of fasted normal and fed or fasted adrenalectomized rats showed higher basal glycogen synthase --glucose-6-P/+glucose-6-P activity ratios than those of fed normal rats probably because of decreased glycogen content. However, muscles from fed or fasted adrenalectomized rats did not show any alterations in insulin effects on the activity ratio and half-maximal activation constant (A0.5) for glucose-6-P of glycogen synthase. Because of the dissociation of the effects of insulin on hexose transport and glycogen synthase in muscle of fasted adrenalectomized rats, it is concluded that the impairment in insulin-stimulated hexose transport in these animals is due to a defect lying beyond the interaction of insulin with its receptor.

The alkaloids of Ormosiasemicastrata have been shown to be (−)-ormosanine, (±)-piptanthine, (−)-18-epiormosanine, and (−)-ormocastrine. The structure and relative configuration shown in 1 have been assigned to ormocastrine on the basis of its 220 MHz n.m.r. spectrum and its conversion to ormosanine, among other products, on hydrogenation.

Success with rIL-2 immunotherapy of human cancer appears to depend on the administration of high doses which are frequently associated with excessive toxicity. Future use of rIL-2 will require certain modifications based on the use of lower doses of rIL-2 without significant loss of antitumor efficacy. We tested in vitro the possibility of potentiating the activity of rIL-2 in terms of LAK cell generation. We hypothesized that co-incubation of LAK cell precursors with a Chinese herbal extract (F3) of Astragalus membranaceus, (an immune modulator currently under study in our laboratory), along with a low concentration of rIL-2, would generate levels of LAK cell activity equivalent to those generated by high concentrations of rIL-2 alone. We found (1) a 10-fold potentiation of rIL-2 activity manifested by tumor cell-killing activity of 80% resulting from LAK cell generation with F3 plus 100 u/ml of rIL-2 versus 76% generated by 1,000 u/ml of rIL-2 alone; (2) a significant reduction in the number of effector LAK cells required for equicytotoxic reaction following LAK cell generation with F3 plus rIL-2 compared to rIL-2 alone. We conclude that potentiation of antitumor activity mediated by rIL-2 in low concentrations is possible by the concomitant use of another immune modulator such as Astragalus membranaceus.

The in vitro immunomodulatory activity of fractions derived from Astragalus membranaceus, an herb commonly used in the practice of traditional Chinese medicine, was first screened by studying their individual effects on mononuclear cells (MNC) derived from healthy normal donors using the local xenogeneic graft-versus-host reaction (XGVHR). Sephacryl S-200 column-separated Fraction 3 (MW 20,000-25,000) along with its crude extract precursor, Fraction 7, and another crude extract derivative, Fraction 8, were equally augmentative (p less than 0.05) in their effect on MNC from normal donors. These three active fractions were further studied on MNC derived from 13 cancer patients. Using again the local XGVHR as a model assay for T-cell function, preincubation of MNC derived from cancer patients with Fraction 3 induced a significant increase in local XGVHR (compared to untreated cells) with a mean +/- SD of 151.34 +/- 46.02 mm3 vs 57.80 +/- 16.44 mm3; p less than 0.001. Fractions 7 and 8 likewise induced significant increases in local XGVHR (109.14 +/- 19.32 mm3 versus 50.91 +/- 17.39 mm3; p less than 0.001 and 119.74 +/- 18.33 mm3 versus 48.77 +/- 16.17 mm3; p less than 0.001, respectively). The augmented immune reactions which were induced by either Fraction 3 or Fraction 8 (but not by Fraction 7) in MNC derived from cancer patients, each significantly exceeded the local XGVHR observed in the untreated MNC derived from normal donor controls with a relative reference index (ratio) of 1.60 +/- 0.48 and 1.23 +/- 0.17 respectively; p less than 0.005.(ABSTRACT TRUNCATED AT 250 WORDS)

Through the process of fractionation, purification by gel filtration chromatography and thereafter the screening with an in vitro local xenogeneic graft-versus-host reaction (XGVHR) model, a fraction was identified as a potent immunorestorative agent and was designated "Fraction 3" (F3). Using the XGVHR in vitro as a model assay for T cell function again, F3 was studied on mononuclear cells (MNC) from 13 cancer patients and exhibited significant immunorestorative activity, with an increase in local XGVHR (compared to untreated cells) of 151.34 +/- 46.02 mm3 vs 57.80 +/- 16.44 mm3, P less than 0.001. The in vitro augmented immune reactions induced by F3 in cancer patients also significantly exceeded the local XGVHR observed in the untreated MNC derived from 9 normal donor controls (94.15 +/- 9.16 mm3, P less than 0.005). In a newly developed in vivo XGVHR animal model, pretreatment of rats with F3 resulted in a significant abrogation of the local XGVHR with a reversal of the immunosuppressive effect of cyclophosphamide from 99.42 +/- 9.2 mm3 (positive control) to 39.78 +/- 8.3 mm3 (P less than 0.001). This reversal was complete as the volume of the abrogated local XGVHR was comparable to that of the negative control (no cyclophosphamide-priming, saline injection only) 34.79 +/- 5.69 mm3 (P greater than 0.1). These results suggest that F3 retained the immunopotentiating activity of the original crude extract and form the rational basis for the use of Astragalus in immunotherapy.

Two H4IIE hepatoma cell genes, phosphoenolpyruvate carboxykinase (PEPCK) and gene 33 (g33), are reciprocally regulated by insulin. Quantitation of mRNAPEPCK and mRNAg33 in total RNA isolated from cells treated with insulin showed a 7-fold increase in mRNAg33 amount and a 3-fold decrease of mRNAPEPCK. The cAMP analog 8-(4-chlorophenylthio)-cAMP induced mRNAPEPCK but had no effect on mRNAg33. The responses to various insulins and related molecules showed that the insulin receptor mediates the effects of physiologic concentrations of insulin on each of these genes. This inverse pattern of regulation by insulin was further characterized by determining the transcription rates of both genes in nuclei isolated at various times after the addition of insulin and 8-(4-chlorophenylthio)-cAMP to H4IIE cells. Insulin increased the rate of synthesis of mRNAg33 from 35 to 354 ppm and decreased the synthesis of mRNAPEPCK from 1175 to 109 ppm. These effects of insulin occurred rapidly and reached their maxima by 60 min. In both cases, greater effects were observed as insulin concentrations were increased from 10(-12) to 10(-8) M. Although the effects of insulin were concentration-dependent for both genes, the PEPCK gene was significantly more sensitive to low concentrations of insulin than was gene 33. The reciprocal effects of insulin on the synthesis of mRNAPEPCK and mRNAg33 in H4IIE cells provide a means of investigating how a hormone can exert opposing effects on two genes in the same cell.

SummaryThe capacity for intestinal absorption of glucose in heat and cold-acclimated desert woodrats was studied using an in vitro method. Cold-acclimation had no effect on intestinal serosal transfer, however, heat-acclimation increased the absorptive capacity of the intestine. The alterations in serosal transport of glucose by the intestine may represent a compensatory mechanism for decreased food intake during heat-acclimation.

This paper presents the results of monoclonal immunoglobulin (Ig) determination in 202 patients with malignant lymphoma, 51 with Hodgkin's disease (HD) and 151 with non-Hodgkin's lymphoma (NHL) including 4 patients with mycosis fungoides and 1 with pleomorphic T-cell lymphomas studied from Aug. 1980 to July. 1982. No monoclonal Ig was detected in 4 patients with mycosis fungoides, 51 with HD and 204 normal controls. In the rest 146 patients with NHL, 13 had monoclonal Ig (9%). The types and quantities of monoclonal Ig are discussed. We consider that the presence of monoclonal Ig may be one of the important characteristics of NHL.

A partially purified fraction (F3) with an estimated molecular weight of 20,000 to 25,000 derived from the traditional Chinese medicinal herb Astragalus membranaceus, was found to possess a potent immunorestorative activity in vitro. Its capacity to aborogate the local xenogeneic graft versus host reaction (XGVHR) following injection in vivo was further studied in a newly developed animal model designed for preclinical evaluation of various biological response modifiers. F3 was injected intravenously into cyclophosphamide-primed rats at varied concentrations and schedules prior to grafting of mononuclear cells from healthy normal donors. Maximal abrogation of the local XGVHR mounted by the mononuclear cells, was observed following injection of 5.55 mg of F3 daily for eight days. This abrogation of XGVHR indicates a reversal of the immunosuppressive effect of cyclophosphamide as manifested by a significant decline in the local XGVHR volume from 99.42 +/- 9.2 mm3 (positive control) to 39.78 +/- 8.3 mm3 (p less than 0.001). This reversal of cyclophosphamide-induced immunosuppression by the administration of F3 was complete, since the volume of the abrogated local XGVHR (39.78 +/- 8.3 mm3) was comparable to 34.79 +/- 5.69 mm3 (p greater than 0.1) in the negative control group (no cyclophosphamide-priming; saline injection only). These data indicate that F3 administration markedly enhances the rats' ability to reject the xenogeneic graft and therefore possesses a strong immune potentiating activity in vivo. These preclinical data also provide the rational basis for the use of extracts of Astragalus membranaceus in phase I clinical trials among patients suffering from iatrogenic or inherent immune deficiency states.

Over the past years it was found that modification of the 3-carboxylic acid group of quinolones generally produced compounds with a substantial decrease in antibacterial activity. The 3-carboxylic acid moiety together with the 4-carbonyl function are believed to be the most structurally critical sites for this class of compounds to DNA gyrase. The authors have designed and synthesized a series of quinolone analogues in which the 3-carboxylic acid group has been modified. These compounds, 2,3,4,9-tetrahydroisothiazolo[5,4-b]quinoline-3,4-diones, possess biological activities far superior to their parent counterparts. For example, the MICs (microgram/ml) for A-62824 (ciprofloxacin 3-carboxylic acid modified analogue) and ciprofloxacin against some organisms are as follows: S. aureus ATCC 6538P (0.02, 0.2); S. epidermidis 3519 (0.05, 0.2); E. coli Juhl (0.005, 0.01); P. aeruginosa A5007 (0.05, 0.1) and Acinetobacter sp. CMX 699 (0.05, 0.78). This investigation has produced the first successful modification of the 3-carboxylic acid group of quinolones resulting in a series of extremely potent antibacterials. The design and synthesis as well as the biological activities of these new derivatives are described.