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During a longitudinal study of the epidemiology of rotavirus infection in a calf rearing unit, excretion of virus in faeces was detected by enzyme-linked immunosorbent assay in 40 of 48 (83 per cent) unweaned calves aged between three days and five weeks. Fifty per cent of the infected calves had no clinical signs of disease. Enterocytes containing rotavirus antigen and intestinal lesions were found in all of 12 clinically normal calves selected for necropsy between days 1 and 4 of virus excretion. Stunting and fusion of villi, exfoliation, disarrangement and vacuolation of enterocytes and the presence of cuboidal enterocytes were observed in infected calves but not in rotavirus-free control calves. Lesions predominated in the upper small intestine, where rotavirus was most abundant, especially on the first two days of virus excretion. The numbers of enterocytes infected with rotavirus diminished before the lesions resolved.

Twenty-one moribund calves with diarrhoea were purchased from 11 farms, their faeces examined for enteropathogens and samples of intestinal tissue removed under anaesthesia. Lesions and presence of enteropathogens on the mucosal surface were scored by histological examination of immunostained paraffin sections. Two or more enteropathogens were detected in 19 calves. Cryptosporidium appeared to be the principal cause of diarrhoea in six calves, rotavirus in four, Salmonella typhimurium in two, bacteria adherent to the surface of the large intestine in two, coronavirus in one and K99 + Escherichia coli in one calf. Diarrhoea in four calves was the consequence of mixed infections in which no one enteropathogen appeared to predominate. In one calf no enteropathogen was detected. Diarrhoea was associated with infections and lesions throughout the small and large intestines. The enteropathogens most frequently associated with lesions in the small intestines were rotavirus, coronavirus and Cryptosporidium; in the large intestines they were coronavirus and bacteria apparently adherent to the mucosal surface.

HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) are part of the combination therapy currently used to treat HIV infection. The features of a new NNRTI drug for HIV treatment must include selective potent activity against both wild-type virus as well as against mutant virus that have been selected by use of current antiretroviral treatment regimens. Based on analogy with known HIV-1 NNRTI inhibitors and modeling studies utilizing the X-ray crystal structure of inhibitors bound in the HIV-1 RT, a series of substituted 2-quinolones was synthesized and evaluated as HIV-1 inhibitors.

In oral carcinogenicity bioassays, zidovudine (ZDV) induced vaginal epithelial cell tumors in mice given 30 or 40 mg/kg/day and rats given 300 mg/kg/day. To determine if lifetime exposure to ZDV, beginning perinatally, would alter this pattern of carcinogenicity, two groups of 60 pregnant CD-1 mice were given 20 or 40 mg/kg/day of ZDV in 0.5% methyl cellulose from Gestation Day 10 through Lactation Day 21. At weaning, 2 pups per sex from each of 35 litters in each group were assigned to the study and given 20 or 40 mg/kg/day of ZDV in the drinking water until 17-35 days of age, followed by daily gavage for 24 months. Two additional groups of 60 pregnant CD-1 mice each were given 40 mg/kg/day of ZDV daily from Gestation Day 10 through Lactation Day 21; in one, ZDV treatment was halted at weaning and in the other, treatment was stopped 90 days after weaning. Two other groups of 60 pregnant CD-1 mice were left untreated (environmental control) or were given 0.5% methyl cellulose beginning on Gestation Day 10 (vehicle control). Vehicle control progeny received plain drinking water for 17-35 days postweaning and then 0.5% methyl cellulose daily by gavage for 24 months. ZDV treatment did not affect survival or body weight in either sex. In females given 20 or 40 mg/kg/day of ZDV for 24 months there was mild macrocytic anemia. Similar, non-dose-related changes were seen in males in these groups. ZDV-related tumor findings were limited to the vagina, where there were 2 and 11 vaginal squamous cell carcinomas in mice given 20 or 40 mg/kg/day of ZDV daily, respectively. This incidence was not remarkably different from that seen in previously reported bioassays. It was concluded that lifetime oral treatment of mice with ZDV, beginning perinatally, did not alter the previously reported pattern of carcinogenicity and that under the conditions tested ZDV was not a transplacental carcinogen.

Strategic medication in breeding flocks of domestic fowl (Gallus gallus), using antimicrobial treatment followed by competitive exclusion, was evaluated in 13 trials between February and September 1993. In each trial, the flock had been confirmed as naturally infected with Salmonella enterica serovar Enteritidis and the effect of treatment was determined on salmonella isolation from tissues. Of 11 trials where enrofloxacin was used, a long-term reduction of salmonella was observed in two and a short-term reduction was measured in birds from another five trials. Salmonella Enteritidis was isolated from birds after treatment in four other trials with enrofloxacin and in two trials of medication with amoxycillin. After treatment with enrofloxacin significant reductions were found in the prevalence of 5. Enteritidis in tissues from birds, and in levels and prevalence of salmonellas in their environment. No salmonella was identified in statutory meconium samples taken from the hatched chicks derived from the flocks after treatment. The programme of antibiotic treatment and competitive exclusion offers an alternative to slaughter, but the approach must be part of a co-ordinated programme which will effect a decrease in the prevalence of 5. Enteritidis over time by contemporary use of disease security measures. The risk of development of antimicrobial resistance is also discussed.

Helicobacter pylori has been widely studied since its discovery in 1982 by Marshall and Warren (1), but many aspects of its structure, metabolism, and physiology, including its specific growth requirements, are still largely unknown, The organism is generally grown in complex media containing tissue extracts (e.g., of brain or heart) or proteolytic enzyme digests of meat or casein supplemented with blood or serum, which has made the metabolic pathways utilized by the bacterium difficult to determine. For example, although early studies based on acid formation from sugars and detection of preformed enzymes found no evidence of saccharide fermentative pathways (2,3), more recent evidence indicates that H. pylori does indeed catabolize sugars. In a series of studies, Mendz, Hazell, and colleagues found clear evidence for the pentose phosphate pathway (4), glucokinase activity (5), and the fermentation of glucose to lactate (6).

6-Methoxypurine arabinoside [9-(β-D-arabinofuranosyl)-6-methoxy-9H-purine; 1] is a potent and selective agent against varicella-zoster virus in vitro. Studies in the rat indicated that extensive first pass metabolism of this nucleoside occurred after oral dosing, presumably from high levels of adenosine deaminase in the intestine. Only 3.8% of an oral dose of 6-methoxypurine arabinoside was recovered in the urine. In an attempt to improve these unfavourable pharmacokinetics, a series of twenty-five 2′-esters of 6-methoxypurine arabinoside were prepared either by direct acylation or by a protection, acylation, and deprotection sequence. These esters were evaluated in the rat for their suitability as prodrugs on the basis of urinary recovery of 1 after oral dosing. The straight-chain aliphatic esters, but not the branched chain or aromatic esters, improved this urinary recovery. The 2′-valerate, hexanoate, heptanoate, and octanoate esters (2d–g, respectively) were the most effective, with urinary recoveries of 1 above 15%. The water solubility of the valerate ester was high (107 mM at 37°C and pH 7.2), but solubilities progressively decreased with the longer chain esters. The combination of high water solubility and improved metabolic stability upon oral dosing made 2d the prodrug of choice for both oral and intravenous dosing.

The microfilament-disrupting drug cytochalasin D and, initially, inoculation at 20 degrees C were used to differentiate between phagocytosis (sensitive to both treatments) and pinocytosis (resistant to both treatments) to assess whether chlamydial uptake into McCoy cells occurred by one or both mechanisms and whether each could contribute to productive infection. Both treatments suppressed the infectivity of Chlamydia trachomatis L2/434/Bu and C. psittaci GPIC (the guinea pig inclusion conjunctivitis strain) following static inoculation by only 50%, indicating that there was simultaneous operation of both phagocytosis and pinocytosis during uptake that led to productive infection. Measurement of the entry of organisms by two separate assays established that both strains predominantly used a cytochalasin D-resistant (pinocytic) mechanism, implying that phagocytic uptake was coupled to a higher frequency of productive infection. Integration of the data on infectivity and entry allowed the potential for an organism to infect a host cell to be quantified. This synthesis revealed that for both strains the infectivity potential following phagocytic entry was ca. 10-fold greater than that following pinocytic entry. However, both entry mechanisms were exploited more efficiently by strain L2/434/Bu than by strain GPIC (unless the latter was inoculated with centrifugation), indicating that intrinsic strain properties are more important for infectivity potential than the endocytic mechanism utilized.

This article is a summary of some of the more recent research on the diagnosis, etiology, and treatment of Cluster B personality disorders (antisocial, histrionic, borderline, and narcissistic). Research on psychological, psychosocial, and biological perspectives of these disorders is presented. Individual psychotherapy, group psychotherapy, and other forms of multi-person therapies are also discussed. Finally, perspectives on issues of countertransference when treating these personality-disordered patients are addressed.

The decision as to whether prophylaxis against postoperative nausea and vomiting is better than treatment of established postoperative nausea and vomiting could be made on the basis of cost-effectiveness. The cost-effectiveness of ondansetron was calculated using data from published quantitative systematic reviews of randomised trials. Milligrams of ondansetron required to achieve a desired endpoint were chosen as a cost unit. Modelling was based on a cohort of 1000 patients, and examined control event rates (i.e. incidence of postoperative nausea and vomiting without prophylaxis) of between 10 and 90%. In a sensitivity analysis, cost-effectiveness of recommended intravenous doses (4 mg for treatment and prophylaxis) was compared with minimal effective doses as shown by meta-analysis (1 mg for treatment, 8 mg for prophylaxis). Fewer patients experience any postoperative nausea and vomiting symptoms with prophylaxis compared with treatment. But prophylaxis is only marginally more effective than treatment, and treatment of established postoperative nausea and vomiting with effective doses (i.e. 1 or 4 mg) is more cost-effective and safer than prophylaxis with effective doses (i.e. 4 or 8 mg). Reasons for this are the selective treatment of patients who actually need treatment, the high success rate with a lowest dose tested (1 mg) in established postoperative nausea and vomiting, and the disappointing antinausea effect of prophylactic ondansetron even at an eight-fold higher dose.

The authors reviewed efficacy and safety data for ondansetron for preventing postoperative nausea and vomiting (PONV).Systematically searched, randomized, controlled trials (obtained through MEDLINE, EMBASE, Biological Abstracts, manufacturer's database, manual searching of journals, and article reference lists) were analyzed. Relevant end points were prevention of early PONV (within 6 h after surgery) and late PONV (within 48 h) and adverse effects. Relative benefit and number-needed-to-treat were calculated. The number-needed-to-treat indicated how many patients had to be exposed to ondansetron to prevent PONV in one of them who would have vomited or been nauseated had he or she received placebo.Fifty-three trials were found that had data from 7,177 patients receiving 24 different ondansetron regimens and from 5,712 controls receiving placebo or no treatment. Average early and late PONV incidences without ondansetron were 40% and 60%, respectively. There was a dose response for oral and intravenous ondansetron. Best number-needed-to-treat to prevent PONV with the best documented regimens was between 5 and 6. This was achieved with an intravenous dose of 8 mg and an oral dose of 16 mg. Antivomiting efficacy was consistently better than antinausea efficacy. Efficacy in children was poorly documented. Ondansetron significantly increased the risk for elevated liver enzymes (number-needed-to-harm was 31) and headache (number-needed-to-harm was 36).If the risk of PONV is very high, for every 100 patients receiving an adequate dose of ondansetron 20 patients will not vomit who would have vomited had they received placebo. The antinausea effect is less pronounced. Of these 100, three will have elevated liver enzymes and three will have a headache who would not have had these adverse effects without the drug.

Helicobacter pylori possesses up to six, unipolar sheathed flagella which appear essential for the colonization of the gastric mucosa.1 The flagellins, FlaA and FlaB, have been characterized and the genes which encode them thoroughly analyzed.5,8 However, relatively little is known about the flagellar sheath, which is an unusual structure common to all members of the genus.

An engine rig test and a scuffing BOCLE test have been used to investigate the lubricity of low sulfur diesel fuels and its relationship with unit injector wear in heavy duty diesel engines. The rig test effectively ranks 11 selected fuels/fluids according to their actual performance. The scuffing BOCLE test correlates with the rig test by showing the same ranking capability, and it is easy to perform. A similar correlation has been established using ISO reference fuels. The scuffing BOCLE test has been to study 37 fuels randomly sampled from the field. The data shows that there is indeed a reduction in lubricity of low sulfur fuels. The variation in lubricity of low sulfur fuels is also much greater than high sulfur fuels. Data in this study shows that transition from good to poor lubricity usually occurs between 2500 to 3000 grams in the scuffing BOCLE. 7 refs., 4 figs., 6 tabs.

The binding of [3H]inositol hexakisphosphate ([3H] InsP6) to rat cerebellar membranes has been characterized with the objective of establishing the role, if any, of a membrane protein receptor. In the presence of EDTA, we have previously identified an InsP6-binding site with a capacity of approximately 20 pmol/mg protein (Hawkins, P. T., Reynolds, D. J. M., Poyner, D. R., and Hanley, M. R. (1990) Biochem. Biophys. Res. Commun. 167, 819-827). However, in the presence of 1 mM Mg2+, the capacity of [3H]InsP6 binding to membranes was increased approximately 9-fold. This enhancing effect of Mg2+ was reversed by addition of 10 microM of several cation chelators, suggesting that the increased binding required trace quantities of other metal cations. This is supported by experiments where it was possible to saturate binding by addition of excess membranes, despite not significantly depleting radioligand, pointing to removal of some other factor. Removal of endogenous cations from the binding assay by pretreatment with chelex resin also prevents the Mg(2+)-induced potentiation. Consideration of the specificity of the chelators able to abolish this potentiation suggested involvement of Fe3+ or Al3+. Both these ions (but not several others) were able to increase [3H]InsP6 binding to chelex-pretreated membranes at concentrations of 1 microM. It is possible to demonstrate synergy between Fe3+ and Mg2+ under these conditions. We propose that [3H]InsP6 may interact with membranes through non-protein recognition, possibly via phospholipids, in a manner dependent upon trace metals. The implications of this for InsP6 biology are considered.

Grease-gap recordings revealed that 5-hydroxytryptamine (5-HT) depolarized the ferret vagus nerve (pEC50 = 4.9). This response was mimicked by 2-methyl-5-HT and 1-phenylbiguanide, but not by 5-carboxamidotryptamine. Paroxetine (1 microM) or ketamine (10 microM) did not potentiate the response. Ketanserin (1 microM) did not reduce the depolarization, but four 5-HT3 receptor antagonists did. It is concluded that 5-HT depolarizes the ferret vagus nerve via 5-HT3 receptors, but these receptors may differ pharmacologically from those in other species.

N(4-Methylphenyl)diphenimide proved to be an effective hypolipidemic agent in rats at 10 and 20 mg/kg/day. Both serum cholesterol and triglyceride levels were reduced significantly. Decreases in tissue lipids as well as VLDL cholesterol levels were observed. HDL-cholesterol was elevated even at 10 mg/kg/day. The agent was equally effective in hyperlipidemic diet-induced rats, lowering serum lipids and VLDL- and LDL-cholesterol while elevating HDL-cholesterol levels. The drug interfered with the incorporation of 3H-cholesterol and 3H-palmitic acid into chylomicrons, VLDL, and LDL. The two precursors were incorporated at a higher rate into HDL. 3H-Leucine was incorporated into chylomicrons, VLDL, and LDL at a higher rate, but not into HDL. Reduced uptake of the precursor for lipid synthesis was noted in tissues after treatment with the drug.

4-Phenyl-5,5-dicarbethoxy-2-pyrrolidenone [XIV] treatment in Sprague Dawley rats caused significant reduction of serum cholesterol and triglyceride levels with reduction of VLDL and LDL cholesterol levels. The compound significantly reduced regulatory enzyme activities, e.g. ATP dependent citrate lyase, HMG CoA reductase, acyl CoA cholesterol acyl transferase, cholesterol-7-alpha-hydroxylase, sn-glycerol-3-phosphate acyl transferase and phosphatidylate phosphohydrolase. In tissue cultured cells, the compound suppressed LDL receptor activity and degradation, and elevated HDL receptor activity and HDL degradation. Rat bile cholesterol and phospholipids were elevated; however, overall bile acids were reduced. In situ loop studies suggest that the agent interfered with interhepatic reabsorption of cholesterol and cholic acids. At the therapeutic dose of compound XIV, no deleterious effects were demonstrated in mice.

The cytochalasin D-resistant (pinocytic) portion of the entry of two chlamydia strains (Chlamydia trachomatis L2/434/Bu and Chlamydia psittaci GPIC [guinea pig inclusion conjunctivitis]) was examined. By ultrastructural criteria, few organisms of either strain were observed in association with coated host-cell plasma membrane during entry into McCoy cells; this argues against a coated-pit mechanism of entry. When association with a coated membrane was seen, coat material appeared to pinch off ahead of internalizing chlamydiae. However, entry of both strains was substantially reduced by cytosol acidification, a procedure shown to prevent coated-pit vesiculation (K. Sandvig, S. Olsnes, O. W. Petersen, and B. van Deurs, J. Cell Biol. 105:679-689, 1987). No conclusive evidence of displacement of the fluid-phase marker [3H]sucrose from constitutively forming endocytic vesicles was found. Indeed the entry of strain 434 (but not strain GPIC) was accompanied by the influx of a large volume of fluid, suggesting an inducible mechanism. Additionally, entry of strain 434 (but not strain GPIC) was partially inhibitable by amiloride, yet the drug had no effect on the entry of transferrin, a ligand known to enter solely via coated pits. Our findings endorse the view that chlamydial entry can occur via a pathway involving coated pits. However, the unusual morphology of entry and lack of fluid exclusion are consistent with a process whereby although chlamydiae are not fully enclosed by coat material, their entry is dependent on the vesiculation of coated pits. Furthermore, the data support the proposition that a significant proportion of the entry of strain 434 occurs via an inducible pathway independent of coated-pit uptake.

An X-ray scattering study is presented of the lamellar/nematic/isotropic sequence in the lyotropic system DACI/H2O/NH4Cl. The whole reciprocal space of monocrystalline samples oriented in magnetic fields are reconstructed from their two dimensional sections on photographic films. Intense diffuse scatterings are observed in the lamellar phase, around and away from the Bragg spots. Their evolution close to the lamellar/nematic transition reveals the presence of intense structural fluctuations. They take place over temperature ranges which are significantly greater than those associated with the smectic/nematic transitions in thermotropic liquid crystals. A similar situation is observed in the isotropic phase in the vicinity of the nematic/isotropic transition.

Molecular orbital calculations using CNDO/S parameters are employed to determine bond-orders, charge-densities and the shielding of the 15 N and 13 C nuclei of a series of ureas and thioureas. For the sterically uncrowded molecules a linear relationship is noticed between the 15 N chemical shifts and CN bond-orders. When steric crowding occurs this simple relationship is no longer applicable.

An indirect immunoperoxidase technique has been used to identify enteropathogens in formol-sublimate fixed paraffin embedded sections of calf intestine. Infections with bovine rotavirus, bovine coronavirus, Newbury agent SRV -1, and K99+ Escherichia coli have been detected in the intestines from experimentally infected and conventially reared diarrhoeic or normal calves. The ability to visualize enteropathogenic agents in histological sections resulted in the demonstration of virus infected cells at sites not previously shown to be infected using the immunofluorescence technique.

Summary An immunofluorescence test on smears of nasal epithelial cells was used to detect coronavirus infection in the respiratory tract of calves. Thirteen gnotobiotic calves were infected with coronavirus isolates derived from faeces or respiratory material: virus was detected in faeces and nasal swabs from all animals. In 115 calves from a field survey, there was a significant association between coronavirus excretion from both respiratory and enteric routes in calves with diarrhoea. In a further 12 calves, at necropsy, the predilection sites for coronavirus growth were the distal small intestine, large intestine and the epithelia of the nasal cavity and trachea. Antigen was not found in lung tissue by immunofluoresence or immunoperoxidase staining. Infection with enteric coronavirus induced immunity to reinfection and to heterologous challenge with two coronavirus isolates derived from the respiratory tract. Nine coronaviruses were cultivated, cloned and antisera to three were prepared in pigs. There was complete virus neutralisation in tests with homologous sera and significant cross reactions with the eight other isolates which were of intestinal and respiratory origin. Thus, these bovine coronavirus isolates belonged to the same serotype despite the source of virus.

For a series of compounds with NC or NN bonds, the CNDO/S parameterized calculations for Qπ, the electronic charge density on the nitrogen atom, and π bond orders Pπ provide evidence for the simultaneous dependence of the 15N chemical shift on both of these parameters. The multilinear regressions obtained produce high values for the regression coefficients. The results throw some light on the nitrogen lone pair delocalization mechanism.

Summary Transmissible gastroenteritis virus was administered orally to cats. No clinical disease resulted but infectious virus was isolated from faeces for up to 22 days after infection and serum antibody was detected by neutralisation and immunofluorescence tests.

Summary A possible antigenic relationship between the porcine enteropathogenic coronavirus-like agent (CVLA) and 6 known coronaviruses was examined by immunoelectron microscopy (IEM) and by immunofluorescence (IF). CVLA did not show cross reactivity with infectious bronchitis virus, transmissible gastroenteritis virus (TGEV), canine coronavirus (CCV) hemagglutinating encephalomyelitis virus (HEV), neonatal calf diarrhea coronavirus (NCDCV) or feline infectious peritonitis virus (FIPV). Antigenic relationship was detected by IEM between TGEV and CCV, NCDCV and HEV and by IF between TGEV and CCV, TGEV and FIPV, HEV and NCDCV.

The mesogenic unit of lyotropic nematic liquid crystals is either a columnar (NC) or discoid (ND) micelle. There is growing evidence that these micelles exist as discrete entities in both the isotropic phase and for disk shaped micelles, in the lamellar phase bounding the nematic. Here, the evolution of micelle size as measured by X-ray scattering from orientated samples of caesium perfluorooctanoate/water, has been followed as a function of concentration and temperature across all three phases. The micelle size is found to initially increase with increasing amphiphile concentration, but to decrease at higher concentrations. This behaviour is shown to be consistent with an attractive interaggregate interaction.

We report preliminary results of a three dimensional Monte-Carlo study of a system of anisometrically interacting particles possessing both translational and orientational freedom. A simple interaction potential has been used to generate equilibrium values for the translational order parameter in addition to the long and short range orientational order parameters.

The observed vibrational spectra of bismuth pentafluoride, tin tetrafluoride, and selenium dioxide are assigned on the basis of single-crystal Raman studies and normal-co-ordinate analyses. In the case of the fluorides the nature of the vibrational modes is discussed in some detail. The Raman spectrum of gaseous selenium dioxide shows one strong band at 923 cm–1.

Some shielding calculations, using Pople's SOS model, are reported for B, C, N, F, P and Si as a function of changes in bond length and pyramidal bond angle. In all cases considered, the shielding is predicted to decrease as the bond length increases, which is in line with the available experimental data. The observed temperature variation of the nitrogen and phosphorus shieldings of NH3, PH3 and PF3 could be accounted for by a decrease in the pyramidal angle at higher temperatures. A similar angular variation for NF3 is predicted to cause a shielding variation, with temperature, in the same sense as that reported for NH3 and PH3, but opposite to that for PF3.

The frequencies of the title compounds are computed using a simple force‐field transference scheme. On the basis of these calculations, and gas‐phase Raman spectroscopy of PF5, ν7 for this molecule is assigned at 175 cm−1. An assignment of the species PF3Cl2 is suggested.

Canine coronavirus (CCV) isolate 1-71 was grown in secondary dog kidney cells and purified by rate zonal centrifugation. Polyacrylamide gel electrophoresis revealed four major structural polypeptides with apparent mol. wt. of 203800 (gp204), 49800 (p50), 31800 (gp32) and 21600 (gp22). Incorporation of 3H-glucosamine into gp204, gp32 and gp22 indicated that these were glycopolypeptides. Comparison of the structural polypeptides of CCV and porcine transmissible gastroenteritis virus (TGEV) by co-electrophoresis demonstrated that TGEV polypeptides corresponded closely, but not identically, with gp204, p50 and gp32 of CCV and confirmed that gp22 was a major structural component only in the canine virus. The close similarities in structure of the two coronaviruses augments the relationship established by serology.

2,3-Dihydrophthalazine-1,4-dione effectively lowers serum levels of cholesterol and triglycerides in Sprague Dawley rats after two weeks, after which the cholesterol levels continued to decline. The maximum serum lipid lowering effect on cholesterol or triglyceride levels was during the seventh and eighth week of drug administration. Similar magnitudes of reduction in lipids were observed in hyperlipidemic diet induced mice after four weeks of drug administration of 20 mg/kg.day. Lipid levels in liver, small intestines and aorta wall tissue were significantly reduced after eight weeks of drug administration, but no significant increase in fecal lipids was noted. The cholesterol content in the chylomicrons and in the VLDL and LDL-fractions was significantly reduced whereas HDL cholesterol was elevated by 112%. Neutral lipids and the triglyceride content were not altered in the chylomicron, VLDL and LDL; however, reductions of both levels were observed in the HDL fraction. The phospholipid content was reduced in the LDL and elevated in the other three fractions. Incorporation studies into lipoprotein fractions showed a decrease in cholesterol incorporation in chylomicrons, VLDL and LDL with an increase in HDL cholesterol incorporation. Palmitic acid incorporation was reduced in the chylomicron, VLDL and HDL fractions. 32P-Incorporation was reduced in the HDL fraction. Leucine incorporation into the apoproteins of all four fractions was elevated. Rate limiting enzymes involved in de novo cholesterol, fatty acid and triglyceride synthesis were inhibited by 2,3-dihydrophthalazine-1,4-dione after eight weeks of administration. There was no evidence that the drug caused an increase in peroxisome formation as measured by liver catalase activity nor the release of lysosomal hydrolytic enzymes as measured by acid phosphatase and cathepsin activities. The drug afforded no deleterious effects on clinical chemistry parameters after eight weeks administration.

A dysentery syndrome was recognized among the Institute's calves at 18 to 21 days of age. It was reproduced experimentally in gnotobiotic calves with an atypical Escherichia coli (S102-9) isolated from the affected calves. In both natural and experimental disease the calves passed copious bright red blood in the feces and developed diarrhea. Walls of the colon and rectum were thickened, and the mucosa was reddened and covered by an exudate that contained mucus and blood clots. Bacteria were seen closely adherent to the luminal surfaces of enterocytes, often in cup-shaped depressions or on cytoplasmic pedestals. Microvilli were distorted, disorientated or absent. There was exfoliation of infected enterocytes and a mild acute inflammation of the underlying lamina. In two of five calves with natural disease, the adherent bacteria did not stain by the immunoperoxidase method with antisera raised against E. coli (S102-9). This indicated that there was possibly more than one bacterial cause of the syndrome. Lesions in experimentally infected calves were indistinguishable from those produced by some E. coli which are enteropathogenic for man, rabbits, and pigs.