Measurement of the Nucleon F_{2}

The ratio of the nucleon F_{2} structure functions, F_{2}^{n}/F_{2}^{p}, is determined by the MARATHON experiment from measurements of deep inelastic scattering of electrons from ^{3}H and ^{3}He nuclei. The experiment was performed in the Hall A Facility of Jefferson Lab using two high-resolution spectrometers for electron detection, and a cryogenic target system which included a low-activity tritium cell. The data analysis used a novel technique exploiting the mirror symmetry of the two nuclei, which essentially eliminates many theoretical uncertainties in the extraction of the ratio. The results, which cover the Bjorken scaling variable range 0.19

Precision measurement of the weak mixing angle in Møller scattering.

We report on a precision measurement of the parity-violating asymmetry in fixed target electron-electron (Møller) scattering: A(PV) = [-131 +/- 14(stat) +/- 10(syst)] x 10(-9), leading to the determination of the weak mixing angle sin2(thetaW(eff) = 0.2397 +/- 0.0010(stat) +/- 0.0008(syst), evaluated at Q2 = 0.026 GeV2. Combining this result with the measurements of sin2(thetaW(eff) at the Z0 pole, the running of the weak mixing angle is observed with over 6sigma significance. The measurement sets constraints on new physics effects at the TeV scale.

Experimental determination of the evolution of the Bjorken integral at low Q2.

We extract the Bjorken integral Gamma1(p-n) in the range 0.17 < Q2 < 1.10 GeV2 from inclusive scattering of polarized electrons by polarized protons, deuterons, and 3He, for the region in which the integral is dominated by nucleon resonances. These data bridge the domains of the hadronic and partonic descriptions of the nucleon. In combination with earlier measurements at higher Q2, we extract the nonsinglet twist-4 matrix element f2.

Observation of parity nonconservation in møller scattering.

We report a measurement of the parity-violating asymmetry in fixed target electron-electron (Møller) scattering: A(PV)=[-175+/-30(stat)+/-20(syst)] x 10(-9). This first direct observation of parity nonconservation in Møller scattering leads to a measurement of the electron's weak charge at low energy Q(e)(W)=-0.053+/-0.011. This is consistent with the standard model expectation at the current level of precision: sin((2)theta(W)(M(Z))((-)MS)=0.2293+/-0.0024(stat)+/-0.0016(syst)+/-0.0006(theory).

Q2 evolution of the generalized Gerasimov-Drell-Hearn integral for the neutron using a 3He target.

We present data on the inclusive scattering of polarized electrons from a polarized 3He target at energies from 0.862 to 5.06 GeV, obtained at a scattering angle of 15.5 degrees. Our data include measurements from the quasielastic peak, through the nucleon resonance region, and beyond, and were used to determine the virtual photon cross-section difference sigma(1/2)-sigma(3/2). We extract the extended Gerasimov-Drell-Hearn integral for the neutron in the range of four-momentum transfer squared Q2 of 0.1-0.9 GeV2.

A Staphylococcus aureus paraspinal abscess associated with epidural analgesia in labour.

A case is described in which a parturient developed a Staphylococcus aureus paraspinal abscess following epidural analgesia in labour. We compared this case with other reported cases of paraspinal abscesses in obstetric patients. The presentation, diagnosis and management of these cases were reviewed. Anaesthetists need to be aware that non-spinal-epidural abscesses can occur in patients with an associated labour epidural.

Inhalation teratology and reproduction studies with 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123).

HCFC 123 is one of the chemicals being developed as a replacement for CFC 11 in refrigerant and solvent applications. Supplementing earlier rat teratology studies, a rabbit inhalation teratology study was conducted. In addition, one-generation and two-generation inhalation reproduction studies were conducted. In the teratology study, the pregnant rabbits were exposed to levels of 0 (control), 500, 1500, and 5000 ppm, 6 hr per day from Days 6 through 18 of gestation. Slight body weight losses and reduced food consumption were seen in does in all three exposure level groups. This response followed an exposure-related pattern. There were no other signs of maternal toxicity. There was also no evidence of treatment-related effects on the kits. A probe one-generation reproduction study was conducted. In this study four groups of 12 male and 12 female rats were exposed to vapors of HCFC 123 6 hr per day, 7 days per week from 4 weeks prior to mating through weaning of their offspring. The exposure levels for this study were 0 (control), 300, 1000, and 5000 ppm. There were no effects on mating and fertility, or on pup survival or birth weight. A two-generation study was subsequently conducted. In this study, five groups of 32 male and female rats were exposed to HCFC 123 from 6 weeks of age through weaning. From the offspring of these animals, groups of 28 males and females were selected for the F1 generation. These animals were exposed to HCFC 123 from weaning (4 weeks of age) through weaning of the F1 generation. All exposures were 6 hr per day, 7 days per week. The exposure levels for this study were 0 (control), 30, 100, 300, and 1000 ppm. There were no effects on any of the fertility or reproductive indices measured. As with prior studies, decreases in serum triglyceride levels were seen. Pup survival and birth weight were unaffected by treatment. Pup body weight gain was lower in all treatment groups during nursing, following an exposure-related pattern. Since weight gain for the F1 animals was normal following weaning, this depression of body weight gain may be related to the depression of serum triglycerides. In addition, liver weights of the adult rats exposed to levels of 100 ppm and higher of HCFC 123 were higher than controls, histological examination revealed only hepatic enlargement and vacuolation. It was concluded that exposure to HCFC 123 did not cause reproductive effects although it did effect the body weight gain of the offspring during lactation.

HFA-134a (1,1,1,2-tetrafluoroethane): effects of inhalation exposure upon reproductive performance, development and maturation of rats.

1. HFA-134a was administered to AHA rats by snout-only inhalation for 1 h daily to assess the effects of treatment on reproduction and development. 2. In a fertility study, rats were exposed to atmospheres of 2500, 10,000 or 50,000 p.p.m. HFA-134a throughout gametogenesis, mating, pregnancy and lactation. 3. In a peri- and post-natal study, rats were exposed to HFA-134a from days 17 to 20 of pregnancy and days 1 to 21 post partum to atmospheres of 1800, 9900 or 64,400 p.p.m. 4. The only treatment-related effect was a slight reduction in body weight gain of males of the treated parental generation at 50,000 p.p.m. (fertility study). 5. In neither study were there any adverse effects of HFA-134a on the reproductive performance of treated animals or on the development, maturation or reproductive performance of up to two successive generations.

Reproductive toxicity studies of ademetionine.

S-Adenosyl-L-methionine sulphate-p-toluene sulphonate (ademetionine, SAMe), a donor of methyl groups, was examined for effects upon embryofoetal toxicity following both premating treatment and treatment during pregnancy and for peri- and post-natal toxicity in the rat at dosages of 0, 100, 200 and 400 mg/kg/d SAMe ion by subcutaneous or intravenous administration. Embryofoetal toxicity was also examined in the New Zealand White rabbit at dosages of 0, 10, 20 and 40 mg/kg/d SAMe by intravenous administration. Treatment was considered to be without adverse effect upon any of the reproductive parameters examined on either F0 or on the untreated F1 generations. There was no indication that treatment adversely affected the litter parameters including the incidences of malformations, anomalies and skeletal variants. Some slight changes in the activity of the F1 females derived from F0 animals given 400 mg/kg/d were considered to be of minimal importance. In contrast to the above, adverse effects upon the parents were noted at 400 mg/kg/d including local tissue reaction at the injection sites and retardation of body weight gain. In the intravenous studies some rigidity and dyspnoea were noted following administration. Following subcutaneous premating treatment there was also evidence of histopathological change to the kidney of the female rat. Increased water consumption was noted in this latter study and amongst females rearing offspring in the embryo foetal toxicity study in which the compound was administered intravenously. At the lower dosages administered to the rat some local tissue reaction was evident as was some retardation of body weight gain, minimal at the lowest intravenous dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Surface coil localization of 31P NMR signals from orthotopic human kidney and liver.

By incorporating the hyperbolic secant inversion pulses with the image-selected in vivo spectroscopy localization technique and by applying a gradient-echo imaging method, we have selected only the 31P NMR signals from orthotopic human kidney and liver, using a single concentric 1H/31P surface coil. Corresponding to the experimental results on animal studies, the phosphocreatine signal is dramatically reduced in the localized spectra. Our localization strategy also allows us to shim easily on the well-defined volume of interest and leads to high-resolution spectra that exhibit multiplet structure. Our results indicate that we can obtain localized signals from deep small organs and point the way for other human metabolism studies.

Reproductive toxicity studies of rentiapril.

(2R,4R)-2-(o-Hydroxyphenyl)-3-(3-mercaptopropionyl)-4- thiazolidinecarboxylic acid (rentiapril, SA 446), an orally active inhibitor of angiotensin converting enzyme, was examined for effects upon general reproductive performance, for embryofoetal toxicity and for peri- and postnatal toxicity in the rat at dosages of 0, 20, 100 and 500 mg/kg/d. Embryofoetal toxicity was also examined in the New Zealand White rabbit at dosages of 0, 1, 2 and 4 mg/kg/d. The compound was administered by gastric intubation. Prolonged treatment at 100 and 500 mg/kg/d during the fertility study was associated with some slight depression of body weight gain of males. Body weight gain of females during gestation was significantly depressed at 500 mg/kg/d. There was salivation in both sexes at 500 mg/kg/d and also in males receiving 100 mg/kg/d. Following this prolonged treatment in the fertility study. Fo male and female kidney weights were increased at all dosages. Although there was no obvious effect upon fertility there was an increased incidence of total litter loss at 500 mg/kg/d and mean pup weights to day 21 post partum were reduced at this dosage and at 100 mg/kg/d with delays in the attainment of some of the developmental landmarks. In the rat treatment at 500 mg/kg/d from day 7 to 17 of pregnancy did not adversely effect embryofoetal development. Subsequent development and reproductive performance of the F1 offspring was also unimpaired. During this treatment period signs of salivation were seen at 500 mg/kg/d. Slight retardation of maternal body weight gain was noted at 500 mg/kg/d and at 100 mg/kg/d but not at 20 mg/kg/d.(ABSTRACT TRUNCATED AT 250 WORDS)

On the assessment of the beta-adrenoceptor blocking activity of propranolol using the rat isolated right ventricle.

Two methods for determining pA2 values, the Schild regression and the use of the formula pA2 = pAx + log(x - 1), have been reassessed. The effects of propranolol on the contractile responses of the rat isolated right ventricle to isoprenaline were studied. The inhibitory effect with the lower concentrations of propranolol tested (3 X 10(-9) -10(-7) M) was solely competitive. Thus there was a parallel dextral displacement of the concentration-response curves to isoprenaline with no depression of the maximal responses. Dual antagonism was observed with the higher concentrations of propranolol tested (10(-6) and 3 X 10(-6) M), thereby showing a parallel displacement of the concentration-response curve to the lower concentrations of isoprenaline with a depression of the maximal responses. Without analysis of data for individual concentrations of propranolol on concentration-response curves to isoprenaline, Schild regression did not clearly illustrate that the antagonism was not solely competitive with the higher concentrations of propranolol. We suggest that data for individual concentrations of antagonist should always be analyzed to ascertain whether there has been a parallel shift of the concentration-response curves to agonist prior to determining pA2 values.

The effects of KF-4317, a novel combined alpha- and beta 1-adrenoreceptor antagonist, on the rat isolated right ventricle and aorta.

The effects of KF-4317 on the accumulation of radioactivity from [3H]-noradrenaline, and on the subsequent spontaneous and noradrenergic nerve-evoked outflow of radioactivity have been investigated in the rat isolated right ventricle. In addition the effects of KF-4317 on the contractions of the electrically-driven directly muscle stimulated rat right ventricle to isoprenaline and of the rat isolated aorta to phenylephrine and 5-hydroxytryptamine are reported. KF-4317 at 1 microM had no effect on the ability of the rat right ventricle to accumulate radioactivity from [3H]-noradrenaline. The spontaneous outflow of radioactivity, following loading of the ventricle with [3H]-noradrenaline, was increased by KF-4317 at 1 microM by a cocaine-insensitive mechanism. KF-4317 at 1 microM had no effect on the noradrenergic nerve-evoked outflow or radioactivity, and therefore is not an alpha 2-adrenoreceptor antagonist, but reduced the associated contractile response probably mainly by acting as an antagonist at postjunctional beta 1-adrenoreceptors. KF-4317 caused a parallel rightward shift of the concentration-response curve of the electrically-driven directly muscle stimulated rat right ventricle to isoprenaline. However the inhibitory effect, X9.0 and X237.2 in the presence of 0.1 and 1 microM KF-4317, was not closely concentration-related. At 1 microM, KF-4317 also depressed the maximum responses to isoprenaline. This suggests that in addition to beta 1-adrenoreceptor antagonism, KF-4317 probably exerts membrane stabilizing activity. The responses of the rat isolated aorta to phenylephrine were inhibited in a non-concentration related manner by KF-4317.(ABSTRACT TRUNCATED AT 250 WORDS)

Proteoglycan-collagen relationships in developing chick and bovine tendons. Influence of the physiological environment.

Developing and mature flexor digitorum tendons of chick and bovine origin were analyzed for nucleic acid, hydroxyproline, hyaluronate, chondroitin sulfate and sulfated glycosaminoglycan hexuronate. Collagen fibril diameters were determined by electron microscopy. Results are compared with similar data from rat tail tendon. Tissue hydroxyproline (mg/g) increased rapidly in early embryogenesis, while collagen fibril diameters remained relatively constant and small. Hyaluronate and chondroitin sulfate were present in considerable quantities, (phase I). A rapid increase in fibril diameters in midterm 'pregnancy' coincided with a decrease in hyaluronate and chondroitin sulfate contents (phase II). The transition from phase I to phase II was associated with the first loading by active muscles of the tendon, independently of whether the animal was pre- or post partum. The probable existence of a developmental program intrinsic to tendon itself, is discussed. The data are compared with predictions from three different simple models. Hyaluronate is concluded to be entirely interfibrillar, chondroitin sulfate is probably similarly distributed, whereas dermatan sulfate is entirely fibril-surface associated. The 'small' dermatan sulfate proteoglycan is assigned to the 'd' band in the gap zone.

Comparison of the effects of labetalol and SCH 19927, the R1R isomer of labetalol, on the rat isolated right ventricle and aorta.

The effects of labetalol and its R1R isomer, SCH 19927, on the accumulation of radioactivity from [3H]-noradrenaline, and on the subsequent spontaneous and nerve-evoked outflow of radioactivity have been investigated in the rat isolated right ventricle. In addition, the effect of these agents on the contractions of the electrically-driven rat right ventricle to isoprenaline and of the rat isolated aorta to phenylephrine and 5-hydroxytryptamine are reported. Labetalol and SCH 19927 (both at 10(-6)M) inhibited the accumulation of radioactivity from [3H]-noradrenaline by 26 and 37%, respectively. The spontaneous outflow of radioactivity, following loading of the ventricle with [3H]-noradrenaline, was increased by labetalol and SCH 19927 (both at 10(-6)M) by a cocaine and idazoxan-insensitive mechanism. The nerve-evoked outflow of radioactivity was increased by labetalol and SCH 19927 (both at 10(-6)M). The ability of labetalol and SCH 19927, to increase nerve-evoked outflow was maintained in the presence of cocaine (10(-5)M) or idazoxan (10(-7)M) but reversed in the presence of cocaine and idazoxan. It is suggested that labetalol and its R1R isomer act both to inhibit neuronal uptake of noradrenaline and as antagonists at prejunctional alpha 2-adrenoreceptors. Labetalol and SCH 19927 reduced the contractile responses associated with the nerve-evoked outflow of radioactivity probably mainly by acting as antagonists at postjunctional beta 1-adrenoreceptors. The contractile responses of the electrically-driven rat right ventricle to isoprenaline were inhibited by labetalol and SCH 19927. SCH 12297 (pA2 = 8.9) was 4 times more potent than labetalol (pA2 = 8.3) as a beta 1-adrenoreceptor antagonist. The ability of labetalol and SCH 19927 at greater than or equal to 10(-7)M to depress maximal responses to isoprenaline may represent membrane stabilizing activity. The contractile responses of rat aorta to phenylephrine were inhibited by labetalol and SCH 19927. Labetalol (pA2 = 7.5) was 4X more potent than SCH 19927 (pA2 = 6.9) as an alpha 1-adrenoreceptor antagonist. SCH 19927 and labetalol had no effect on contractile responses to 5-hydroxytryptamine.

The effects of amosulalol, a novel combined alpha- and beta-adrenoreceptor antagonist, on the rat isolated right ventricle and aorta.

The effect of amosulalol on the accumulation of radioactivity from [3H]-noradrenaline and on the subsequent spontaneous and nerve stimulation-evoked outflow of radioactivity have been investigated in the rat isolated right ventricle. In addition the effect of amosulalol on the contractions of the electrically-driven directly muscle stimulated rat right ventricle to isoprenaline and of the rat isolated aorta to phenylephrine and 5-hydroxytryptamine are reported. Amosulalol at 10(-6)M did not prevent the accumulation of radioactivity from a solution containing [3H]-noradrenaline. The spontaneous outflow of radioactivity, following loading of the ventricle with [3H]-noradrenaline, was increased by amosulalol at 10(-6)M by a cocaine- and idazoxan- insensitive mechanism. The nerve stimulation-evoked outflow of radioactivity was increased by amosulalol (10(-6)M), cocaine (10(-5)M) and idazoxan (10(-7)M). The ability of amosulalol to increase nerve-evoked outflow was maintained in the presence of cocaine but prevented by pretreatment with idazoxan. This suggests that amusulalol is an alpha 2-adrenoreceptor antagonist. The contractile response of the electrically-driven directly muscle stimulated right ventricle to isoprenaline were inhibited by amosulalol at 10(-7) and 10(-6)M with apparent pA2 values of 7.5 and 8.1, respectively. It is suggested that amosulalol at 10(-6)M may have an action additional to beta 1-adrenoreceptor antagonism on the right ventricle. The contractile responses of the rat aorta to phenylephrine were inhibited by amosulalol at 10(-7) and 10(-6)M with a pA2 of 8.6 which was independent of concentration. Amosulalol also reduced the magnitude of the maximal responses of the aorta to 5-hydroxytryptamine.

An 'affinity' method for preparing polypeptides enriched in the collagen-associated Ehrlich chromogen.

The collagen-associated compound which reacts at room temperature with acid dimethylaminobenzaldehyde (Ehrlichs reagent) also reacts in acid with aryl-diazonium reagents. We have developed a convenient method for isolating polypeptides associated with the Ehrlich chromogen from collagen digests utilizing diazotized arylamino-cellulose supports. These peptides, in which the Ehrlich chromogen is 'labeled' with yellow diazo color, constitute less than 0.5% of the collagen, and have amino acid patterns similar to those around the cross link regions. The chromogen is not identical with pyridinoline, also thought to be a polyvalent cross link.

Effects of urethane-chloralose anaesthesia on respiration in the rat.

1. Respiratory effects were measured in rats during six hours' anaesthesia with urethane and chloralose. 2. One-hundred min from urethane administration, minute ventilation (VE) was minimal, arterial PO2 was low, arterial PCO2 was high; tidal volume (VT) and respiratory frequency (f) were relatively constant; hypercarbic and hypoxic responses were substantial. 3. Between 100 and 400 min from urethane administration, minute ventilation and frequency increased and became more variable, tidal volume remained relatively constant, arterial PO2 rose to 100 mmHg, PCO2 fell to 37 mmHg; hypercarbic sensitivity increased and hypoxic sensitivity decreased. 4. We conclude that the anaesthetic regime produced initial depression of respiration relative to metabolism but without great loss of respiratory chemosensitivity. The respiratory depression was prolonged by increased dosage with urethane and chloralose. 5. The variations between hypercarbic and hypoxic responses confirm that they operate through separate mechanisms.

The effect of lentinan on the in utero foetal development of the rat and on postnatal development of the F1 offspring.

Lentinan, a polysaccharide [(1 leads to 3)-beta-D-glucan], at 0.1, 1.0 and 5.0 mg/kg/day was administered i.v. to rats once daily from day 15 of pregnancy to day 21 post partum. All animals were allowed to deliver their young and selected animals of the F1 generation were retained without further treatment, to provide F2 offspring. Reactions to treatment were generally dose-related and included bruising of the tail and swelling and discolouration of the pinnae. Animals at 5.0 mg/kg/day sometimes showed swollen hind limbs and cutaneous lesions of the tail. Mean spleen weight in females was increased at all dosages, more so at 1.0 and 5.0 mg/kg/day. There was no evidence of an adverse effect on litter characteristics, including the pre-weaning development of the F1 offspring, or that treatment of the F0 parents adversely affected post-weaning development and reproductive performance of the F1 offspring.