First Observation of P-odd γ Asymmetry in Polarized Neutron Capture on Hydrogen.

We report the first observation of the parity-violating gamma-ray asymmetry A_{γ}^{np} in neutron-proton capture using polarized cold neutrons incident on a liquid parahydrogen target at the Spallation Neutron Source at Oak Ridge National Laboratory. A_{γ}^{np} isolates the ΔI=1, ^{3}S_{1}→^{3}P_{1} component of the weak nucleon-nucleon interaction, which is dominated by pion exchange and can be directly related to a single coupling constant in either the DDH meson exchange model or pionless effective field theory. We measured A_{γ}^{np}=[-3.0±1.4(stat)±0.2(syst)]×10^{-8}, which implies a DDH weak πNN coupling of h_{π}^{1}=[2.6±1.2(stat)±0.2(syst)]×10^{-7} and a pionless EFT constant of C^{^{3}S_{1}→^{3}P_{1}}/C_{0}=[-7.4±3.5(stat)±0.5(syst)]×10^{-11} MeV^{-1}. We describe the experiment, data analysis, systematic uncertainties, and implications of the result.

Protein design of an HIV-1 entry inhibitor.

Human immunodeficiency virus type-1 (HIV-1) membrane fusion is promoted by the formation of a trimer-of-hairpins structure that brings the amino- and carboxyl-terminal regions of the gp41 envelope glycoprotein ectodomain into close proximity. Peptides derived from the carboxyl-terminal region (called C-peptides) potently inhibit HIV-1 entry by binding to the gp41 amino-terminal region. To test the converse of this inhibitory strategy, we designed a small protein, denoted 5-Helix, that binds the C-peptide region of gp41. The 5-Helix protein displays potent (nanomolar) inhibitory activity against diverse HIV-1 variants and may serve as the basis for a new class of antiviral agents. The inhibitory activity of 5-Helix also suggests a strategy for generating an HIV-1 neutralizing antibody response that targets the carboxyl-terminal region of the gp41 ectodomain.

Iron status of middle-aged women in five counties of rural China.

OBJECTIVE: To determine the relationships of dietary iron sources, other dietary factors, and lifestyle to iron status among premenopausal and recently postmenopausal Chinese women with widely varying regional dietary patterns. DESIGN: Cross-sectional. Subjects were interviewed, blood samples were drawn, and dietary intakes were measured by a 3-day dietary survey for subjects in the five survey counties. SETTING: Rural China. SUBJECTS: About 80 randomly selected subjects per county among women aged 32 66 y. MAIN OUTCOME MEASURES: Blood hemoglobin, plasma ferritin, and plasma iron. RESULTS: Total iron intake was relatively high (15-29 mg/d) compared to developed counties. Heme iron intake was negligible in two of the study counties. Overall levels of iron deficiency anemia were relatively low in these generally iron-stressed women. There was no clear statistical relationship between iron intake and physiological iron status. Although several measures of dietary intake (heme iron, dietary calcium, animal protein) were correlated with several measures of iron status before adjusting for survey county, only dietary animal protein was significantly positively correlated with plasma ferritin after adjusting for the possibly confounding factor of the survey county (r= 0.15, P = 0.009). Intakes of potential inhibitors of iron absorption, such as tea, even in very high amounts, were not correlated to iron status. Plasma ferritin was positively correlated with plasma retinol (P = 0.024) and cholesterol (P = 0.007). Systemic inflammatory response, as indicated by high plasma C-reactive protein levels, was shown to be raised in a group of subjects with apparently contradictory high levels of ferritin and low levels of hemoglobin (P = 0.03). CONCLUSIONS: Iron nutriture in these areas of rural China seemed more related to physiological factors such as inflammatory response, menses, plasma vitamin A and cholesterol, than to dietary factors.

Determinants of plasma retinol concentrations of middle-aged women in rural China.

The purpose of this study was to assess the correlates and possible determinants of plasma vitamin A among middle-aged women in rural China. The vitamin A adequacy of the different diets at the five widely varying survey sites was also assessed. Patterns of correlations among dietary and biochemical measurements were strikingly different from previous studies in Western subjects. Plasma beta-carotene was uncorrelated with beta-carotene intake even after adjusting for potential confounders. In counties with low preformed vitamin A intake, plasma retinol correlated with plasma copper (P = 0.007), which in turn was correlated with dietary intake of copper (P = 0.007). In these counties plasma retinol was correlated with plasma beta-carotene (P = 0.001) and was increased 10% in women in the first 2 y of menopause (P = 0.028). Plasma retinol and C-reactive protein levels are inversely correlated (r = -0.15, P < 0.001), indicating that vitamin A status and inflammatory response may be related but the causal direction is unknown. Despite low intake of vitamin A (county averages of 13-78% of recommended daily allowance [RDA]), and particularly of preformed vitamin A, only 3% of these women had plasma retinol levels below 0.7 mumol/L, considered to indicate possible marginal deficiency. Plasma levels of retinol and beta-carotene were more influenced by intrinsic factors such as menopause, lipid status, retinol requirements, and possibly copper status and inflammation than by extrinsic factors such as diet and lifestyle.

Experiences and processes affecting racial identity development: preliminary results from the biracial sibling project.

Siblings of mixed racial heritage often identify differently from one another. In a study of 20 sibling pairs, 4 types of experiences surfaced that appear to influence the identity process: hazing, family dysfunction, other salient identities, and the impact of integration. These experiences were explored within the framework of the ecological model of racial identity development.

Dissimilarity in aflatoxin dose-response relationships between DNA adduct formation and development of preneoplastic foci in rat liver.

Earlier work in this laboratory and that carried out by others demonstrated that after a single dose of aflatoxin B1 (AFB) the resulting liver AFB-DNA adduct levels were directly proportional to dose. Earlier work also showed that after ten daily doses the AFB dose-response relationship with gamma-glutamyl transpeptidase (GGT) positive preneoplastic foci measured at 3 months was sublinear, with a threshold at a dose of about 150 micrograms/kg body weight/day. The objective of this study is to determine the factors influencing the shift in AFB dose-response between AFB-DNA adducts and GGT foci. Male Fisher 344 weanling rats were orally administered one or ten doses of AFB ranging from 50 to 350 micrograms/kg body weight/day. The animals were killed 2 or 24 h after the first AFB dose, or after the tenth AFB dose. The first and tenth doses were tritiated in these animals and 3H-AFB-guanine adducts isolated from liver DNA were measured by HPLC. Another group was killed 3 months after receiving ten doses in order to measure GGT foci development. AFB-guanine adduct levels were directly proportional to dose after the first dose, but after the tenth dose were much lower in the 200-350 micrograms/kg groups than after a single dose. The GGT foci response confirmed earlier work concerning a sublinear response. Among the individual animals in the 200-350 micrograms/kg groups there was a positive relationship, after controlling for dose, between GGT foci development and weight gained both during dosing (P = 0.018) and also to a lesser extent during the early promotional period (P = 0.066). Enzyme activity levels of GGT in liver homogenates were higher in the highest dose groups and reflected biliary proliferation rather than histological GGT stained foci. Urinary levels of AFB metabolites changed proportions in the high dosage multiply dosed animals reflecting alteration in AFB metabolism or excretion. The differences between the linear adduct and the sublinear foci dose-response curves may be the result of non-adduct effects of higher multiple AFB doses on foci formation including acute cytotoxicity, altered AFB metabolism and disposition, enhanced weight gains, or shortened foci latency but not through enhanced guanine adduct levels. Other studies that showed a linear relationship between AFB dose and liver tumor development used continuous feeding of maximal doses an order of magnitude less than the lowest dose in this study and thus avoided acutely toxic effects. We hypothesize that liver tumor development may mirror foci response in a 10-dose AFB regimen with doses above 100 micrograms/kg due to acute toxicity effects.

Use of an improved method for analysis of urinary aflatoxin M1 in a survey of mainland China and Taiwan.

An improved monoclonal antibody immunoaffinity chromatography/high-pressure liquid chromatography/ fluorescence detection method was developed to measure aflatoxin (AF) exposure by quantifying AFM1 in human and rat urine samples. Analysis of different amounts of various AF metabolites showed that the immunoaffinity resin was highly selective for aflatoxin B1 (AFB1), AFB2, and AFM1. Recovery of added AFs increased with the amount of immunoaffinity resin and was virtually complete within the range of 0.01-10 ng of AFM1 by using 7 ml of resin. The detection limit of this method is 0.5 pg/ml urine. Rats dosed with tritiated AFB1 excreted in their urine tritiated AFM1, among other AF metabolites, as indicated by chemical derivative confirmation and cochromatography with authentic AFM1 and agreement of radioactivity and fluorescence quantitation. A linear dose-response relationship was found over the range of 0.05-50 micrograms/kg of body weight/day. Two humans dosed with 1.0 microgram of pure AFB1 excreted 6-7% of the dose as urinary AFM1 over 5-7 days. Pooled urine samples from 30 men from each of 69 rural counties in mainland China and 16 survey areas in Taiwan, with two villages per county or area, were analyzed with this improved method (170 villages total). The correlation coefficient of urinary excretion of AFM1 compared between villages within all 85 survey areas was 0.50 (P < 0.001). Sixty-five % of the samples contained detectable concentrations of AFM1 with an average excretion of 3.1 ng/12 h. Assuming an excretion rate of 2-6%, this AFM1 excretion corresponds to a very low average daily AF consumption of 0.1-0.3 microgram/day (possible range, 0-11 micrograms/day). Patterns of urinary excretion of AFM1 were similar in mainland China and Taiwan.

The effect of prepuberal and postpuberal gonadectomy on radial physeal closure in male and female domestic cats.

Male (n = 6/group) and female (n = 6/group) kittens were gonadectomized at 7 weeks (prepuberally) or 7 months of age (postpuberally), or left intact. Lateral radiographic projections of the right forelimb were made from 4 months of age until the distal radial physis was closed, or 24 months of age. In males, distal radial physeal closure was delayed in both groups of gonadectomized animals, compared to intact males (p < 0.01). In females, proximal radial physeal closure was significantly delayed in prepuberally gonadectomized animals (p = 0.02), and distal radial physeal closure was significantly delayed in both groups of gonadectomized animals, compared to intact animals (p < 0.01). Final radial length (females p < 0.01, males p = 0.01), and age and radial length at time of the growth plateau (p < 0.01) were significantly increased in all gonadectomized animals. Age at gonadectomy had no effect on age and radial length at time of the growth plateau. No puberal growth spurt was observed in any of the cats.

Effects of carotenoid-rich food extracts on the development of preneoplastic lesions in rat liver and on in vivo and in vitro antioxidant status.

The effect of dietary carotenoid-rich extracts of carrots, tomatoes, and orange juice on rat liver gamma-glutamyl transpeptidase-positive preneoplastic foci induced by aflatoxin B1 was investigated. Organic extracts were prepared from the foods, dissolved in tricaprylin oil to equivalent concentrations of the major food-specific carotenoids, and fed by intubation to Fischer 344 male rats. The extracts were administered during the 2-week aflatoxin-dosing (initiation) period of the study or during the subsequent 12-week post-dosing (promotion) period. Vitamin status and antioxidant activities were measured in blood and liver. Extract feeding caused an accumulation of carotenoids in the liver, a substantial decrease in spontaneous erythrocyte hemolysis, and lowered plasma glutathione, blood superoxide dismutase, and blood catalase. Differences in foci development among the three extracts were not as consistent or profound as differences between initiation and promotion dosing. The number of gamma-glutamyl transpeptidase-positive foci was decreased by extract feeding during the initiation period, whereas extract feeding during the promotion period caused a decrease in the average diameter of the foci. The total volume of foci was markedly reduced by extract feeding during either period. Extracts were compared with purified carotenoids and alpha-tocopherol in their ability to affect in vitro antioxidation activity and were nearly as effective as the pure compounds. In summary, carotenoid-rich extracts of these three foods substantially inhibited biochemical and cellular events thought to play a role in the early stages of hepatocarcinogenesis.

Vitamin A and carotenoid status in rural China.

Vitamin A status of 260 groups of twenty-five males or twenty-five females, aged 35-64 years, surveyed in twenty-four provinces of the People's Republic of China, was assessed by measuring plasma retinol. retinol-binding protein and beta-carotene concentrations. Direct measurements of food intake over a 3 d period and questionnaire data on the frequency of consumption of vegetables, fruits, animal products and other dietary items were also used. Vitamin A status appeared to be low only in specific counties but in general was satisfactory or only marginally deficient. Plasma beta-carotene levels were strikingly low in comparison with Western levels despite generous vegetable consumption suggesting that intake of vitamin A precursors may have been adequate but not abundant enough to maintain high circulating plasma levels of beta-carotene. Plasma beta-carotene, for both males and females, was significantly correlated with the frequency of consumption of green vegetables. Plasma retinol, for males, was highly correlated with meat, fish, oil and alcohol consumption expressed both in quantity or frequency of consumption. Higher levels of plasma retinol, together with lower levels of plasma beta-carotene in males compared with females, suggest that men consume more animal products or may have higher retinol requirements and therefore a higher rate of conversion of beta-carotene to retinol.

Intestinal pseudodiverticulosis in a cat.

A two-year-old domestic shorthair presented for estrous behavior four months after ovariohysterectomy. On exploratory laparotomy, ovarian remnant tissue and multiple intestinal diverticula were found. Histopathology identified the diverticula as pseudodiverticula.

Effect of prepuberal and postpuberal gonadectomy on heat production measured by indirect calorimetry in male and female domestic cats.

OBJECTIVE: To use indirect calorimetry to compare heat production between gonadectomized and sexually intact male and female cats. DESIGN: Male (n = 6) and female (n = 6) kittens were gonadectomized at 7 weeks or 7 months of age, or left sexually intact. Body heat production was measured by indirect calorimetry in all cats at 12, 18, and 24 months of age. ANIMALS: 18 male and 18 female clinically normal domestic shorthair cats. PROCEDURE: Heat production was measured, using an open-circuit, respiratory, indirect calorimeter. All cats underwent calorimetry at 12, 18, and 24 months of age. The heat coefficient, a measure of resting metabolic rate, was calculated for each cat at each test; heat coefficient is defined as logarithm of heat (kcal/h) divided by logarithm of body weight (kg). RESULTS: Heat production did not vary with age in male or female cats. Heat coefficient was higher in sexually intact male and female cats than in gonadectomized male and female cats at 12, 18, and 24 months of age (12 months, females, P < 0.01, males, P = 0.04; 18 months, females, P < 0.01, males, P = 0.02; and 24 months, females and males, P < 0.01). CONCLUSIONS: These data suggest that resting metabolic rate in cats decreases after gonadectomy. CLINICAL RELEVANCE: A decrease in metabolic rate is synonymous with a decrease in caloric requirements. Gonadectomized animals fed in a manner similar to sexually intact animals may be predisposed to obesity and its sequelae.

Estrous length, pregnancy rate, gestation and parturition lengths, litter size, and juvenile mortality in the domestic cat.

Reproductive performance in a feline research colony of 14 queens is reported. Average estrous length in 38 cycles was 5.8 +/- 3.3 days, with a range of two to 19 days. Estrous length in 23 bred cycles was not shorter (p greater than 0.05) than in 15 nonbred cycles, suggesting that induction of ovulation does not decrease estrous length. Pregnancy rate in 23 bred cycles was 73.9%. Gestation length averaged 66.9 +/- 2.9 days with a range of 62 to 71 days (n = 15). Average parturition length was 16.1 +/- 14.3 hours (n = 7), with a range of four to 42 hours. Litter size ranged from one to five kittens, with an average of 3.7 kittens per litter (n = 15). Percent mortality by eight weeks of age was 29.1%, with 4.7% stillbirths.

Diabetes mellitus associated with pancreatic endocrine insufficiency in a kitten.

Diabetes mellitus, characterised by persistent hyperglycaemia and glucosuria, was diagnosed in a six-week-old kitten. Pancreatic sections contained low numbers of atypically small islets and immunohistochemistry demonstrated pancreatic endocrine insufficiency with virtually no production of any islet hormones. There was no inflammatory infiltration of the islets, as seen in the form of diabetes mellitus characteristic of juvenile humans.

Vaginal septa in dogs: 15 cases (1983-1992).

Medical records of 15 dogs with vaginal septa, examined between April 1983 and December 1992, were reviewed. Overall prevalence of vaginal septation at the hospital during the study period was 0.03%. Thirteen breeds were represented; mean age at the time of initial examination was 2.4 years. Owners' original complaints included inability to breed naturally, dysuria, urinary incontinence, infertility, recurrent vaginitis, ambiguous external genitalia, and dystocia. One dog did not have clinical signs associated with the vaginal septum. In 11 of the 15 dogs, the septum could be palpated during digital vaginal examination. The septum could be seen in 6 of the 7 dogs in which vaginoscopy was performed. Twelve of the 15 dogs underwent positive-contrast vaginography; in all 12, the septum could be easily seen. Four of the 15 dogs underwent removal of the septum, with or without episiotomy, and 4 others were ovariohysterectomized. One dog was bred by means of artificial insemination and became pregnant. The remaining 6 dogs were lost to follow-up.

Two identical noninteracting sites in an ion channel revealed by proton transfer.

The functional consequences of single proton transfers occurring in the pore of a cyclic nucleotide-gated channel were observed with patch recording techniques. These results led to three conclusions about the chemical nature of ion binding sites in the conduction pathway: The channel contains two identical titratable sites, even though there are more than two (probably four) identical subunits; the sites are formed by glutamate residues that have a pKa (where K(a) is the acid constant) of 7.6; and protonation of one site does not perturb the pKa of the other. These properties point to an unusual arrangement of carboxyl side-chain residues in the pore of a cation channel.

Development of the functional orthosis.

In conclusion, a functional orthosis may be used to effectively treat most, but not all, abnormalities of the lower extremity that cause abnormal function of the foot. Abnormalities that are resistant to treatment with functional orthoses are compensated talipes equinus, excessive verticality of the oblique axis of the midtarsal joint, forefoot adductus that exceeds 15 degrees of adductus, Charcot's disease, congenital shortage of the iliopsoas muscle, and certain neurologic diseases that exhibit transient muscle spasm or paralysis, resulting in abnormal forces acting upon the foot that vary with time. Unfortunately, laboratories that claim to fabricate functional orthoses may turn out products that vary from nondescript arch supports to orthoses that only partially control function of the foot. The author hopes the practitioner who reads this article will be better able to evaluate whether his or her laboratory is providing his or her patient with a functional orthosis when one is ordered.