Biomedical subjects

S A Balogh

Publications and source records attributed to S A Balogh.

15 recordsLinked to original sources

PubMed2001

Facilitated stimulus-response associative learning and long-term memory in mice lacking the NTAN1 amidase of the N-end rule pathway.

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. Inactivation of the NTAN1 gene encoding the asparagine-specific N-terminal amidase in mice results in impaired spatial memory [26]. The studies described here were designed to further characterize the effects upon learning and memory of inactivating the NTAN1 gene. NTAN1-deficient mice were found to be better than wild-type mice on black-white and horizontal-vertical discrimination learning. They were also better at 8-week Morris maze retention testing when a reversal trial was not included in the testing procedures. In all three tasks NTAN1-deficient mice appeared to use a strong win-stay strategy. It is concluded that inactivating the asparagine-specific branch of the N-end rule pathway in mice results in impaired spatial learning with concomitant compensatory restructuring of the nervous system in favor of non-spatial (stimulus-response) learning.

Amidohydrolases↗

PubMed2000

Avoidance learning in autoimmune mice.

Previous studies have shown that autoimmune mice perform very poorly on active avoidance learning tasks. In the current studies, mice with lupus-like systemic autoimmunity were able to learn active, as well as passive, avoidance protocols with shock as reinforcement. Therefore, the behavioral deficits seen in active avoidance tasks are not a consequence of the use of electric shock. Rather, the current findings suggest that the inability of autoimmune mice to learn shock motivated responding is due to multiple performance factors, including shock level and properties of the testing apparatus.

Animals↗

PubMed2000

Spatial ability of XY sex-reversed female mice.

Perinatal gonadal hormones significantly affect subsequent sex differences in reproductive and non-reproductive behaviors in rodents. However, the influence of the sex chromosomes on these behaviors has been largely ignored. To assess the influence of the non-pseudoautosomal region of the Y chromosome, C57BL/JEi male and female mice and mice from the C57BL/6JEi-Y(POS) consomic strain were given behavioral tests known to distinguish males from females. The C57BL/6JEi-Y(POS) strain contains sex-reversed XY-females which, when compared to their XX-female siblings, allow assessment of the influence of the Y chromosome in a female phenotype. XX-females and XY-females did not differ on open-field activity, the Lashley maze, or active avoidance learning, but XY-females were significantly better than XX-females on the Morris hidden platform spatial maze. These findings suggest that males may have both a genetic and a hormonal mechanism to ensure visuospatial superiority.

Animals↗

PubMed2000

Altered activity, social behavior, and spatial memory in mice lacking the NTAN1p amidase and the asparagine branch of the N-end rule pathway.

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. N-terminal asparagine and glutamine are tertiary destabilizing residues, in that they are enzymatically deamidated to yield secondary destabilizing residues aspartate and glutamate, which are conjugated to arginine, a primary destabilizing residue. N-terminal arginine of a substrate protein is bound by the Ubr1-encoded E3alpha, the E3 component of the ubiquitin-proteasome-dependent N-end rule pathway. We describe the construction and analysis of mouse strains lacking the asparagine-specific N-terminal amidase (Nt(N)-amidase), encoded by the Ntan1 gene. In wild-type embryos, Ntan1 was strongly expressed in the branchial arches and in the tail and limb buds. The Ntan1(-/-) mouse strains lacked the Nt(N)-amidase activity but retained glutamine-specific Nt(Q)-amidase, indicating that the two enzymes are encoded by different genes. Among the normally short-lived N-end rule substrates, only those bearing N-terminal asparagine became long-lived in Ntan1(-/-) fibroblasts. The Ntan1(-/-) mice were fertile and outwardly normal but differed from their congenic wild-type counterparts in spontaneous activity, spatial memory, and a socially conditioned exploratory phenotype that has not been previously described with other mouse strains.

Amidohydrolases↗

PubMed1999

A behavioral and neuroanatomical assessment of an inbred substrain of 129 mice with behavioral comparisons to C57BL/6J mice.

The inbred 129 substrains have been characterized as poor learners that display hypoplasia of the corpus callosum. However, they are used extensively as a source of embryonic stem (ES) cells for creating mice carrying altered copies of a targeted gene ('knockout mice'). The present research investigated callosal agenesis and behavior in the 129/SvEvTac substrain and compared their behavior to that of C57BL/6J mice. In addition, the degree to which callosal agenesis affected behavior was assessed. Nearly 80% of 129/SvEvTac mice in the current sample exhibited callosal hypoplasia, although this was not subsequently found to be associated with any measure of cognition. They learned the Morris maze and a non-spatial pattern discrimination task, though at a level inferior to C57BL/6J mice. They were unable to learn shuttlebox avoidance or the Lashley III maze. The only measure on which they performed better than C57BL/6J mice was a simple water escape task. Thus, 129/SvEvTac mice, in addition to displaying aberrant neuroanatomy, perform poorly on many behavioral tasks, resulting in potential interpretational difficulties.

Agenesis of Corpus Callosum↗

PubMed1998

Effects of neocortical ectopias upon the acquisition and retention of a non-spatial reference memory task in BXSB mice.

BXSB mice have a 40-60% incidence of small, focal, neocortical dysplasias called ectopias. Ectopics and non-ectopics were compared on horizontal-vertical discrimination learning, a non-spatial cognitive task. No differences were found during acquisition. Ectopic mice, however, were superior when retested 8 weeks later. The results support prior findings that ectopic mice have better long-term spatial memory and extend this conclusion to the non-spatial domain.

Animals↗

PubMed1998

Ketamine blocks a conditioned taste aversion (CTA) in neonatal rats.

These experiments explored the effects of glutamate, N-methyl-D-aspartate (NMDA) receptor blockade on the formation, retention, and expression of conditioned taste aversion (CTA) in young rats. Previous data from our laboratory suggested that ketamine administration potentiates a CTA in E18 rat fetuses. The current studies investigated this phenomenon in neonates. High-pressure liquid chromatography (HPLC) methods were used to determine the amount of ketamine that must be injected intraperitoneally (i.p.) to achieve brain ketamine levels in neonates comparable to those found in the fetuses from our previous experiments. Then, on their day of birth, Sprague-Dawley rat pups received injections of either 0.1, 10, or 70 mg/kg of ketamine HCI, i.p. or a Sal control injection. One-half hour later, pups were injected orally with either Saccharin (Sac; 10 microL of 0.3%) or water followed by an injection of either lithium chloride (LiCl; 81 mg/kg) or Sal (i.p.). The CTA was evaluated in two different tests. Two weeks after conditioning, the dam was anesthetized and the frequency with which pups attached to Sac-painted nipples versus nipples painted with water was measured (i.e., the nipple taste test, NTT). Controls for state-dependent learning were run in which 10 mg/kg of ketamine or saline (Sal) was administered before both taste aversion conditioning and the NTT. After weaning, the CTA was also evaluated by measuring the amount of Sac (0.3%) or water consumed during a two-bottle test. Neonates that received Sal control injections before the Sac + LiCl pairing acquired CTAs and avoided Sac-painted nipples. However, the pups injected with ketamine on the conditioning day only (P0) did not avoid Sac-painted nipples (as compared to controls). Pups that had ketamine both at the time of CTA training and testing, or just before the NTT, also failed to avoid Sac-painted nipples. Ketamine's acute effects apparently influenced the outcome of the NTT of state-dependent control subjects. Rat pups that received the highest doses of ketamine (10 or 70 mg/kg) and tasted Sac on P0 later failed to show a neophobia for Sac-painted nipples. Whereas, rat pups that received the high dose of ketamine and water on P0, later exhibited a neophobic response. These data suggest that ketamine did not impair the animal's ability to taste Sac. These data reflecting a ketamine-induced blockade of neonatal CTAs may be contrasted with our previous findings in which ketamine potentiated fetal CTAs. However, they are in consonance with data from adult rats suggesting that ketamine can cause an amnesia for CTAs. NMDA receptor blockade may shape memory formation in a manner that is dependent on the stage of brain development.

Animals↗

PubMed1989

Bleeding patterns and acceptability among Norplant users in two Asian countries.

Changes in menstrual bleeding patterns are the most frequent reason for discontinuing NORPLANT during the first year of use. Although NORPLANT is used by more women in Asia than in any other region, the changes that occur among these women are not well documented. In pre-introductory clinical trials of NORPLANT in the Philippines and Sri Lanka, 175 women were enrolled with greater than 95% continuing the method after one year. Daily menstrual bleeding calendars were kept by 94% of subjects for nine months and by 66% for one year. In contrast to findings in previous studies which showed that approximately 60% of NORPLANT users had bleeding disruptions in the first year of use, almost all of these women experienced bleeding disruptions. In a one-year study of menstrual pattern changes, increased bleeding was found to occur with the same frequency as reduced bleeding. However, the changes experienced by the Asian women tended to be decreases, rather than increases, in menstrual bleeding.

Adult↗

PubMed1986

Heart disease in workers exposed to dinitrotoluene.

To determine whether the carcinogenicity of dinitrotoluene (DNT) in rodent bioassays was predictive for humans, we examined the mortality experience of exposed workers at two ammunition plants. Cohorts of 156 and 301 men who had worked a month or more during the 1940s and 1950s at jobs with opportunity for substantial DNT exposure were followed through the end of 1980. Numbers of expected deaths and standardized mortality ratios (SMRs) were computed, using mortality rates of US white males as the standard. No evidence of a carcinogenic effect was found, but unsuspected excesses of mortality from ischemic heart disease were noted at both plants (SMRs) 131 and 143; 95% confidence limits 65 to 234 and 107 to 187, respectively). Deaths from ischemic heart disease remained high even when compared with expected numbers derived using mortality rates of the counties in which the plants were located. Additional analyses revealed evidence of a 15-year latent period and suggested a relationship with duration and intensity of exposure. Epidemiologic investigations of other heavily exposed populations are needed to confirm the etiologic significance of the association between DNT and heart disease described here.

Coronary Disease↗

PubMed1983

Previous abdominal surgery as a risk factor in interval laparoscopic sterilization.

Previous abdominal surgery has been termed a relative contraindication for laparoscopic sterilization. This study quantifies the relative risks of surgical difficulties, immediate complications, and early follow-up complications/complaints of interval sterilization in women with versus women without previous abdominal surgery (PAS and NPAS groups, respectively). This multicenter study included women sterilized by electrocoagulation, the tubal ring, and the spring-loaded clip. Within each center the PAS and NPAS women were generally similar with respect to sociodemographic variables and preexisting medical conditions. Stratified analysis determined that the rate of surgical difficulties was significantly higher in PAS women (relative risk = 2.3, P less than 0.05), but most of these difficulties were overcome without resorting to another technique or approach. The rates of complications as well as the mean operation times and mean durations of hospitalization (indices of medical costs) did not differ significantly between the PAS and NPAS groups.

Abdomen↗

PubMed1983

Vacuum aspiration with the IPAS Modified Gynecologic Syringe.

The IPAS Modified Gynecologic Syringe was compared with the electric pump and standard hand pump in a clinical trial of 1227 women undergoing vacuum aspiration. This modified double-valve syringe was designed to fit larger 8 mm, 10 mm and 12 mm cannulae, which are more suitable for late first trimester procedures. The study was conducted at four centers in which the double-valve syringe was used alternately with the vacuum source normally used at each clinic. Although there were notable inter-center differences with respect to certain outcome variables, results were similar for procedures performed at the same center. The only significant finding was the lower proportion of women requiring D & C to complete uterine evacuation among double-valve syringe patients than among hand pump cases at one center. The data indicate that the double-valve syringe is safe and effective for uterine aspiration in women up to 14 weeks' gestation and may be preferable for use in clinics with limited facilities.

Abortion, Induced↗

PubMed1981

A method for monitoring the fertility of workers. 2. Validation of the method among workers exposed to dibromochloropropane.

A method has been developed for monitoring industrial workers and others exposed to environmental agents which may impair fertility. National birth probabilities specific for maternal birth cohort, age, parity, and race are used to derive expected fertility. Observed fertility is obtained by questionnaire. Standardized fertility ratios are computed for exposure and non-exposure periods and compared. The analytic techniques have been validated by applying the method to a group of 36 male factory employees working in an agricultural chemical division (ACD) where pesticides including the nematocide dibromochloropropane were formulated. Twelve of these employees in mid-1977 had been discovered to have severely depressed sperm counts related to occupational exposure. The standardized fertility ratio (SFR) computed from data available in mid-1977 for the period at risk from employment in the ACD (SFR = 0.75) was significantly lower than those derived for the entire not-at-risk period (SFR = 1.88) and the portion related to employment in other areas of the factory (SFR = 2.16). Similar differences also were evident from data available several years earlier, demonstrating that the surveillance technique would have been capable of detecting occupationally induced infertility among these workers in advance of the actual discovery date.

Antinematodal Agents↗

PubMed1980

A method for monitoring the fertility of workers. 1. Method and pilot studies.

A method has been developed for monitoring male and female industrial workers and other persons exposed to environmental agents which may impair fertility. The essential feature of the method is its ability to distinguish the potential effects of occupational exposure from a multitude of other factors known to affect fertility. Information is collected primarily through use of a questionnaire which take less than three minutes to complete and can be administered to persons of either sex. The advantages and limitations of the method are considered in the context of pilot studies at two small chemical plants and of a review of attempts to assess occupational effects of fertility from interviews of health records.

Environmental Exposure↗

PubMedDate not supplied

Varying intertrial interval reveals temporally defined memory deficits and enhancements in NTAN1-deficient mice.

The N-end rule is one ubiquitin-proteolytic pathway that relates the in vivo half-life of a protein to the identity of its N-terminal residue. NTAN1 deamidates N-terminal asparagine to aspartate, which is conjugated to arginine by ATE1. An N-terminal arginine-bearing substrate protein is recognized, ubiquitylated by UBR1/E3alpha, and subsequently degraded by 26S proteasomes. Previous research showed that NTAN1-deficient mice exhibited impaired long-term memory in the Lashley III maze. Therefore, a series of studies, designed to assess the role of NTAN1 in short- and intermediate-term memory processes, was undertaken. Two hundred sixty mice (126 -/-; 134 +/ +) received Lashley III maze training with intertrial intervals ranging from 2-180 min. Results indicated that inactivation of NTAN1 amidase differentially affects short-, intermediate-, and long-term memory.

Amidohydrolases↗

PubMedDate not supplied

Evaluation of safety, efficacy, and acceptability of NORPLANT implants in Sri Lanka.

This paper presents findings based on a one-year pre-introductory clinical investigation concerning safety, efficacy, and acceptability of the new contraceptive NORPLANT implants in Sri Lanka. The study is based on 400 acceptors of the implants at two clinics in Sri Lanka. Acceptors' mean age was 27 years, mean number of children was about two, and average educational attainment was eight years. Nearly half of the acceptors did not want to have another child. Follow-up was conducted at one, three, six, and twelve months. The one-year termination rate due to medical problems was very low, and the one-year life-table pregnancy rate was 0.5. Menstrual pattern disruption was the most frequently reported complaint with the implants. Amenorrhea increased in the first three months of use, and intermenstrual bleeding was common among those menstruating. In spite of these changes and some significant variations between the acceptors in the two study center, the overall degree of satisfaction with the implants was very high. The features most important to the acceptability of the implants were low risk of pregnancy, the long duration of action, and the convenience of use. The results of the study suggest that NORPLANT implants are safe, effective, and highly acceptable to Sri Lankan women.

Adolescent↗