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Biomedical subjects

B L Williams

Publications and source records attributed to B L Williams.

At least 37 records · Page 2Linked to original sources
PubMed1996

Sequential involvement of Lck and SHP-1 with MHC-recognizing receptors on NK cells inhibits FcR-initiated tyrosine kinase activation.

Recognition of major histocompatibility (MHC) class I complexes on target cells by killer cell inhibitory receptors (KIR) blocks natural killer (NK) and T cell cytotoxic function. The inhibitory effect of KIR ligation requires the phosphotyrosine-dependent association of KIR with the cytoplasmic SH2-containing protein tyrosine phosphatase SHP-1. Using a somatic genetic model, we first define a requirement for the Src family protein tyrosine kinase (PTK) Lck in mediating KIR tyrosine phosphorylation. We then investigate how KIR ligation interrupts PTK-dependent NK cell activation signals. Specifically, we show that KIR ligation inhibits the Fc receptor (FcR)-induced tyrosine phosphorylation of the FcR-associated zeta signaling chain, the PTK ZAP-70, and phospholipase C gamma. Overexpression of catalytically inactive SHP-1 (acting as a dominant negative) restores the tyrosine phosphorylation of these signaling events and reverses KIR-mediated inhibition of NK cell cytotoxic function. These results suggest sequential roles for Lck and SHP-1 in the inhibition of PTK following MHC recognition by NK cells.

Amino Acid Sequence↗
PubMed1995

Tissue plasminogen activator induction in Purkinje neurons after cerebellar motor learning.

The cerebellar cortex is implicated in the learning of complex motor skills. This learning may require synaptic remodeling of Purkinje cell inputs. An extracellular serine protease, tissue plasminogen activator (tPA), is involved in remodeling various nonneural tissues and is associated with developing and regenerating neurons. In situ hybridization showed that expression of tPA messenger RNA was increased in the Purkinje neurons of rats within an hour of their being trained for a complex motor task. Antibody to tPA also showed the induction of tPA protein associated with cerebellar Purkinje cells. Thus, the induction of tPA during motor learning may play a role in activity-dependent synaptic plasticity.

Animals↗
PubMed1995

Characterization of the human XPA promoter.

We cloned the human xeroderma pigmentosum group A gene (XPA) and characterized the XPA promoter (pXPA) by transient cat expression. The pXPA is extraordinarily weak in human fibroblasts (1% of RSV-LTR) and appears to function without any of the usual promoter elements. Regions containing positive and negative control elements were localized.

Base Sequence↗
PubMed1995

Increasing xylazine dose-enhanced anesthetic properties of telazol-xylazine combination in swine.

We evaluated combinations of telazol, ketamine, and xylazine (TKX), telazol and xylazine (TX), telazol, xylazine, and xylazine (T2X), and ketamine and xylazine (KX) for chemical restraint and anesthesia induction in swine. Forty healthy mixed-breed pigs were randomly assigned to the four treatment groups with 10 pigs in each group. For TKX, TX, and T2X combinations, anesthetics were premixed by adding xylazine and ketamine, sterile water and xylazine, or xylazine alone directly into the telazol vial. For KX, anesthetic agents were drawn up separately, then mixed in the same syringe immediately before injection. All anesthetics were given as a single intramuscular injection. All four anesthetic combinations induced a rapid onset of sternal recumbency within 1.55 +/- 0.5 min and lateral recumbency within 2.27 +/- 0.6 min in pigs after intramuscular injection. There was no significant difference among treatments in these regards. The T2X combination induced a significantly longer duration of analgesia than did either TKX, TX, or KX. The T2X combination also induced a significantly longer duration of tolerance for endotracheal intubation and duration of lateral recumbency. Heart and respiratory rates were not significantly different among the four treatment groups. Vomiting was not observed in any of the treated pigs throughout the procedure. Recovery quality and duration from time of drug administration to recovery of pig walking unassisted were similar in three treatment groups but was shorter in KX-treated pigs. We concluded that all four anesthetic combinations were suitable for chemical restraint but that only TKX, TX, and T2X were suitable for anesthesia induction in pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1994

Expression of a functional human complement inhibitor in a transgenic pig as a model for the prevention of xenogeneic hyperacute organ rejection.

The serious shortage of human organs available for transplantation has engendered a heightened interest in the use of animal organs (xenografts) for transplantation. However, the major barrier to successful discordant xenogeneic organ transplantation is the phenomenon of hyperacute rejection. Hyperacute rejection results from the deposition of high-titer preformed antibodies that activate serum complement on the luminal surface of the vascular endothelium, leading to vessel occlusion and graft failure within minutes to hours. Although endogenous membrane-associated complement inhibitors normally protect endothelial cells from autologous complement, they are species restricted and thus confer limited resistance to activated xenogeneic complement. To address the pathogenesis of hyperacute rejection in xenotransplantation, transgenic mice and a transgenic pig were engineered to express the human terminal complement inhibitor hCD59. High-level cell surface expression of hCD59 was achieved in a variety of murine and porcine cell types, most importantly on both large vessel and capillary endothelium. hCD59-expressing porcine cells were significantly resistant to challenge with high-titer anti-porcine antibody and human complement. These experiments demonstrate a strategy for developing a pig-to-primate xenogeneic transplantation model to test whether the expression of a human complement inhibitor in transgenic pigs could render xenogeneic organs resistant to hyperacute rejection.

Animals↗
PubMed1994

The porcine mammary gland as a bioreactor for complex proteins.

The similar biological activity of rhPC and hPC indicates that porcine mammary gland can perform many of the processing reactions necessary for recombinant synthesis of complex human proteins and produce them at levels suitable for industrial bioreactor applications. The health of the transgenic pigs appeared unaffected by the expression of high levels of the heterologous protein. We suggest that one of the advantages of using the mammary gland as a bioreactor appears to be the high cell density relative to that of cell culture.

Animals↗
PubMed1994

Global intellectual deficits in cystinosis.

Fourteen families of children with infantile nephropathic cystinosis were evaluated using the Stanford-Binet Intelligence Scale, Fourth Edition [Thorndike et al., 1986: Stanford-Binet Intelligence Scale, Fourth Ed.]. The IQs of 15 children with cystinosis, their 23 sibs and 24 parents were compared in order to evaluate a potential effect of cystinosis on intelligence. Children with cystinosis had a significantly lower mean IQ than their sibs and their parents (P = .001). Thus, even though the mean IQ of the children with cystinosis (94.4 +/- 10) was within the average range, there is evidence that these children have a mild global intellectual deficit relative to their expected IQ based upon the IQs of other relatives. In addition, to a subset of the subjects we administered a measure of scholastic ability, the Wide Range Achievement Test-Revised [Jastak and Wilkinson, 1984: The Wide Range Achievement Test-Revised], which consists of spelling, reading, and arithmetic subtests. The 11 cystinosis subjects scored significantly lower (P = .01) than their 16 sibs and their 14 parents in the area of spelling, whereas they did not significantly differ in their performance in the areas of reading and arithmetic.

Absenteeism↗
PubMed1994

A methodological comparison of survey techniques in obtaining self-reports of condom-related behaviors.

To obtain more accurate accounts of sexual attitudes and practices, researchers must explore innovative ways to overcome the reluctance of individuals to disclose sensitive and perhaps incriminating information about themselves. The differences among selected modes of inquiry and survey techniques used to gather self-reports about sensitive contraceptive behaviors among young adults were examined in this study. Comparisons were made between the randomized response versus the direct-inquiry survey techniques and personal interview versus self-administered modes of inquiry relative to the reporting of sensitive condom-related sexual practices of 352 students at a large northeastern university. Findings indicated that the "controlled-choice" randomized-response technique was less effective in obtaining self-reports about condom-related practices than were direct-inquiry techniques. Recommendations for investigations are proposed.

Adolescent↗
PubMed1993

A controlled randomized response technique.

The randomized response survey technique appears to be suitable for studies of sensitive sexual behaviors, particularly in AIDS-related research. However, existing methods provide only estimates of group statistics, not of individual information. Additionally, the popular "unrelated question" approach requires the knowledge of the parameters of the unrelated question. In this article, a variation of the unrelated-question method is suggested for use. Specifically, it is suggested that the unrelated question be one to which the response is known to be "yes." Through this "controlled" approach, the raw data become a direct linear transformation of the response to the sensitive question, and thus can be used directly in regression and other analyses at the individual score level. The estimation of the parameters for the unrelated question is not necessary and the hesitation to provide a "yes" response found in the "forced choice" method is minimized.

Female↗
PubMed1993

Comparison of Telazol, Telazol-ketamine, Telazol-xylazine, and Telazol-ketamine-xylazine as chemical restraint and anesthetic induction combination in swine.

The use of Telazol (T, tiletamine and zolazepam, 4.4 mg T/kg) alone, Telazol-ketamine (TK, 4.4 mg T/kg and 2.2 mg K/kg), Telazol-xylazine (TX, 4.4 mg T/kg, 2.2 mg X/kg), and Telazol-ketamine-xylazine (TKX, 4.4 mg T/kg, 2.2 mg K/kg, and 2.2 mg X/kg) as chemical restraint and anesthetic induction combination was compared in pigs. Forty mixed-breed healthy pigs (24.4 +/- 5.6 kg, mean +/- SD) were randomly assigned to the four treatment groups (T, TK, TX, TKX) with 10 pigs in each group. All the anesthetics were premixed by adding sterile water, ketamine, xylazine, or xylazine and ketamine directly into the Telazol vial and given as a single intramuscular injection. All four anesthetic combinations induced a rapid onset of sternal recumbency within 1.76 +/- 1.0 minutes and lateral recumbency within 3.02 +/- 2.2 minutes in pigs after intramuscular injection; there was no significant difference among treatments. The combinations TX and TKX induced analgesia (as evident by a lack of response to needle prick in the middle portion of the pinna and flank regions) duration of 29.0 +/- 11.0 and 36.0 +/- 12.2 minutes, respectively, and ability to tolerate tracheal intubation (as evident by lack of coughing and chewing response to a laryngoscope) for a period of 34.0 +/- 8.4 and 39.0 +/- 9.9 minutes, respectively. The combinations T and TK did not induce analgesia nor conditions suitable for intubation. Duration of lateral recumbency was 29.9 +/- 10, 33.1 +/- 6.9, 52.2 +/- 6.9, and 61.5 +/- 10.7 minutes in T-, TK-, TX-, and TKX-treated pigs, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia Recovery Period↗
PubMed1992

Evaluation of systems for collection of porcine zygotes for DNA microinjection and transfer.

Crossbred gilts and sows (n=116) were used for the collection of 1-cell zygotes for DNA microinjection and transfer. Retrospectively, estrus synchronization and superovulation schemes were evaluated to assess practicality for zygote collection. Four synchronization and superovulation procedures were used: 1) sows were observed for natural estrous behavior; 1000 IU human chorionic gonadotrophin (hCG) was administered at the onset of estrus (NAT); 2) cyclic gilts were synchronized with 17.6 mg altrenogest (ALT)/day for 15 to 19 days followed by superovulation with 1500 IU pregnant mares serum gonadotropin (PMSG) and 500 IU hCG (LALT); 3) gilts between 11 and 16 days of the estrous cycle received 17.6 mg ALT for 5 to 9 days and PMSG and hCG were used to induce superovulation (SALT); and 4) precocious ovulation was induced in prepubertal gilts with PMSG and hCG (PRE). A total of 505 DNA microinjected embryos transferred into 17 recipients produced 7 litters and 50 piglets, of which 8 were transgenic. The NAT sows had less (P < 0.05) ovarian activity than gilts synchronized and superovulated by all the other procedures. Synchronization treatments with PMSG did not differ (P > 0.05) in the number of corpora hemorrhagica or unovulated follicles, but SALT and PRE treaments had higher ovulation rates than LALT (24.7 +/- 2.9, 24.3 +/- 1.8 vs 11.6 +/- 2.7 ovulations; X +/- SEM). The SALT and PRE treatments yielded 12.3 +/- 2.6 and 17.7 +/- 1.7 zygotes. Successful transgenesis was accomplished with SALT and PRE procedures for estrus synchronization and superovulation.

Journal Article↗
PubMed1992

In vitro development of zygotes from prepubertal gilts after microinjection of DNA.

The effect of pronuclear microinjection of DNA and culture in excised mouse oviducts on the development of porcine zygotes was assessed in this study. Precocious ovulation was induced in prepubertal gilts with pregnant mare's serum gonadotrophin and hCG. Zygotes received either pronuclear microinjection of buffer alone, buffer containing a DNA construct, or no microinjection. Zygotes were cultured in vitro in either modified Krebs-Ringer bicarbonate medium (KRB) for 144 h or in mouse oviduct (MO) explant culture with KRB for 48, 72, 96, or 120 h. Pronuclear microinjection of DNA resulted in a lower (P less than .05) cleavage index (CI) than did buffer or no microinjection (CI 2.16 +/- .10 vs 2.80 +/- .13 and 2.93 +/- .10). The CI loss was greatest for DNA-injected zygotes at the two-cell stage of development. Coculture of zygotes in MO resulted in a higher CI (P less than .01) than did culture in KRB. Culture in MO for 72 h was the most beneficial system compared with MO for 48, 96, or 120 h (P less than .05; CI 3.25 +/- .12 vs 2.66 +/- .18, 2.79 +/- .14, and 2.40 +/- .14, respectively). Microinjection of DNA, not merely the mechanical procedure, was detrimental to early zygote development and may be the cause of low pregnancy rates.

Animals↗
PubMed1992

The effect of day of the estrous cycle, location of ovulatory structure, and progesterone on in vitro bovine endometrial secretions.

Endometrial tissue was collected by biopsy from mature Holstein cows either on d 0 (estrus) or on d 9, 14, or 18 of the estrous cycle to determine the effects of day of the cycle, uterine horn, and in vitro progesterone on endometrial protein secretion. Tissue was incubated for 24 h in supplemented media containing 14C amino acids and either 0, 4.7, or 47 ng of progesterone/ml. Media were analyzed for total protein, radiolabeled protein, and profile of protein released during incubation. Endometrial tissue at d 0 released more protein than did tissue collected on all other days. Radiolabeled proteins were greater on d 0 and 18 than on d 9 and 14. Endometrium from the uterine horn contralateral to the corpus luteum released more radiolabeled protein than endometrium from the uterine horn ipsilateral to the corpus luteum. Seventeen protein bands were identified by electrophoresis. Proximity of the uterine horn to the site of ovulation affected the distribution of specific bands 21,400, 55,000, 74,600, and 88,100 molecular weight. The proportion of released proteins represented by proteins of molecular weights 12,700, 19,100, 21,400, 32,000, and 66,500 was affected either by day of the estrous cycle, proximity of uterine horn to the site of ovulation, or progesterone concentration. The results show that day of the estrous cycle and uterine horn not only alter overall endometrial protein secretion and synthetic activity but also have specific effects on distribution of individual proteins.

Animals↗
PubMed1991

Assessment of behavioral sequelae of traumatic and chemical CNS insult.

Twenty patients with traumatic head injury and 20 patients with neurotoxic chemical exposure completed a 68-item Behavior Inventory listing preinsult versus postinsult behavior presence or absence for each item. Forty controls completed the same inventory, covering approximately the same intervals of time involved with CNS insult group. Whereas controls showed nonsignificant behavior changes on any variable, clinical groups reported significant behavior change on the majority of behavioral variables. There were some differential changes between the two clinical groups. Findings suggest an approach to assessing behavior changes due to CNS insult.

Journal Article↗
PubMed1989

Prevalence of hydrogen peroxide-producing Lactobacillus species in normal women and women with bacterial vaginosis.

A predominance of Lactobacillus species in the vaginal flora is considered normal. In women with bacterial vaginosis, the prevalence and concentrations of intravaginal Gardnerella vaginalis and anaerobes are increased, whereas the prevalence of intravaginal Lactobacillus species is decreased. Because some lactobacilli are known to produce hydrogen peroxide (H2O2), which can be toxic to organisms that produce little or no H2O2-scavenging enzymes (e.g., catalase), we postulated that an absence of H2O2-producing Lactobacillus species could allow an overgrowth of catalase-negative organisms, such as those found among women with bacterial vaginosis. In this study, H2O2-producing facultative Lactobacillus species were found in the vaginas of 27 (96%) of 28 normal women and 4 (6%) of 67 women with bacterial vaginosis (P less than 0.001). Anaerobic Lactobacillus species (which do not produce hydrogen peroxide) were isolated from 24 (36%) of 67 women with bacterial vaginosis and 1 (4%) of 28 normal women (P less than 0.001). The production of H2O2 by Lactobacillus species may represent a nonspecific antimicrobial defense mechanism of the normal vaginal ecosystem.

Cervix Mucus↗
PubMed1988

Relationships between days post partum, observed estrus and uterine microflora in commercial dairy cows.

This study was conducted to determine relationships between the uterine microflora and reproductive characteristics of dairy cows. Uterine lumina were swabbed during estrus immediately prior to artificial insemination (A I). Swabbings were cultured for bacteria and accessed for cytologic evidence of inflammation. The time of sampling averaged 104 d post partum. Bacteria in the uterus were cultured from 65% of the cows (n = 85). The number of cows with any given microbial genus ranged from 1 to 35 and the number of different genera per cow ranged from 0 to 8. There were on significant correlations between amount and type of uterine microflora, days post partum, numbers of observed estrus, conception rate and uterine inflammation. The number of observed estrus periods was not correlated with the presence of aerobic bacteria. No significant relationships were found between microbes and uterine inflammation or conception to the A.I. service at the time of sampling. A negative correlation between uterine inflammation and conception approached significance (r=-0.24, P > 0.10). Acquisition of uterine lumen samples by the technique utilized had no effect on conception to A I service.

Journal Article↗
PubMed1988

Impact of site of inseminate deposition and environmental factors that influence reproduction of dairy cattle.

Uterine body and cornual inseminations (n = 2127) were evaluated over a 3-yr period in Holstein and Jersey cattle. For cornual insemination one-half of each semen dose was deposited approximately 2.5 cm into each uterine horn. Conception rate was lower for cervical insemination (39.4%) than uterine body (48.1%) or cornual (49.3%) inseminations. Pregnancy site distribution was equal for both insemination techniques but cervical insemination resulted in 60% right horn pregnancies. Primary housing, service number, inseminator, lactation number, and sire affected conception rate. Older cows were least fertile (31.4%), second service conception rate was lowest (42.6%), and barn housed cattle had a 39.7% conception rate. Days open was affected by primary housing, service number, sire, site of semen placement, and twinning. Twinning increased days open by 10 d. Optimum time for insemination of lactating cows was between 6 and 12 h after the initial observation of estrus. From this study we conclude that shallow cornual insemination is as effective as uterine body insemination, and conception rate is optimized when estrus is positively assessed.

Animals↗