Biomedical subjects

G D Anderson

Publications and source records attributed to G D Anderson.

At least 19 recordsLinked to original sources

PubMed1992

Restricted heterogeneity in T-cell antigen receptor V beta gene usage in the lymph nodes and arthritic joints of mice.

We have used PCR to study the expression of T-cell antigen receptor beta RNA containing particular variable region (V) elements from transcripts directly in the cells isolated from joints and lymph nodes of B10.Q mice (H-2q) immunized with chicken type II collagen. Our data show that the T cells present in arthritic joints expressed only a few V beta transcripts--V beta 2, -6, -7, -8.2, -9, -10, and -15. V beta 6 and -8.2 were expressed predominantly (six out of seven animals) while others were expressed at a relatively low level in different animals. In lymph node cells, transcripts for V beta 6, -8.2, and -9 were detected in four out of seven animals. The data indicate that in collagen-induced arthritis there is a restrictive usage of TCR V beta elements and that V beta 6 and -8.2 are probably used preferentially.

Animals↗

PubMed1992

The effect of cesarean section on intraventricular hemorrhage in the preterm infant.

OBJECTIVE: The null hypothesis is that active labor is a more important factor with regard to both timing and progression of periventricular-intraventricular hemorrhage than is route of delivery. Infants delivered by cesarean section after entering the active phase of labor will behave in a manner similar to that of previously studied infants delivered vaginally as to when periventricular-intraventricular hemorrhage occurs and frequency of progression. STUDY DESIGN: The 106 infants of 85 women delivered by cesarean section were the subjects of this study. Forty-six infants were in the no-labor group, 33 in the latent-phase labor group, and 27 in the active-phase labor group. Head ultrasonographic examinations were performed at delivery, at 1, 6, 12, and 24 hours, and then daily for the first 7 days of life. Continuous variables were compared by one-way analysis of variance among those infants with no hemorrhage or with periventricular-intraventricular hemorrhage. Categoric variables were compared by chi 2 analysis and Fisher's exact test when appropriate. A p value of less than 0.05 was considered significant. RESULTS: There was no difference in the frequency of early hemorrhage (less than or equal to 1 hour of age), late hemorrhage (greater than 1 hour of age), or overall periventricular-intraventricular hemorrhage in the infants not in labor, in latent-phase labor, or in active-phase labor at the time of cesarean section. However, the frequency of grade 3 or 4 hemorrhage and the progression of hemorrhage were significantly higher in the infants whose mothers had an active phase of labor compared with infants whose mothers had no labor or did not progress beyond the latent phase. Infants who had early periventricular-intraventricular hemorrhage (less than or equal to 1 hour of age) also had a higher frequency of progression of hemorrhage. CONCLUSIONS: Cesarean section before the active phase of labor does not change the overall frequency of hemorrhage but results in a lower frequency of progression to grade 3 or 4 hemorrhage. We do not feel that these data support performing more cesarean sections for preterm delivery as a method of preventing progression of periventricular-intraventricular hemorrhage in the preterm infant.

Birth Weight↗

PubMed1992

The effect of valproate on the metabolism of phenobarbital in the rat.

Valproate has been shown to interact with all major antiepileptic drugs. The interaction with phenobarbital is the most clinically significant. The mechanism of the interaction was evaluated in the in vivo rat and in vitro liver perfusion system. Phenobarbital and parahydroxyphenobarbital (PbOH) were administered with and without valproate treatment. In vivo, after administration of PbOH, valproate caused a significant inhibition of both the renal clearance of unchanged PbOH (40%) and the formation clearance (ClF) of its glucuronide conjugate (44%). When coadministered with phenobarbital, valproate caused a significant decrease in the total plasma clearance of phenobarbital (95.4 +/- 29.0 to 65.8 +/- 20.2 ml/hr/kg), with no apparent effect on the phenobarbital renal clearance or the ClF of PbOH. Valproate did cause a significant inhibition (50%) of formation of a minor metabolite, metahydroxyphenobarbital. The largest effect of valproate appears to be on unknown pathways of phenobarbital elimination. In the isolated perfused rat liver, the ClF of PbOH and its glucuronide conjugate were determined. Valproate caused a small (10%) but significant decrease in the ClF of PbOH. As seen in vivo, the most significant effect of valproate was on the ClF of the PbOH glucuronide (66% decrease). In conclusion, inhibition of PbOH formation by valproate cannot account entirely for the increased plasma concentrations of phenobarbital that occur when valproate is added to therapy. A complete understanding of the mechanism will require a complete accounting of the phenobarbital dose in rat or in humans.

Animals↗

PubMed1992

Early and late intraventricular hemorrhage: the role of obstetric factors.

OBJECTIVE: To evaluate the influence of active phase labor and other obstetric factors on the development of periventricular-intraventricular hemorrhage in the neonate. METHODS: A total of 230 infants were studied. Antenatal enrollment was carried out when estimated fetal weight was 1750 g or less. Serial head ultrasound scans were performed to screen for periventricular-intraventricular hemorrhage, with the initial scan performed within minutes of birth. Scan findings and obstetric and neonatal variables collected prospectively at scheduled intervals were analyzed to determine the significant factors that predispose to intraventricular hemorrhage. RESULTS: In 47 infants (20%), intraventricular hemorrhage was detected within 1 hour of birth (early) and in another 49 (21%) at a later age (late). The overall incidence of hemorrhage was similar between vaginal and cesarean deliveries (41 and 44%, respectively). Early hemorrhage was more frequent in vaginal (28%) than cesarean deliveries (11%), whereas late hemorrhage was more frequent in cesarean deliveries. When the role of delivery mode and labor was analyzed by stepwise logistic regression, the odds ratios for development of early intraventricular hemorrhage increased in the following order: cesarean delivery with no labor, cesarean delivery with latent phase labor, vaginal delivery with forceps use, cesarean delivery with active phase labor, and vaginal delivery without forceps use. For late hemorrhage, the odds ratios increased in the following order: vaginal delivery with forceps, vaginal delivery without forceps, cesarean delivery with no labor, cesarean delivery with latent phase labor, and cesarean delivery with active phase labor. CONCLUSIONS: Active phase labor may predispose to early periventricular-intraventricular hemorrhage, but its influence may be attenuated by use of forceps or by abdominal delivery. The protective effect of forceps remains for late periventricular-intraventricular hemorrhage, but abdominal delivery does not seem to protect against late hemorrhage.

Cerebral Hemorrhage↗

PubMed1992

Vaginal birth after cesarean section at the University of Texas.

Vaginal delivery was successful in 76% of the 242 women who underwent a trial of labor after cesarean section in a prior pregnancy. Separation of the uterine scar occurred in four women (1.7%). Women whose prior cesarean section was for breech presentation had the highest rate of successful vaginal delivery (86%). The vaginal delivery rates were similar in women who delivered infants with birth weights > or = 4,000 g (73%) and < 4,000 g (76%). The use of epidural anesthesia and oxytocin may enhance the success of vaginal delivery in women undergoing a trial of labor following an earlier cesarean section.

Anesthesia, Epidural↗

PubMed1991

Role of Mls-1 locus and clonal deletion of T cells in susceptibility to collagen-induced arthritis in mice.

The role of T cell-mediated and humoral immunity to type II collagen has been well documented in collagen-induced arthritis (CIA). Previous work from our laboratory has indicated that genomic deletions of TCR V beta genes may play a role in CIA resistance in mice. This indicated a selectivity of TCR usage by autoreactive T cells in CIA in mice. Certain strains of mice, although having a normal genomic V beta TCR repertoire, can show clonal deletion of peripheral T cells that bear specific V beta gene products in their TCR. These clonally deleted T cells are reactive with self-Ag such as minor lymphocyte stimulation (Mls) Ag. An Mls-congenic strain, BALB.D2.Mlsa, which differs only at the Mls-1 a locus from BALB/c (Mls-1b), was used to examine the effect of clonal deletion of Mls-1a-reactive T cells in CIA. These two strains were crossed to three CIA-susceptible strains, B10.RIII (H-2r, Mls-1b), DBA/1 (H-2q, Mls-1a), and B10.Q (H-2q, Mls-1b), and the crosses were injected with type II collagen. A significantly decreased incidence of arthritis was observed in the (BALB.D2.Mlsa x B10.Q)F1 hybrids, compared with (BALB/c x B10.Q)F1 hybrids, upon immunization with chick type II collagen. The BALB.D2.Mlsa cross mice also had significantly lower levels of antimouse collagen antibodies. Flow cytometric analysis confirmed the clonal deletion of Mls-1a-reactive V beta 8.1, V beta 6, V beta 7, and V beta 9 subsets in the (BALB.D2.Mlsa x B10.Q)F1 hybrids. The study of H-2q/d mice in (BALB.D2.Mlsa x B10.Q) x B10.Q back-crosses demonstrated a significant correlation between CIA resistance and Mls-1a locus. On the other hand, B10.RIII crosses showed only a modest decrease in CIA incidence in the presence of Mls-1a. As expected, all the DBA/1 crosses had an equal incidence of CIA, which was somewhat less than that seen in DBA/1 mice themselves. These studies point out that the Mls-1a locus could play a role in decreasing CIA incidence by clonal deletion of T cells bearing specific V beta TCR, which may be involved in the pathogenesis of CIA. The influence of the clonal deletion of T cells on CIA, and hence the usage of specific V beta TCR by autoreactive anti-type II collagen T cells, however, depends not only on the source of the type II collagen and the MHC class II molecules involved but also on other background genes in mice.

Animals↗

PubMed1991

Thymic deletion of V beta 11+, V beta 5+ T cells in H-2E negative, HLA-DQ beta+ single transgenic mice.

DQw6b transgenic mice have been generated by microinjecting a linearized cosmid clone containing 34-kb DQb genomic DNA, isolated from HLA-homozygous B cell line AKIBA (DR2, Dw12, DQw6), into embryos of (CBA x B10.M)F2 or (SWR x SJL)F2. Among 85 mice screened, eight mice were transgene-positive. The transgene in seven of eight founders was germline-transmitted. FACS analysis and immunohistochemical studies with DQ beta-specific mAb demonstrated that DQ beta molecules in association with mouse A alpha f molecules are expressed on peripheral mononuclear cells, spleen cells, and in thymic medulla. More interestingly, V beta 11-, V beta 5.1-, and V beta 5.2-bearing T cells, but not V beta 8.2-bearing T cells, were clonally deleted in the H-2E-negative but DQ beta+ progeny of two selected founders (260-23 and 258-10). The deletion was found to take place intrathymically during the transition stage from immature to mature thymocyte development. We postulate that although human DQ genes are more homologous to mouse H-2A genes, A alpha f/DQ beta hybrid molecules may possess the same self-peptide- (or superantigen)-presenting epitope as E alpha/E beta molecules critical for deletion of V beta 11-, V beta 5.1-, and V beta 5.2-bearing T cells in thymus. Our results also confirm the previous findings that accessory molecules on thymocytes such as CD4 may be involved in thymic selection, and further suggest that an interaction of mousE CD4 and mouse A alpha chain is required for the clonal deletion.

Animals↗

PubMed1991

Drug abuse and other risk factors for physical abuse in pregnancy among white non-Hispanic, black, and Hispanic women.

We investigated prevalence and risk factors associated with physical abuse among a tricultural population of 501 pregnant women who attended a public prenatal clinic. Twenty percent (98/501) reported being physically abused; 29% (28/98) stated that abuse occurred during pregnancy. More white non-Hispanic women reported previous abuse than did black or Hispanic women. Battered women more frequently were divorced or separated, were of greater parity, smoked, used alcohol, or admitted to illicit drug use than did women who were not battered. An increased risk of previous physical abuse was observed among white non-Hispanic and black women who used alcohol (odds ratios = 3.0 and 6.0) or drugs (odds ratios = 2.1 and 3.7) but not among Hispanic women. Odds ratios of 4.7 for cocaine use among white non-Hispanic women, 4.7 for marijuana use among black women, and 5.8 for tobacco use among Hispanic women were observed. This is the first study to report the effects of race on the association between physical abuse of pregnant women and substance use.

Black or African American↗

PubMed1991

Human HLA-DQ beta chain presents minor lymphocyte stimulating locus gene products and clonally deletes TCR V beta 6+, V beta 8.1+ T cells in single transgenic mice.

Minor lymphocyte stimulating locus (Mls) gene products in association with mouse major histocompatibility complex (MHC) class II molecules are known to determine the repertoire of T-cell receptor (TCR) in mature T cells. In order to test whether human class II molecules can present mouse Mls, HLA-DQ beta transgenic mice were generated. The expression and function of the DQ beta transgene were studied in the progeny of one selected founder which was H-2f and H-2E negative. In these mice, DQ beta molecules pairing with mouse A alpha chain and invariant chain are expressed on the cell surface in a tissue-specific manner. When the DQ beta gene was bred into the Mls-1a strain DBA/1 (H-2q), T cells bearing V beta 6 and V beta 8.1 TCR were clonally deleted in the thymus of DQ beta+ transgenics but not in DQ beta-negative full sibs. Thus, the data presented here clearly demonstrate that the human MHC DQ beta chain can present Mls in the clonal deletion of T cells. Our results also suggest the requirement for an interaction between CD4 and class II molecules (alpha chain) for clonal deletion of T cells to occur.

Animals↗

PubMed1990

A comparison of no medication versus methyldopa or labetalol in chronic hypertension during pregnancy.

Three hundred women with mild chronic hypertension at 6 to 13 weeks' gestation were randomly allocated to receive either methyldopa or labetalol or be in the control group. Thirty-seven women (12%) were excluded for various reasons. Of the remaining 263 patients, 90 received no drug, 87 received methyldopa, and 86 received labetalol. All 263 were followed throughout pregnancy with serial renal function tests and serial assessment of fetal status. There were no differences among the three groups in mean systolic or diastolic blood pressures, mean gestational age, or initial laboratory findings at time of entry. Patients treated with medications had significantly lower (p less than 0.0001) systolic and diastolic blood pressures throughout gestation compared with the no-medication group. Among the control group there was a spontaneously significant lowering (p less than 0.0001) of both systolic and diastolic blood pressures at 14 to 26 weeks' gestation. However, there were no differences among the three groups regarding the incidences of either superimposed preeclampsia (15.6%, 18.4%, and 16.3%, respectively), abruptio placentae (2.2%, 1.1%, and 2.3%, respectively), or preterm delivery (10%, 12.5%, and 11.6%, respectively). In addition, there were no differences among the groups regarding gestational age at delivery, birth weight, incidence of fetal growth retardation, or neonatal head circumference. There was one midtrimester loss in the methyldopa group and one stillbirth in each of the other groups. We conclude that treatment of maternal blood pressure in mild chronic hypertension during pregnancy did not improve perinatal outcome.

Adult↗

PubMed1990

Frequent handling in the neonatal intensive care unit and intraventricular hemorrhage.

The association between periventricular-intraventricular hemorrhage (PV-IVH) and frequent handling resulting from various neonatal intensive care procedures and routine interventions was evaluated in a prospective clinical study. Inborn premature babies with birth weight less than or equal to 1500 gm (n = 156) who did not have PV-IVH or who had grade 1 PV-IVH at less than or equal to 1 hour were randomly assigned to the reduced manipulation protocol (n = 62) or to standard care (n = 94). A bedside microcomputer-based data acquisition system was used to monitor the duration of rest or the number of interventions per day. Infants assigned to receive reduced manipulation spent a significantly higher percentage of time each day at rest than did those who received standard manipulation (p less than 0.006). However, the incidence of grades 2 to 4 PV-IVH did not differ significantly (30% in the study vs 37% in the standard manipulation group). When we analyzed the effect of manipulation in relation to risk of PV-IVH, while taking into account other perinatal variables, standard manipulation was not associated with increased risk of grades 2 to 4 PV-IVH. However, low birth weight, maternal smoking, general anesthesia, early grade 1 PV-IVH, low hematocrit, lowest arterial oxygen pressure within the first 6 hours of life, and large base deficit at 6 hours of age all increased the relative risk of grades 2 to 4 PV-IVH.

Cerebral Hemorrhage↗

PubMed1990

Effects of polytherapy with phenytoin, carbamazepine, and stiripentol on formation of 4-ene-valproate, a hepatotoxic metabolite of valproic acid.

The incidence of valproic acid hepatotoxicity has been reported to increase in patients who are receiving polytherapy. A minor valproic acid metabolite, 2-propyl-4-pentenoic acid (4-ene-VPA), formed by a cytochrome P450-mediated reaction, has been shown to be a potent inducer of microvesicular steatosis in rats. This study tested the hypothesis that formation of 4-ene-VPA would be increased in patients taking valproic acid with carbamazepine or with phenytoin but decreased with coadministration of an inhibitor of cytochrome P450 (the antiepileptic drug stiripentol in 300 to 1200 mg daily doses) in healthy subjects. Blood and urine samples in the studies were collected during a dosing interval at steady state. Valproic acid was assayed in plasma by capillary gas chromatography; valproic acid and 15 metabolites were measured in urine by gas chromatography/mass spectrometry. The formation clearance (CLf) of 4-ene-VPA was increased twofold in the valproic acid-carbamazepine and valproic acid-phenytoin groups. In the valproic acid/stiripentol studies, the CLf of 4-ene-VPA decreased by 32% in the 1200 mg/day stiripentol study. Similar findings were obtained at 600 and 300 mg/day stiripentol. These findings provide evidence supporting a role for cytochrome P450 in the formation of the hepatotoxic metabolite, 4-ene-VPA, in humans. The increased formation of 4-ene-VPA associated with carbamazepine and phenytoin is striking in relation to the epidemiologic finding of increased incidence of valproic acid-related hepatotoxicity during polytherapy with P450 inducers.

Adult↗

PubMed1990

An investigation into the effects of oral iron supplementation on in vivo Hemoccult stool testing.

This prospective, randomized, double-blind, crossover study examined the effects of oral iron ingestion on fecal occult blood testing. One hundred healthy and asymptomatic volunteers collected stool samples after 2-wk courses of both oral iron (either ferrous sulfate or ferrous gluconate) and placebo, while following strict medicinal, dietary, and collection instructions. Each sample was tested by both the Hemoccult II and Hemoccult Sensa methods. Of the participants who completed this study (n = 78), there were no positive results for occult blood after iron ingestion when tested by either method. Only one participant displayed a positive result while taking the placebo, with this specimen considered contaminated by unexpected menses. From these findings, it can be concluded that oral iron supplementation does not cause false-positive results when the Hemoccult II or Hemoccult Sensa method is used for fecal occult blood testing.

Administration, Oral↗

PubMed1989

MHC class II A alpha and E alpha molecules determine the clonal deletion of V beta 6+ T cells. Studies with recombinant and transgenic mice.

Interactions between MHC class II genes and minor lymphocyte stimulating (Mls) associated products are responsible for clonally deleting self-reactive T cells in mice. Here we demonstrate the role of the intact I-A and I-E molecules as well as the individual A alpha and E alpha chains in the deletion of cells bearing the V beta 6 TCR. DBA/1 (H-2q, Mls-1a) mice were crossed with various inbred congenic, recombinant, and transgenic strains and the F1's were screened for V beta 6 expression. All I-E+ strains were fully permissive in deleting V beta 6+ T cells. I-E- strains expressing I-A b,f,s,k,p permitted only partial deletion, while I-Aq strains showed no deletion. Recombinant I-Aq and I-Af strains which expressed E kappa alpha chain in the absence of E beta chain showed a decrease in V beta 6+ T cells as compared to their H-2q and H-2f counterparts. Furthermore, transgenic mice expressing E kappa alpha Aq beta gene in an H-2q haplotype (E kappa alpha Aq beta?) gave similar results to that of the recombinants in deleting V beta 6 T-cells. The role of the 1-A molecule was also shown by the partial deletion of V beta 6+ T cells in H-2q mice expressing transgenic I-Ak molecules. These results demonstrate that the E alpha chain is important in the deletion of V beta 6 T-cells in Mls-1a mice. The role of A alpha chain is also implied by the permissiveness of E kappa alpha Aq beta but not Aq alpha Aq beta molecules in the deletion of V beta 6+ T cells.

Animals↗

PubMed1989

In vivo expression and function of hybrid Ia dimers (E alpha A beta) in recombinant and transgenic mice.

We have found cell surface expression of an E alpha molecule in recombinant and transgenic mouse strains lacking an E beta molecule. Flow cytometry has shown low level expression of E alpha in B10.RQB3 (I-AqEk alpha) and B10.RFB2 (I-AfEk alpha) mice. We have also found that B10.Q (H-2q) mice can express the Ek alpha transgene. Since these strains do not have functional E beta chains, we propose that the E alpha A beta hybrid dimers are formed in low numbers and can be picked up by FACS analysis. So far we have not been able to identify these hybrid molecules by cytotoxicity or immunoprecipitation. The E alpha/A beta molecule can function in vivo during thymic selection in the clonal deletion of two V beta TCR subsets, V beta 11 and V beta 6, which have been shown to interact with the intact I-E molecule.

Animals↗

PubMed1989

RIII S/J (H-2r). An inbred mouse strain with a massive deletion of T cell receptor V beta genes.

We have identified an inbred strain of mouse, RIII S/J (H-2r), that has the largest known deletion of the TCR V beta genes by screening with mAb and TCR V beta specific probes. Upon screening of PBL with mAb F23.1, which is specific for V beta 8 TCR, RIII S/J was found to be negative. On further screening with mAb KJ 23a, which is specific for V beta 17a TCR, RIII S/J was completely negative. We next tested RIII S/J with mAb 44-22-1, which is specific for V beta 6 TCR, and found it also to be negative. The (B10 X RIII)F1 mice showed a 50% expression of V beta 6 gene, indicating a genomic rather than a clonal deletion. mAb KJ25, detecting V beta 3, was positive in RIII S/J, denoting the downstream boundary for the deletion. Southern blot analysis of liver DNA using TCR V beta-specific probes confirmed the deletion of V beta 8 gene subfamily and V beta 5 gene subfamily, along with V beta 9, V beta 11, V beta 12, and V beta 13 genes similar to the known TCR V beta deletion mutants (SWR, SJL, C57L, and C57Br). In addition, RIII S/J is missing V beta 6, V beta 15, and V beta 17 genes. Our mapping of the deletion indicates that RIII S/J has lost approximately 130 kb of V beta chromosome and with it 13 V beta genes out of the known 21 V beta genes of the TCR. The deletion is marked by the presence of V beta 10 gene upstream and V beta 3 gene downstream.

Animals↗

PubMed1989

Influence of complement C5 and V beta T cell receptor mutations on susceptibility to collagen-induced arthritis in mice.

SWR/J mice are resistant to collagen-induced arthritis (CIA) despite having a susceptible H-2q haplotype. We have earlier demonstrated the possible role of the V beta TCR mutation of SWR in the resistance to CIA. To investigate the influence of the C5 deficiency of SWR in this resistance, crosses were made between SWR and A/J (C5 deficient, TCRwild, H-2a), and between SWR and C3H.A (C5 sufficient, TCRwild, H-2a). Upon immunization with bovine type II collagen in adjuvant, there was a similar incidence and severity of arthritis in H-2q-bearing mice in the back-crosses A x (SWR x A) ad C3H.A x (SWR x C3H.A). The absence of hemolytic complement was confirmed in the arthritic A x (SWR x A) back-cross mice by standard SRBC hemolytic assays. In addition C57L (H-2b) mice, which were C5 sufficient but had a V beta TCR deletion mutation similar to SWR, could not complement for CIA susceptibility in H-2q-bearing C57L x (SWR x C57L) back-crosses and in (C57L x SWR)F2 hybrids. These studies show that complement C5 does not play a significant role in CIA susceptibility, and further implicate the V beta TCR mutation in the resistance to CIA in SWR mice.

Animals↗

PubMed1989

Lack of evidence of a vasodepressor role for relaxin in spontaneously hypertensive and normotensive pregnant rats.

To test the possibility that the ovarian polypeptide hormone relaxin mediates the vasodepressor effect of pregnancy, we measured changes in blood pressure in three groups of spontaneously hypertensive and Wistar-Kyoto normotensive rats: (1) pregnant, bilaterally oophorectomized rats on postmating day 13, (2) pregnant, sham-oophorectomized rats on postmating day 13, and (3) nonpregnant, sham-oophorectomized rats after 13 days. The day before parturition we also measured the pressor responsiveness to angiotensin II and norepinephrine. Systolic blood pressure fell significantly during the last week of gestation in both strains, reaching normotensive levels in the hypertensive rats by term. The pressor responsiveness to angiotensin II, but not norepinephrine, of the pregnant rats was reduced compared with that of the nonpregnant rats in both strains. Oophorectomy did not prevent the fall in blood pressure or the decrease in vascular reactivity to angiotensin II. Therefore, although ovarian relaxin secretion increases during pregnancy, it apparently does not decrease vascular sensitivity to angiotensin II or cause vasodilation.

Angiotensin II↗