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H Wallace

Publications and source records attributed to H Wallace.

At least 37 records · Page 2Linked to original sources
PubMed1997

Risk status at discharge and cause of death for postneonatal infant deaths: a total population study.

OBJECTIVES: To obtain population-based, clinical information regarding potentially modifiable factors contributing to death during the postneonatal period (28 to 364 days), we examined all postneonatal infant deaths in four areas of the United States to determine: (1) the cause of death from clinical and autopsy data rather than vital statistics, (2) whether death occurred during initial hospitalization or after discharge, and (3) the portion of postneonatal mortality attributable to infants who left the hospital with identified high-risk medical conditions. DESIGN AND SETTING: Retrospective medical record review of all postneonatal infant deaths with birth weights greater than 500 g (total N = 386) born to mothers residing in: (1) the city of Boston (1984 and 1985, N = 55), (2) the city of St Louis and contiguous areas (1985 and 1986, N = 123), (3) San Diego County (1985, N = 112), and (4) the state of Maine (1984 and 1985, N = 96). Deaths were identified using linked birth and death vital statistics, and medical record audits of infants' and mothers' charts were performed. Causes of death were obtained from medical record review in conjunction with autopsy if performed (72%, N = 278), medical record alone (17%, N = 67), or vital statistics if no other source was available (11%, N = 41). The medical conditions at the time of discharge for each infant were reviewed and, if judged to confer an increased risk of morbidity or mortality, were classified as high risk. RESULTS: The causes of death were sudden infant death syndrome (47%, N = 181), congenital conditions (20%, N = 77), prematurity-related conditions (11%, N = 43), infections (9%, N = 34), external causes (including injuries, drownings, ingestions, and burns) (7%, N = 25), and other (6%, N = 23). In 24% of congenital and 25% to 44% of prematurity-related deaths, infection was the acute or associated cause of death. Infants born to black mothers were more likely than those born to white mothers to die during the postneonatal period of all major causes of death (7.3 per 1000 vs 3.0 per 1000). Overall, 18% (N = 68) of deaths occurred to infants who never left the hospital; 79% (N = 305) of the infants were discharged before death; and discharge status was unknown in 3% (N = 13). Eighty-one percent of all infants with prematurity-related postneonatal deaths were never discharged, and of the total infants who were initially discharged, only 1% (N = 4) subsequently died of prematurity-related causes. Of all postneonatal deaths, only 16% (N = 62) left the hospital with identified high-risk medical conditions. CONCLUSIONS: These findings suggest that the etiology of postneonatal mortality is heterogeneous, with significant complexity in attributing specific causes of death and making designations of "preventability." The vast majority of infants who died of prematurity-related postneonatal causes never left the hospital, and only a small percentage of all infants that left the hospital before death were identified as being at high medical risk. Therefore, strategies for further decreasing postneonatal mortality must link high-risk follow-up programs to more comprehensive strategies that address risk throughout pregnancy and early childhood.

Cause of Death↗
PubMed1996

Ganciclovir-induced ablation non-proliferating thyrocytes expressing herpesvirus thymidine kinase occurs by p53-independent apoptosis.

In adult mice of the transgenic strain TG66.19, in which expression of herpes simplex type 1 virus thymidine kinase (HSVI-TK) is driven in thyrocytes from the thyroglobulin promoter, the drug Ganciclovir causes the death (ablation) of thyrocytes. Ablation occurred in the absence of thyrocyte proliferation or nuclear DNA synthesis, but was accompanied by transient expression of proliferating cell nuclear antigen and the dying thyrocytes exhibited the ultrastructural features of apoptosis. Control experiments show that the apoptosis is a result of the production of Ganciclovir phosphates in thyrocytes that express HSV1-TK. However, cell death was not dependent upon the presence of a functional copy of the oncosuppressor gene p53. We conclude that the apoptosis is probably not mediated by induction of DNA damage and occurs via a pathway that is independent of p53. The fact that Ganciclovir phosphate can kill cells by a p53-independent apoptotic pathway is encouraging in relation to tumour ablation by methods based on transfection with HSV1-tk genes and administration of Ganciclovir.

Animals↗
PubMed1996

Selective ablation of differentiated cells permits isolation of embryonic stem cell lines from murine embryos with a non-permissive genetic background.

Embryonic stem (ES) cells enable the engineering of precise modifications to the mouse genome by gene targeting. Although there are reports of cultured cell contributions to chimaeras in golden hamster, rat and pig, definitive ES cell lines which contribute to the germline have not been demonstrated in any species but mouse. Among mouse strains, genetic background strongly affects the efficiency of ES isolation, and almost all ES lines in use are derived from strain 129 (refs 1,4,5) or, less commonly, C57BL/6 (refs 6-8). The CBA strain is refractory to ES isolation and there are no published reports of CBA-derived ES lines. Hence, CBA mice may provide a convenient model of ES isolation in other species. In ES derivation it is critical that the primary explant be cultured for a sufficient time to allow multiplication of ES cell progenitors, yet without allowing extensive differentiation. Thus, differences in ES derivation between mouse strains may reflect differences in the control of ES progenitor cells by other lineages within the embryo. Here we describe a strategy to continuously remove differentiated cells by drug selection, which generates germline competent ES lines from genotypes that are non-permissive in the absence of selection.

Animals↗
PubMed1996

Case report: immunoglobulin M-mediated, temperature-dependent neutrophil agglutination as a cause of pseudoneutropenia.

The authors report the case of a 77-year-old man in whom intermittent neutropenia developed during a prolonged hospitalization. Laboratory records revealed wide variations in the patient's routine leukocyte counts. Examination of the peripheral smear revealed clumps of 2-3 polymorphonuclear leukocytes throughout the slide and large aggregates (> 50 cells) along the smear edges. Neutrophil clumping also was observed in blood anticoagulated with citrate or heparin. Replacement of patient plasma with saline prevented agglutination. Addition of patient plasma or serum to normal cells induced neutrophil agglutination. Holding the patients blood at 37 degrees C prevented agglutination, which occurred spontaneously and more exuberantly as the temperature was reduced to 22 degrees C. Flow cytometry revealed immunoglobulin M on neutrophil surfaces. Spontaneous agglutination resolved 6 months after resection of the patient's subsequently diagnosed colon cancer. This is the first report of immunoglobulin M-induced neutrophil clumping occurring in the setting of malignancy, and the first reported immunoglobulin M not to require ethylenediaminetetraacetic acid as a cofactor for agglutination.

Adult↗
PubMed1995

Different transmission rates of herpesvirus thymidine kinase reporter transgenes from founder male parents and male parents of subsequent generations.

Previously we demonstrated that lines of transgenic mice carrying the herpes simplex type 1 virus thymidine kinase (HSV1-tk) reporter gene are male-sterile. Ectopic transcription of the HSV1-tk reporter in the testis was initiated downstream of the normal translation initiation codon and truncated proteins consistent with translational initiation at the second and third ATG codons were synthesized. Here we describe the effects on fertility 1) of converting the second and third ATG codons of the HSV1-tk reporter to CTG codons and 2) of utilizing the HSV type 2 thymidine kinase (HSV2-tk) reporter gene, in which the second ATG codon is located downstream of the ATP-binding pocket of the enzyme. Both reporters were coupled to the bovine thyroglobulin promoter (bTG-tk1 alpha and bTG-tk2 transgenes). The level of ectopic expression of these transgenes in the testis, relative to expression in the thyroid, was one to two orders of magnitude less than that of bTG-tk1. Sixty percent of male founders carrying the bTG-tk1 alpha and bTG-tk2 transgenes were fertile but did not transmit the transgene. In contrast, most males from subsequent generations were fertile and transmitted the transgenes at the expected frequency. This difference between founder males and male descendants is also observed with certain constructs in which the HSV1-tk reporter is coupled to other promoters. We attribute the effect to mosaicism among male founders, leading to competition between transgenic and nontransgenic spermatozoa and/or spermatogenic precursor cells and resulting in a lack of fertilization by transgenic sperm that would successfully fertilize eggs in the absence of competition.

Animals↗
PubMed1995

Effects of perinatal thyroid hormone deprivation on the growth and behaviour of newborn mice.

Experiments were designed to distinguish between neonatal effects due to maternal thyroxine (T4) deprivation and those due to autonomous (fetus/pup) T4 deprivation, employing mice heterozygous for the bTG-tk transgene TG66,19 which specifically directs high-level expression of herpes virus type I thymidine kinase to the thyrocytes. Heterozygous TG66.19 females were either untreated or Ganciclovir was administered to destroy their thyrocytes and so render them T4-deficient. When mated to normal males these heterozygous females are expected to produce on average 50% normal and 50% heterozygous transgenic conceptuses. Ganciclovir was administered to the dams (both untreated and Ganciclovir-pretreated) during days 14-18 of gestation. At optimum levels of in utero Ganciclovir administration the non-transgenic pups showed no discernible effect while the transgenic pups were rendered athyrocytic and completely T4-deficient. The dams pretreated with Ganciclovir are hypothyroid throughout gestation, while the dams to which Ganciclovir was administered for the first time during gestation are not expected to become hypothyroid until about the time of parturition. In this way four sets of pups were generated for purposes of comparison: hypothyroid (transgenic) and euthyroid (non-transgenic) pups born to euthyroid dams and hypothyroid and euthyroid pups born to hypothyroid (Ganciclovir-pretreated) dams. Normal growth during days 1-10 after birth was dominated by the T4 status of the dam during gestation. Growth during days 11-21 and the correct timing of eye opening and ear elevation were dominated by the autonomous T4 status of the fetus/pup. The timely development of the surface-righting reflex (relative to weight gain) was shown to require both maternal and fetus/pup T4. The development of the cliff-avoidance reflex was independent of the T4 status of both pup and dam and of pup weight. The size of the pups at birth depended primarily on a normal T4 status in the dam but surprisingly T4 deficiency in fetuses/pups partly compensated for maternal T4 deficiency. The results presented here clearly demonstrate the utility of the HSV-tk-transgene-Ganciclovir-administration protocol in studying the interplay of maternal and fetal T4 deprivation in rodents.

Animals↗
PubMed1994

Autoantibodies to myeloperoxidase in idiopathic and drug-induced systemic lupus erythematosus and vasculitis.

Circulating antibodies to myeloperoxidase (MPO) have been described in a variety of vasculitic syndromes, drug-induced SLE and drug-induced nephritis. We have examined the autoantibody profile in acute sera from patients with antineutrophil cytoplasmic antibody-positive vasculitis (n = 8), drug-induced nephritis (n = 4), drug-induced lupus (n = 7), SLE (n = 27) and nephritis-associated with SLE (n = 17). Significant binding to purified MPO in ELISA was given by all sera from patients with vasculitis and drug-induced nephritis but ANA sought by indirect immunofluorescence on HEp-2 cells were not detected. Both anti-MPO and ANA were found in sera from patients with drug-induced lupus. Sera from patients with SLE or SLE nephritis did not contain high titres of anti-MPO antibodies but invariably contained ANA. Anti-MPO antibodies of both IgG and IgM classes were present in all sera from patients with drug-induced disease. Although the number of samples tested was small, sera from patients with drug-induced nephritis showed significantly greater median % binding of IgM to MPO compared with drug-induced SLE. Binding to MPO by IgG in these sera was not significantly different. These findings suggest that the mechanism of interaction between hydralazine and the immune system in the two drug-induced autoimmune diseases studied may contribute to their distinct clinical features.

Adolescent↗
PubMed1994

Consequences of thyroid hormone deficiency induced by the specific ablation of thyroid follicle cells in adult transgenic mice.

The herpes simplex type 1 virus thymidine kinase (HSV1-TK) reporter gene was coupled to a bovine thyroglobulin promoter (TG-tk construct). Within the thyroid glands of transgenic mice expression was confined to thyroid follicle cells. Infusion of Ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl]guanine) to 8 to 12 week transgenic females led to the complete loss of thyroid HSV1-TK activity (at 3 to 4 days) and thyroid follicles (between 7 and 14 days). During the first 5 days of treatment a single reciprocal oscillation in circulating thyroxine (T4) and TSH levels occurred. By 14 days the circulating tri-iodothyronine (T3) and T4 levels of all treated animals were below the detection limits of the assays, while TSH levels were elevated ten-fold and continued to increase thereafter. During 14 days of treatment the thyroids regressed, protein content fell by 80-90% and the C cells, normally dispersed within the central region of each gland, came together in aggregates. Pituitary GH levels in females rose and fell back to normal within 14 days and between 14 and 28 days fell to a level comparable with that of GH-deficient lit/lit mice. The levels of hepatic GH receptor mRNA and the predominant 6.6 kb T3 receptor mRNA were unaffected by thyrocyte ablation. Thyrocyte ablation had no effect on the level of prolactin (Prl) receptor mRNA in females, but increased Prl receptor mRNA levels in males and eliminated group 1 major urinary protein (MUP).mRNA in females. T4 replacement reversed the effects of thyrocyte ablation on MUP mRNA in females and on Prl receptor mRNA in males.2+ Despite the many physiological changes induced by thyrocyte ablation, ablated mice have been maintained for up to 1 year without thyroid hormone supplementation. T4-deficient females were normally fertile and carried pups to term. Although transgenic males expressed HSV1-TK ectopically in spermatids and spermatozoa at levels similar to thyrocyte levels, a rate of Ganciclovir infusion which successfully ablated the thyrocytes did not affect the testis. As an alternative to infusion by minipump, thyrocyte ablation could be achieved by 6 twice-daily injections of Ganciclovir, at a level of 112 micrograms Ganciclovir/g body weight per day, and fetuses in utero could be thyrocyte ablated by administering 50 or 15 micrograms/g body weight per day to pregnant females between days 14 and 18 of gestation. These data demonstrate the potential value of transgenic thyrocyte ablation in the study of the effects of thyroid hormone deprivation.

Animals↗
PubMed1994

The effect of nonsteroidal agents (NSAIDs) on the pharmacokinetics and pharmacodynamics of metolazone.

NSAIDs attenuate the natriuretic response to loop diuretics. Their effect on the action of distal tubular diuretics is poorly explored. Accordingly, the pharmacokinetics and pharmacodynamics of metolazone [M], a distal tubular diuretic, with and without indomethacin [M+I] or sulindac [M+S] were examined in six healthy volunteers. Urine samples were obtained over 36 hours post-metolazone dosing for the determination of sodium, potassium and metolazone concentration. Though cumulative M excretion 750 +/- 247 [mucg/36 h] [M]; 749 +/- 239 [M+I]; 848 +/- 443 [M+S] was comparable between treatment groups, total sodium [Na+] excretion was significantly depressed in the presence of S or I, 685 +/- 114 [mEq/36 h] [M]; 454 +/- 90 [M+I] (p < or = 0.05); 553 +/- 123 [M+S] (p < or = 0.05). Peak Na+ excretion [muEq/min] was significantly decreased by I only and time to peak Na+ excretion did not differ amongst treatment groups. Total potassium [K+] excretion 160 +/- 39 [mEq/36 h] [M]; 111 +/- 53 [M+I] (p < or = 0.05); 135 +/- 31 [M+S] significantly decreased with I. This phenomenon was most evident between 12 and 36 hours. The administration of I or S with M significantly blunted sodium excretion on a purely pharmacodynamic basis while the decline in urinary potassium excretion upon addition of I to M related probably to an attenuation of braking phenomenon induced kaliuresis. These findings likely reflect NSAID-induced sodium reabsorption at loci prior to the site of action of metolazone.

Administration, Oral↗
PubMed1992

Sexual dimorphism and growth hormone regulation of a hybrid gene in transgenic mice.

The sexually dimorphic expression of the urinary protein genes of mice (Mup genes) in the liver is mediated by the different male and female temporal patterns of circulating GH. Normal females were induced to male levels when GH was administered by injection to mimic the male GH pattern, showing that expression at the male level does not require a male sex steroid status in addition to intermittent GH. Two Mup-alpha 2u-globulin hybrid transgenes with different Mup gene promoters showed sexually dimorphic expression, and their expression in females increased to male levels upon testosterone treatment. GH-deficient (lit/lit) mice did not express these transgenes, and GH-deficient females did not respond to testosterone treatment, showing that GH was required for induction. Both normal and GH-deficient females were induced to male levels when GH was administered by injection. This is the first report of a transgene responsive to GH. A transgene consisting of a Mup promoter fused to a Herpes simplex virus thymidine kinase reporter sequence also showed sexual dimorphism, although to a lesser degree. It was expressed at the same level in normal females and GH-deficient mice of both sexes and was induced when GH-deficient mice were treated with GH. We propose that this transgene has a basal constitutive expression, possibly due to the absence of any rodent DNA downstream of the promoter. Since expression of the transgene was significantly induced by GH, the GH response is due at least in part to sequences in the promoter region.

Alpha-Globulins↗
PubMed1991

The herpes simplex virus type 1 thymidine kinase is expressed in the testes of transgenic mice under the control of a cryptic promoter.

We reported previously that the herpes simplex virus type 1 (HSV-1) thymidine kinase reporter gene (tk) was expressed in the testes of transgenic mice when coupled to the promoter of a liver-specific mouse major urinary protein (MUP) gene. Here we show that HSV-1 tk is also expressed in the testis when coupled to a MUP pseudogene promoter, to a truncated MUP promoter that is not active in the liver, and to the promoter of the bovine thyroglobulin gene. Furthermore, HSV-1 tk itself was expressed in the testis, although its normal expression had been disabled by removing an upstream regulator of transcription. In every case, the same multiple transcripts were observed, with their 5' ends located downstream of the normal HSV-1 tk translation initiation codon. We conclude that the transcription of HSV-1 tk in the testis is directed by a cryptic TATA box-independent promoter located in the coding region of the gene. The longest HSV-1 thymidine kinase (TK) polypeptides synthesized in the testis were shorter than full-length TK and probably result from translational initiation at Met46 and Met60, the second and third ATG codons of the tk reading frame. Male mice of most transgenic lines were sterile, and the severity of the lesion in spermatogenesis was directly related to the level of TK expression. In the most highly expressing lines, sperm counts were low and morphologically defective sperm were common. In other sterile lines, TK was expressed at a lower level and sperm counts were normal but sperm motility was greatly reduced. Lines with the lowest levels of HSV-1 TK expression were fertile. HSV-1 TK was expressed in germ line cells, mainly in the haploid spermatids. However, low-level HSV-1 TK activity was found in the testis before the first germ cells entered meiosis, showing that if expression is confined to the germ cells, it also occurs in spermatogonia.

Animals↗
PubMed1991

Specific ablation of thyroid follicle cells in adult transgenic mice.

The coding region of the herpes simplex type 1 virus thymidine kinase gene was coupled to the promoter of the bovine thyroglobulin gene and introduced into the genome of mice. The viral thymidine kinase (HSV1-TK) was expressed mainly in the thyroid glands and testis. Upon treatment of transgenic females with the antiherpetic agent Ganciclovir the thyroid regressed, while the parathyroid gland was unaffected. The number of thyroid follicle cells was greatly reduced after 3 days, and they were completely absent after 7 days of treatment. After 14 days, the levels of circulating T4 and T3 were below the limits of detection, total soluble protein recovered from the thyroid and parathyroid glands together was 10% of the control value, and the level of thyroid HSV1-TK was more than 100-fold lower than that in transgenic controls. Levels of circulating PTH and calcitonin remained normal. At the time of treatment the mice were adults. Thus, the thyroid follicle cells were selectively ablated after normal development with a functional thyroid gland. When treatment with Ganciclovir was terminated after 14 days, no circulating T4 or T3 or other indications of thyroid regeneration were detected for a subsequent period of 90 days. During this time the mice gained weight more slowly than controls, at a rate consistent with the suppression of GH synthesis by thyroid deficiency. The production of mouse major urinary protein (MUP) ceased in the treated mice and was completely restored by the administration of T4. MUP production was not restored by GH, demonstrating that the expression of the Mup genes requires T4 in addition to GH.

Animals↗
PubMed1990

Islands of acetylated histone H4 in polytene chromosomes and their relationship to chromatin packaging and transcriptional activity.

The four histones of the nucleosome core particle are all subject to enzyme-catalysed, post-translational acetylation at defined lysine residues in their amino-terminal domains. Much circumstantial evidence suggests a role for this process in modifying chromatin structure and function, but detailed mechanisms have not been defined. To facilitate studies on the functional significance of histone acetylation, we have prepared antibodies specific for the acetylated isoforms of histone H4. Because of the extreme evolutionary conservation of H4, these antisera can be applied to a wide variety of organisms and experimental systems. In the present study we have used polytene chromosomes from the salivary glands of larvae of the midge Chironomus to examine the distribution of acetylated H4 in interphase chromatin. By indirect immunofluorescence, antisera to acetylated H4 labeled the four Chironomus chromosomes with reproducible patterns of sharply defined, fluorescent bands. An antiserum to non-acetylated H4 gave a completely different, more-diffuse labelling pattern. Thus, there are defined regions, or islands, in the interphase genome that are enriched in acetylated H4. Double-labelling experiments with two antisera specific for H4 molecules acetylated at different sites, showed that each antiserum gave the same banding pattern. Immunolabelling patterns were not dependent on the pattern of phase-dense bands characteristic of these chromosomes; strongly labelled regions could correspond to phase-dense bands (i.e. condensed chromatin), to interbands or, frequently, to band-interband junctions. Immunogold electron microscopy confirmed the immunofluorescence results and showed further that regions of relatively high labelling could be either transcriptionally active or quiescent, as judged by the presence or absence of ribonucleoprotein particles. Two rapidly transcribed genes on chromosome 4 of Chironomus form characteristic 'puffs', the Balbiani rings BRb and BRc. The antiserum to non-acetylated H4 gave diffuse labelling throughout these puffs, demonstrating the continued presence of this histone in these transcriptionally active regions. Antisera to acetylated H4 strongly labelled the boundaries of BRb and BRc, and revealed clearly defined islands of increased H4 acetylation just within the expanded chromatin of the puffs. Labelling within the central region of each puff was much less intense. A similar pattern was observed in puffs on other chromosomes. Thus, increased H4 acetylation is not found throughout actively transcribed chromatin but occurs only at defined sites, possibly in the non-transcribed flanking regions. H4 acetylation is clearly not required for the passage of RNA polymerase through the nucleosome and we speculate that its role may be to facilitate the binding to DNA of polymerases and other proteins prior to the onset of transcription and possibly replication.

Acetylation↗
PubMed1986

Comparative evaluation of New York City and modified Thayer-Martin media for isolation of Neisseria gonorrhoeae.

Commercially manufactured New York City (NYC) medium and modified Thayer-Martin (MTM) medium were compared for their ability to isolate Neisseria gonorrhoeae from clinical specimens. Twenty-seven public health laboratories throughout California evaluated 4,802 specimens collected from patients attending either sexually transmitted disease or family planning clinics. Total of 726 and 737 N. gonorrhoeae isolates were recovered from NYC and MTM medium, respectively. Although less contamination was noted on NYC medium, MTM medium was equivalent to commercially prepared NYC medium for the isolation of N. gonorrhoeae from clinical specimens.

Cervix Uteri↗
PubMed1985

Reliability study of detection of somatic dysfunctions in the cervical spine.

A reliability study was conducted to determine whether palpatory findings on the cervical spine, obtained under normal chiropractic clinical conditions were reproducible. Forty normal freshman chiropractic students underwent static and motion palpation of their cervical spines by three different chiropractors. Intra- and inter-examiner reliability of findings was assessed by concordance statistics (weighted kappa). There was statistically significant agreement of findings for all three examiners only for fixations in the lower cervical spine. There was a total lack of statistical agreement of fixation findings, both intra- and inter-examiner, in the middle cervical area. Agreement of fixation findings was intermediate for the upper cervicals and also for the other palpation parameters that were used (e.g. muscle spasms and pain) throughout the cervical spine. The results generally indicate a relatively high level of replicability of palpatory findings in a normal asymptomatic population by 'typical' chiropractors. The relation of these palpatory findings to vertebral lesions, or subluxations, are unknown.

Cervical Vertebrae↗