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J M Adams

Publications and source records attributed to J M Adams.

At least 73 records · Page 4Linked to original sources
PubMed1998

Nitric oxide synthase inhibitors alter ventilation in isoflurane anesthetized rats.

BACKGROUND: Nitric oxide (NO) is present in medullary structures and can modulate respiratory rhythm. The authors determined if spontaneous ventilation at rest and in response to increased carbon dioxide is altered by selective neuronal NO synthase (NOS; 7-nitro-indazole, 7-NI) or nonselective (neuronal plus endothelial) NOS (NG-L-arginine methyl ester [L-NAME] and NG-monomethyl L-arginine [L-NMMA]) inhibitors in rats anesthetized with isoflurane. METHODS: Fifty-four rats received either L-NAME or L-NMMA (1, 10, and 30 mg/kg) or 7-NI (20, 80, and 400 mg/kg) and were compared with time controls (isoflurane = 1.4%), with isoflurane concentrations (1.6%, 1.8%, and 2%) increased consistent with the increased anesthetic depth caused by NOS inhibitors, or with L-arginine (300 mg/kg). Tidal volume (VT), respiratory frequency (f), minute ventilation (VE), and ventilatory responses to increasing carbon dioxide were determined. RESULTS: L-NAME and L-NMMA decreased resting VT and VE, whereas 7-NI had no effect. Increasing concentrations of isoflurane decreased resting f, VT, and VE. L-NAME and L-NMMA decreased VT and VE, whereas 7-NI had no effect at 8%, 9%, and 10% end-tidal carbon dioxide (ETCO2). Increasing concentrations of isoflurane decreased f, VT, and VE at 8%, 9%, and 10% ETCO2. The slope of VE versus ETCO2 was decreased by isoflurane but was unaffected by L-NAME, L-NMMA, or 7-NI. L-arginine alone had no effect on ventilation. CONCLUSIONS: Nonselective NOS inhibitors decreased VT and VE at rest and at increased carbon dioxide levels but did not alter the slope of the carbon dioxide response. Selective neuronal NOS inhibition had no effect, suggesting that endothelial NOS may be the isoform responsible for altering ventilation. Finally, the cause of the decreased ventilation is not a result of the enhanced anesthetic depth caused by NOS inhibitors.

Anesthesia, Inhalation↗
PubMed1998

Zalcitabine population pharmacokinetics: application of radioimmunoassay.

Zalcitabine population pharmacokinetics were evaluated in 44 human immunodeficiency virus-infected patients (39 males and 5 females) in our immunodeficiency clinic. Eighty-one blood samples were collected during routine clinic visits for the measurement of plasma zalcitabine concentrations by radioimmunoassay (1.84+/-1.24 samples/patient; range, 1 to 6 samples/patient). These data, along with dosing information, age (38.6+/-7.13 years), sex, weight (79.1+/-15.0 kg), and estimated creatinine clearance (89.1+/-21.5 ml/min), were entered into NONMEM to obtain population estimates for zalcitabine pharmacokinetic parameters. The standard curve of the radioimmunoassay ranged from 0.5 to 50.0 ng/ml. The observed concentrations of zalcitabine in plasma ranged from 2.01 to 8.57 ng/ml following the administration of doses of either 0.375 or 0.75 mg. A one-compartment model best fit the data. The addition of patient covariates did not improve the basic fit of the model to the data. Oral clearance was determined to be 14.8 liters/h (0.19 liter/h/kg; coefficient of variation [CV] = 23.8%), while the volume of distribution was estimated to be 87.6 liters (1.18 liters/kg; CV = 54.0%). We were also able to obtain individual estimates of oral clearance (range, 8.05 to 19.8 liters/h; 0.11 to 0.30 liter/h/kg) and volume of distribution (range, 49.2 to 161 liters; 0.43 to 1.92 liters/kg) of zalcitabine in these patients with the POSTHOC option in NONMEM. Our value for oral clearance agrees well with other estimates of oral clearance from traditional pharmacokinetic studies of zalcitabine and suggests that population methods may be a reasonable alternative to these traditional approaches for obtaining information on the disposition of zalcitabine.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Relationship between didanosine exposure and surrogate marker response in human immunodeficiency virus-infected outpatients.

We used information available from routine clinic visits to characterize the pharmacokinetics of didanosine in 82 human immunodeficiency virus-infected patients. A total of 271 blood samples were collected for the measurement of didanosine concentrations in plasma (mean +/- standard deviation [SD], 3.30 +/- 2.21 samples/patient). Bayesian estimates of didanosine oral clearance (CL[oral]) were obtained for these patients by the POSTHOC option within the NONMEM software package. Population priors from a previous NONMEM analysis of didanosine pharmacokinetics were used. The mean +/- SD CL(oral) was 132 +/- 27.7 liters/h, which agrees reasonably well with estimates obtained from previous pharmacokinetic studies of didanosine. Estimates of individual didanosine exposure were then used to consider potential relationships between drug exposure and surrogate marker response over a 6-month period. No correlations were found between the didanosine area under the concentration-time curve from 0 to 6 months and the absolute CD4 cell count (r = 0.305; 0.1 < P < 0.2), weight response (r = 0.0857; P > 0.4), or percentage of CD4 lymphocytes (r = 0.0559; P > 0.4). Future efforts to characterize didanosine exposure in outpatients by random sampling methods should involve more directed efforts to limit residual variability in the data.

Adult↗
PubMed1998

Actuarial survival in the premature infant less than 30 weeks' gestation.

OBJECTIVE: Because survival from admission to discharge does not provide parents and physicians information about future life expectancy in the premature neonate, we characterized the actuarial survival, defined as the future life expectancy from a given postnatal age, in a large inborn population of premature infants < 30 weeks' gestation. STUDY DESIGN: We determined daily actuarial survival of 1925 inborn infants (23 to 29 weeks' gestation) admitted to the Baylor Affiliated Nurseries from July 1986 through December 1994, stratified by 100-g birth weight and by 1-week gestational-age intervals. RESULTS: In the 501- to 600-g birth weight stratum, actuarial survival improved from 31% at birth, to 61% on day of life 7, and then to 75% on day of life 28; in the 901- to 1000-g birth weight stratum, actuarial survival improved from 88%, to 94%, and then to 98% throughout the same times, respectively. Similar trends were obtained when data were stratified by gestational age. CONCLUSIONS: Survival in the smallest infants improves dramatically during the first few days of life, but there is a significant risk for late death in the smallest of these infants.

Actuarial Analysis↗
PubMed1997

Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome.

UNLABELLED: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of reproductive age women characterized in its broadest definition by the presence of oligoamenorrhea and hyperandrogenism and the absence of other disorders. Defects of gonadotropin secretion, including an elevated LH level, elevated LH to FSH ratio, and an increased frequency and amplitude of LH pulsations have been described, but the prevalence of these defects in a large, unbiased population of PCOS patients has not been determined. Sixty-one women with PCOS defined by oligomenorrhea and hyperandrogenism and 24 normal women in the early follicular phase had LH samples obtained every 10 min for 8-12 h. Pool LH levels from the frequent sampling studies were within the normal range in the 9 PCOS patients (14.8%) who were studied within 21 days after a documented spontaneous ovulation. Excluding these post-ovulatory patients, 75.0% of the PCOS patients had an elevated pool LH level (above the 95th percentile of the normal controls), and 94% had an elevated LH to FSH ratio. In the anovulatory PCOS patients, pool LH correlated positively with 17-OH progesterone (R = 0.30, P = 0.03), but not with estradiol, estrone, testosterone, androstenedione, or DHEA-S. Pool LH and LH to FSH ratio correlated positively with LH pulse frequency (R = 0.40, P = 0.004 for pool LH, and R = 0.39; P = 0.005 for LH/FSH). There was also a strong negative correlation between pool LH and body mass index (BMI) (R = -0.59, P < 10(-5)). The relationship between BMI and LH secretion in the PCOS patients appeared to be strongest with body fatness, as pool LH was correlated inversely with percent body fat, whether measured by skinfolds (R = -0.61, P < 10(-5)), bioimpedance (R = -0.55, P < 10(-4)), or dual energy x-ray absorptiometry (DEXA) (R = -0.70, P = 0.001; n = 18 for DEXA only). By DEXA, the only body region that was highly correlated with pool LH was the trunk (R = -0.71, P = 0.001). The relationship between body fatness and LH secretion occurred via a decrease in LH pulse amplitude (R = -0.63, P < 10(-5) for BMI; R = -0.58, P < 10(-4) for bioimpedance; and R = -0.64, P = 0.004 for whole body DEXA), with no significant change in pulse frequency with increasing obesity (R = -0.17, P = 0.23 for BMI). IN CONCLUSION: 1) the prevalence of gonadotropin abnormalities is very high in women with PCOS selected on purely clinical grounds, but is modified by recent spontaneous ovulation; 2) the positive relationship between LH pulse frequency and both pool LH and LH to FSH ratio supports the hypothesis that a rapid frequency of GnRH secretion may play a key etiologic role in the gonadotropin defect in PCOS patients; 3) pool LH and LH pulse amplitude are inversely related to body mass index and percent body fat in a continuous fashion; and 4) the occurrence of a continuous spectrum of gonadotropin abnormalities varying with body fat suggests that nonobese and obese patients with PCOS do not represent distinct pathophysiologic subsets of this disorder.

Adolescent↗
PubMed1997

Resource utilization among neonatologists in a university children's hospital.

OBJECTIVE: We studied factors affecting length of hospital stay and resulting hospital charges among patients managed by two separate groups of neonatologists in the same academic health science center. DESIGN: Retrospective analysis of clinical and financial data base information. METHODS: Neonatal intensive care was provided in the same acute care nursery in a large university children's hospital by: (1) neonatologists in a full-time academic division (group A) and (2) a group associated with a private managed care organization (group B). Clinical and financial parameters of all neonates admitted in fiscal year 1994 were compared for the two provider groups. Stepwise regression analysis was used to evaluate factors influencing hospital charges and length of hospital stay (LOS) and to adjust for differences in clinical variables between the two groups. RESULTS: Group A physicians provided care for 340 infants, while 137 were treated by those of group B. Group A included older patients, more outborns, more level III patients, more sepsis, more intermittent positive pressure ventilation, and more patent ductus arteriosus. The incidence of transient tachypnea of the newborn was higher among group B patients. Hospital charges were primarily determined by LOS, which was similar for the two groups. When the data were corrected for differences in risk and patient acuity, however, a significant relationship between physician group and LOS was demonstrated, with LOS being an average of 7.8 days shorter for group A. A net reduction of $3 114 969 in hospital charges might have been realized had group A physicians provided care for all study patients. CONCLUSIONS: Hospital charges were determined by LOS. In this setting, academic neonatologists produced shorter LOS and comparable clinical outcomes, despite caring for a population at greater risk. The reduction in LOS could have resulted in more than $3.1 million in annualized savings had the academic group provided care for all of the study patients.

Analysis of Variance↗
PubMed1996

Bcl-2 has a cell cycle inhibitory function separable from its enhancement of cell survival.

Myeloid maturation appears to require exit from the cell cycle and leads to activation of apoptosis in the differentiated cells. The level of Bcl-2, which is known to promote cell survival, is shown here to influence both these critical steps. Bcl-2 function during myelomonocytic differentiation was investigated by introducing a deregulated bcl-2 gene into HL60 promyelocytic leukemia cells, which can be induced to exit the cell cycle and differentiate into granulocytes or monocytes. Deregulated Bcl-2 expression did not itself promote differentiation but extended the lifespan of mature cells elicited by granulocytic or monocytic inducers. Unexpectedly, in response to induction, Bcl-2 overexpression markedly potentiated and hastened cell cycle withdrawal into G(0). Enhanced survival cannot account for the elevated numbers of G(0) cells, because they arose under induction conditions that did not kill control cells. Since the cell cycle status and growth of uninduced cells was not affected by Bcl-2-overexpression, its cell cycle inhibitory activity must require an induction signal. While cell cycle withdrawal may be necessary for maturation, it was not sufficient, implicating a requirement for specific differentiative signals. These results identify, for the first time, a function for the bcl-2 proto-oncogene that is separable from its enhancement of cell survival.

Cell Cycle↗
PubMed1996

bcl-w, a novel member of the bcl-2 family, promotes cell survival.

The prototypic mammalian regulator of cell death is bcl-2, the oncogene implicated in the development of human follicular lymphoma. Several homologues of bcl-2 are now known. Using a PCR-based strategy we cloned a novel member of this gene family, denoted bcl-w. The gene, which is highly conserved between mouse and human, resides near the T-cell antigen receptor alpha gene within the central portion of mouse chromosome 14 and on human chromosome 14 at band q11. Enforced expression of bcl-w rendered lymphoid and myeloid cells refractory to several (but not all) cytotoxic conditions. Thus, like Bcl-2 and Bcl-x, the Bcl-w protein promotes cell survival, in contrast to other close homologues, Bax and Bak, which facilitate cell death. Comparison of the expected amino acid sequence of Bcl-w with that of these relatives helps to delineate residues likely to convey survival or anti-survival function. While expression of bcl-w was uncommon in B or T lymphoid cell lines, the mRNA was observed in almost all murine myeloid cell lines analysed and in a wide range of tissues. These findings suggest that bcl-w participates in the control of apoptosis in multiple cell types. Its functional similarity to bcl-2 also makes it an attractive candidate proto-oncogene.

Amino Acid Sequence↗
PubMed1996

Hlx homeo box gene is essential for an inductive tissue interaction that drives expansion of embryonic liver and gut.

The divergent murine homeo box gene Hlx is expressed in restricted hematopoietic cell types and, during embryogenesis, prominently in visceral mesenchyme of the developing liver, gall bladder, and gut. Targeted disruption of the gene has now established that it plays a key role in visceral organogenesis. Embryos homozygous for the mutation died around embryonic day 15 with anemia and severe hypoplasia of the liver and gut. Liver ontogeny commenced normally with formation of the liver diverticulum and differentiation of hepatocytes, but the organ failed to expand and reached only 3% of normal size. The apparent liver hypoplasia was not associated with a notable increase in apoptotic cells. Gut development also began normally, but the intestines failed to undergo extensive elongation and looping and reached only a quarter of normal length. The anemia resulted from a deficiency in the fetal form of hematopoiesis, which occurs in the liver, but no intrinsic defect in Hlx-/- hematopoietic cells was observed in vitro, and liver-derived Hlx-/- hematopoietic stem cells that were transplanted to irradiated normal mice could fully reconstitute hematopoiesis. The impaired fetal hematopoiesis therefore reflects insufficient support function provided by the minute liver. Hlx is normally expressed in visceral mesenchyme lying adjacent to the developing liver and gut epithelia affected by the mutation, but not in the epithelia themselves. Hence, Hlx regulates a mesenchymal-epithelial interaction that drives a vital growth phase in visceral organogenesis. Moreover, because mutation of Hlx blocked liver growth but not its specification, early morphogenesis, or differentiation, development of this organ appears to occur by step-wise inductive interactions under separate genetic control.

Animals↗
PubMed1996

The assessment of trust orientation.

The development of the Trust Inventory, a 40-item measure of trust in generalized others (Generalized Trust) and romantic partners (Partner Trust) is described. A third conceptualization of trust in friends and family members (Network Trust) is also discussed College students (N = 1,229) participated in five stages of test construction and validation. Results indicated that the Trust Inventory scales are reliable, both internally and temporally, and that the Partner Trust and Generalized Trust Scales demonstrate both concurrent and construct validity. The resulting inventory is unique in its capacity to assess these types of trust simultaneously. Evidence supporting the discriminant validity of the Network Trust was mixed, whereas factor analytic treatments of Trust Inventory items supported the distinctiveness of Network Trust as compared to Partner and Generalized Trust, the Network Trust Scale correlated to roughly the same degree as the other two scales with several variables of differential theoretical relevance. Thus, little evidence supporting the incremental validity of Network Trust was observed Discussion focuses on the evidence suggesting the validity of interpretations of Generalized and Partner Trust and considers the issue of additional research regarding Network Trust.

Journal Article↗
PubMed1996

A randomized, controlled trial of estradiol replacement therapy in women with hypergonadotropic amenorrhea.

Premature ovarian failure is classically defined as menopause occurring before age 40 and is associated with elevated serum FSH levels. If elevated FSH levels indicate lack of ovarian feedback and depletion of primordial follicles, women with prematurely elevated FSH levels should have infertility. However, there are many reports of pregnancies in affected women occurring during estrogen therapy leading to the hypothesis that estrogen may have a salutary effect on folliculogenesis and conception. This randomized, controlled trial was designed to investigate whether estrogen replacement therapy offered a significant therapeutic benefit in hypergonadotropic amenorrhea and to evaluate the potential pathophysiologic mechanisms that would explain the reported pregnancies. Thirty seven women, aged 16 to 40, with menstrual dysfunction and documented FSH levels elevated above the 95% confidence limits of the mid-cycle gonadotropin peak of the normal menstrual cycle (> 40 IU/L 2nd IRP hMG in our RIA) on at least two occasions, entered the study. The average duration of their amenorrhea was 15.9 months (range 2-96 months). Subjects were randomized to begin estradiol replacement (micronized estradiol [Estrace TM], 2 mg orally each day) or no therapy for 6 weeks in a 12-week, cross-over design with weekly monitoring by both pelvic ultrasonography and serum hormone levels. Thirty-one women completed the entire randomized study. As expected, estradiol therapy increased mean serum estradiol levels by 98 pg/mL and was associated with a significant decrease in mean LH and FSH levels (LH: 45.4 IU/L 2nd IRP hMG vs. 37.1 IU/L, FSH: 63.4 IU/L vs. 40.6 IU/L, geometric means). However, there was no effect of estradiol replacement on mean ovarian volume, the number or size of new follicles, or the ovulation rate in all subjects or in the subset with no identified cause for their hypergonadotropic hypogonadism (n = 20). Two pregnancies occurred during the randomized trial, one on and one off estradiol. In both arms of the study, the majority of subjects developed cystic ovarian structures by ultrasound that were temporally associated with increasing serum estradiol levels, indicating functional ovarian follicles. Seventy-eight percent of all subjects grew at least one new follicle over 10 mm in diameter and 46% ovulated at least once, as determined by a serum progesterone level more than 4 ng/mL. Although ovulations were significantly more common in the 10 women subjects who had less than 3 months of amenorrhea (all of whom ovulated) than in the 27 with greater than 3 months of amenorrhea (only 7 of whom ovulated (26%), P < 0.001), there was no significant difference in eventual pregnancies (2 of the 10 women with less than 3 months of amenorrhea vs. 3 of the 27 with greater than 3 months of amenorrhea, P = 0.47). We conclude that in hypergonadotropic women with amenorrhea: 1) folliculogenesis occurs often but is less frequently followed by ovulation and rarely by pregnancy, suggesting that elevated FSH is a marker of oocyte dysfunction occurring distinct from and earlier than granulosa cell or follicular dysfunction; and 2) estrogen therapy does not improve the rate of folliculogenesis or ovulation.

Adolescent↗
PubMed1996

Lessons from bcl-2 transgenic mice for immunology, cancer biology and cell death research.

The protein product of the proto-oncogene bcl-2, originally discovered by virtue of its chromosomal translocation in human follicular centre B cell lymphoma, is a physiological inhibitor of programmed cell death, apoptosis. Initial studies in transgenic mice overexpressing Bcl-2 in B or T lymphocytes demonstrated that Bcl-2 can potently antagonise cell death induced by multiple independent signal transduction routes and can contribute to oncogenesis, particularly in combination with other oncogenes, like c-myc, that promote cell proliferation. Further investigations using crosses between bcl-2 transgenic mice and T cell receptor or immunoglobulin transgenic mice or mutant mice deficient in proper antigen receptor gene rearrangement demonstrated that Bcl-2 can only block death of cells that failed to receive a positive stimulus, "death by neglect', but not activation induced apoptosis. Collectively, these results provide evidence that distinct signalling pathways for apoptosis converge upon a common effector machinery where Bcl-2 acts as an antagonist, but that there also exists a mechanism that can either bypass the Bcl-2 checkpoint or override its protective function. These experimental data are reviewed here and discussed in context of current knowledge of lymphocyte differentiation, tumorigenesis and cell death regulation.

Animals↗
PubMed1996

Comparison of the Omron HEM-713C automated blood pressure monitor with a standard ausculatory method using a mercury manometer.

OBJECTIVES: To compare the Omron HEM-713C automated blood pressure machine with the standard ausculatory method using a mercury manometer. DESIGN: Blood pressures of randomly selected subjects were measured using both the Omron HEM-713C and the mercury manometer. SETTING: Dombotombo surburb in Marondera, Zimbabwe. SUBJECTS: One hundred and sixteen subjects 25 years and above (47 males and 69 females) randomly selected in Marondera. MAIN OUTCOME MEASURE: Systolic blood pressure and diastolic blood pressure. RESULTS: The Omron HEM-713C passed with a grade B for both systolic and diastolic blood pressures when using the British Hypertension Society protocol. It also passed both systolic and diastolic criteria for Association of the Advancement of Medical Instrumentation. CONCLUSION: The Omron HEM-713C compares well with the standard mercury manometer, we therefore recommend its use in both research and clinical applications which require blood pressure measurements.

Auscultation↗
PubMed1995

Absence of p53 allows direct immortalization of hematopoietic cells by the myc and raf oncogenes.

The p53 tumor suppressor is implicated here as a crucial barrier to unlimited cell proliferation. Its role in transformation of hematopoietic cells was studied by infecting fetal liver cells from wild-type or p53-/- mice with oncogenic retroviruses. Transformed colonies arose with a raf and a myc-raf virus. Absence of p53 did not affect their frequency but proved critical for their continued propagation. Colonies of p53-/- cells bearing both myc and raf readily yielded continuous cell lines without apparent requirement for genetic alteration. The lines, mainly of erythroid or myelomonocytic origin, were diploid but highly tumorigenic from their inception. These findings imply that p53 loss contributes directly to immortalization and tumorigenesis, probably by abrogating an intrinsic senescence program.

Animals↗
PubMed1995

Overexpressed max is not oncogenic and attenuates myc-induced lymphoproliferation and lymphomagenesis in transgenic mice.

The cellular growth promoting function of the Myc oncoprotein requires its heterodimerization with the Max protein, but Max can also form complexes that inhibit Myc action. To determine whether max overexpression in vivo is oncogenic and whether it can modulate the action of Myc, we generated transgenic mice in which the max gene was directed to express in lymphoid cells by a linked immunoglobulin heavy chain enhancer (E mu). Expression of the transgene at substantially higher levels than the endogenous max gene did not perturb lymphoid homeostasis in adult animals nor predispose to lymphomagenesis. The numbers of B-lymphoid cells in very young animals were reduced. Moreover, analysis of bi-transgenic E mu-myc/E mu-max mice revealed that max overexpression attenuated the premalignant B-lymphoproliferative state induced by an E mu-myc transgene and reduced the rate of lymphoma onset. These results suggest that elevation of Max expression in vivo inhibits the function of Myc.

Animals↗
PubMed1995

Perturbed development of T and B cells in mice expressing an Hlx homeobox transgene.

Within the lymphoid compartment of mice, the Hlx homeobox gene is expressed only at early stages of B-lymphoid differentiation. To determine whether Hlx influences lymphopoiesis, transgenic mice were developed to enforce Hlx expression throughout the B and T cell lineages. The strain with the highest transgene expression in both cell types (Hlx-94) exhibited marked perturbations in both B and T cell development. In these mice, the thymus lacked almost all mature CD4+8- and CD8+4- cells and the medulla was greatly shrunken, whereas nearly one-half the T cells in the periphery were CD4+8+, a cell type normally confined to the thymus. The peripheral CD4+8+ cells had some features of mature T cells, including responsiveness to mitogens. Presumably these cells had emigrated prematurely from the thymus and generated mature T cells in the periphery. Bone marrow transplantation experiments indicated that the defects was intrinsic to the Hlx-94 hematopoietic cells rather than support cells. Although thymocyte development in Hlx-94 mice was blocked at the stage when selection normally occurs, analysis of lymphocyte populations in the progeny of crosses with mice transgenic for an anti-HY T cell receptor indicated that neither positive nor negative selection of T cells was markedly affected. In addition to T cell defects, Hlx-94 mice had subnormal numbers of B lymphoid cells in the bone marrow and spleen, and their surface phenotype suggested that B cell development after the pro-B stage was impeded. Furthermore, the B cell response to stimulation with LPS was impaired. These striking developmental defects suggest that the Hlx gene may help to govern lymphoid maturation.

Animals↗