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Biomedical subjects

J M Adams

Publications and source records attributed to J M Adams.

At least 127 records · Page 7Linked to original sources

Variable tolerance of the developing follicle and corpus luteum to gonadotropin-releasing hormone antagonist-induced gonadotropin withdrawal in the human.

To examine the differential sensitivity of the ovary to temporary withdrawal of gonadotropin support at different stages of folliculogenesis and corpus luteum function, GnRH antagonist blockade of gonadotropin secretion was examined in 17 studies using the Nal-Glu GnRH antagonist. A vehicle control, antagonist treatment, and follow-up cycle format was used in each study. A previously determined ED100 dose of the Nal-Glu GnRH antagonist (150 micrograms/kg) or vehicle was administered sc every 24 h for 3 consecutive days in the midfollicular phase (MFP), late follicular phase (LFP), and midluteal phase (MLP). In studies in the MFP (n = 7), the largest follicle was 11 +/- 2 mm (mean +/- SEM), and the mean estradiol (E2) level was 220 +/- 44 pmol/L on the first day of antagonist administration. Administration of the antagonist resulted in a 75 +/- 6% suppression of LH (P less than 0.005), no significant change in FSH, and suppression of E2 to the assay detection limit (P less than 0.05). Total cycle length was increased compared to that of the vehicle control cycle (37.3 +/- 1.3 vs. 26.3 +/- 1.1 days; (P less than 0.005) due to prolongation of follicular phase length (P less than 0.005) and reinitiation of folliculogenesis. In the LFP (n = 5), the largest follicle was 16 +/- 1 mm (P less than 0.05 vs. MFP), and the E2 level was 394 +/- 95 pmol/L (P less than 0.05 vs. MFP) on the first day of antagonist administration. Antagonist administration resulted in a 65 +/- 6% suppression of LH (P less than 0.05), a 47 +/- 11% decrease in FSH (P less than 0.05), and no significant change in E2. Total cycle length was prolonged (32.4 +/- 2.2 vs. 25.6 +/- 0.4 days; P less than 0.05) due to an increase in follicular phase length (P less than 0.02); however, the prolongation of the follicular phase was significantly less than that of the MFP (8.0 +/- 1.5 vs. 15.1 +/- 0.1 days; P less than 0.001), suggesting ovulation from the initial dominant follicle. In studies in the MLP (n = 5), LH, E2, and progesterone decreased to the assay detection limit after antagonist administration, while FSH decreased by 36 +/- 4% (P less than 0.05). Menstrual bleeding occurred within 24-48 h of the final Nal-Glu antagonist injection.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Differential expression of the LYL, SCL and E2A helix-loop-helix genes within the hemopoietic system.

The helix-loop-helix genes LYL, SCL and E2A are associated with chromosome translocations found in human lymphoid leukemias. To establish their hematopoietic expression patterns, we have isolated murine LYL and SCL cDNA clones and investigated the expression of all three genes by Northern blot analysis of 58 murine hemopoietic cell lines and tissues. The nucleotide sequences of LYL cDNA clones revealed alternative 5' untranslated sequences and differential splicing within the 5' portion of the coding region that may produce a LYL polypeptide lacking an N-terminal segment. The LYL gene was expressed in most myeloid, erythroid and B lymphocyte cell lines and displayed two alternative size classes of transcripts, the smaller size class (1.5-1.8 kb) being typical of the erythroid lineage and the larger class (2.0-2.3 kb) of the B cell lineage. These two size classes were found to differ in the 5' untranslated region. Thus, expression of the LYL gene appears to be differentially regulated in different hemopoietic cell types. In contrast, the E2A gene was expressed throughout the hemopoietic compartment as a single dominant transcript (3.5 kb). SCL expression was restricted to erythroid, mast and early myeloid cell lines, and the level of SCL transcripts (3.0 and 4.7 kb species) increased markedly during DMSO-induced differentiation of erythro-leukemia cells. Hence the SCL gene product may be an important regulatory factor for the erythroid lineage. The low or undetectable expression of both SCL and LYL in most T lymphoid cell sources is consistent with the view that the translocations of these genes in human T cell leukemias alter their normal regulation and may thereby contribute to neoplasia.

Animals↗

Inhibiting carbonic anhydrase in brain tissue increases the respiratory response to rebreathing CO2.

To determine the respiratory effects of inhibiting carbonic anhydrase in brain tissue, we infused acetazolamide (ACZ) into the cisterna magna in anesthetized rats. Three concentrations, 4.5, 45 and 450 microM in artificial cerebrospinal fluid, were infused continuously at 2 microliter/min for 20 min and the responses to CO2 rebreathing trials were compared to sham CSF infusions without ACZ. Baseline, steady-state respiration during room air breathing was not affected by these doses of ACZ, but the two higher doses increased the minute ventilation rebreathing response. We conclude that inhibition of carbonic anhydrase in brain tissue increases the respiratory response to rebreathing CO2.

Acetazolamide↗

An E mu-v-abl transgene elicits plasmacytomas in concert with an activated myc gene.

To clarify how the v-abl oncogene of Abelson murine leukemia virus contributes to lymphoid tumorigenesis, we introduced the gene linked to an immunoglobulin heavy chain enhancer (E mu) into the mouse germline. Although lymphoid development was not detectably affected in young E mu-v-abl mice, three transgenic lines shared a high predisposition to develop clonal plasmacytomas that secreted IgA or IgG. The unexpected absence of pre-B lymphomas suggests that Abelson virus generates such tumors by infecting an early lymphoid progenitor cell that has not yet activated the heavy chain enhancer. Most plasmacytomas bore a rearranged c-myc gene, apparently as a result of spontaneous translocation to the Igh locus. Moreover, progeny of a cross with analogous E mu-myc mice rapidly developed oligoclonal plasmacytomas. Thus, the collusion of v-abl with c-myc is stage specific, efficiently transforming plasma cells but not pre-B cells or B cells.

Abelson murine leukemia virus↗

Hydrodynamic deposition: a novel method of cell immobilization.

A novel method of cell immobilization is described. The cell support consists of ceramic microspheres of approximately 50-75 microns diameter. The spheres are hollow, having a wall thickness of 10-15 microns and one entrance (ca. 20 microns diameter). The walls are porous with a mean pore size of approximately 90 nm. When a cell suspension (of S. cerevisiae) is passed through a column of such particles, cells are immobilized. Conditions are devised such that the overwhelming majority of cells are held in the central cavity of the support and not between the particles. Provided turbulence is avoided, the distribution of cells along the column length in the steady state is rather homogeneous. The facts that (a) essentially all particles, regardless of orientation, entrap cells, and (b) nonporous particles also entrap cells with high efficiency, indicate that filtration effects are irrelevant and that heretofore unrecognized hydrodynamic forces are alone responsible for the cell immobilization. Cells can be immobilized to high biomass densities, while the hydrodynamic properties of columns containing such immobilized cells are excellent. We describe an on-line electronic method for the real-time measurement of immobilized cellular biomass. Cell growth (so recorded) and metabolism continue to occur in such particles at high rates. Using the glycolytic production of ethanol by S. cerevisiae as a model reaction, volumetric productivities as great as any published are obtained. Thus the "lobster-pot effect" or "hydrodynamic deposition" represents a novel, promising, and generally applicable method of cell immobilization.

Biotechnology↗

Homeobox gene expression plus autocrine growth factor production elicits myeloid leukemia.

In the murine myelomonocytic leukemia WEHI-3B, proviral insertions have induced expression of the Hox-2.4 homeobox gene and the gene for the myeloid growth factor interleukin 3 (IL-3). To assess their potential oncogenic role, normal bone marrow cells were infected with retroviruses bearing the genes for IL-3 or IL-3 plus Hox-2.4. Unlike the IL-3 virus, the IL-3/Hox-2.4 virus was highly leukemogenic. Infected cells expressing both genes exhibited retarded differentiation in vitro, generated myelomonocytic cell lines, and provoked a rapid, transplantable myeloid leukemia in vivo. The oncogenic action of Hox-2.4 appears to derive from its ability to impede the IL-3-driven terminal differentiation of myeloid cells. The results suggest that homeobox genes can regulate key differentiation processes such as self-renewal capacity and that their inappropriate expression can be oncogenic.

Animals↗

Is distal sampling of end-tidal CO2 necessary in small subjects?

The authors compared PaCO2 with end-tidal CO2 (ETCO2) sampled at multiple sites along the endotracheal tube (ETT) in seven anesthetized rabbits (weight, 2.7-3.6 kg) to determine the most convenient, yet accurate, sampling location. Comparisons were made during spontaneous and controlled ventilation with fresh gas flows (FGF) of two and ten times the minute ventilation using a Mapleson D circuit. An Engstrom Eliza analyzer with a continuous sampling rate of 100 ml/min was used to measure ETCO2. A 0.75-mm ID polyethylene tube inserted in the side of the ETT sampled ETCO2 at the distal tip and at the 6-, 12-, and 15-cm marks on the ETT. ETCO2 was also measured at the standard proximal connector. The differences (P less than 0.05) between PaCO2 and ETCO2 at the distal, 6-, 12-, and 15-cm marks were 2.9 +/- 0.4, 3.1 +/- 0.4, 3.6 +/- 0.4, and 4.6 +/- 0.5 mmHg (mean +/- SEM), respectively, and did not change with FGF or mode of ventilation. The difference between PaCO2 and ETCO2 measured at the proximal connector was always large but significantly (P less than 0.05) greater during spontaneous than controlled ventilation (24.2 +/- 1.5 versus 15.0 +/- 1.4 mmHg) and at higher FGF (19.4 +/- 1.3 versus 16.8 +/- 1.6 mmHg). The differences (P less than 0.05) between ETCO2 at the distal tip and ETCO2 at the 6-, 12-, and 15-cm marks were 0.24 +/- 0.07, 0.73 +/- 0.11, and, 1.77 +/- 0.20 mmHg, respectively. This demonstrates that the change in ETCO2 between the distal tip and the 12-cm mark on the ETT is less than 1 mmHg, and that this clinically insignificant difference is independent of FGF and mode of ventilation. The 12 cm-mark is outside of the mouth on a newborn, and sampling ETCO2 at that point, which may be accomplished simply by inserting a small needle in the side of the ETT, may be the most appropriate sampling location.

Analysis of Variance↗

Instrumented gait analysis after selective dorsal rhizotomy.

In an attempt to assess quantitatively the effects of selective dorsal rhizotomy on ambulatory patients with cerebral palsy, instrumental gait analysis was used to document and compare changes following surgery. Stride characteristics, dynamic surface electromyography, foot-floor contact patterns and motion of the thigh, knee and ankle were analysed. 14 patients (seven independent ambulators, seven using assistive devices) aged between 4.6 and 23.5 years were tested before surgery and again six to 14 months later. After surgery, the seven independent walkers retained the same level of function and one of the assisted walkers had progressed to independent walking, but the other six still used the same device as before surgery. Selective dorsal rhizotomy reduces spasticity and improves gait dynamics, but does not change patterns of muscle activation during walking.

Adolescent↗

Videofluoroscopic assessment of muscle fiber shortening in the in situ canine diaphragm.

We tested the hypothesis that dynamic shortening of the costal diaphragm can be accurately estimated from measurements of the radiographic width of the zone of apposition (WZapp) by studying seven supine anesthetized dogs. Both muscle fiber length, represented by the distance between implanted radiopaque markers, and WZapp were measured from digitized recordings of fluoroscopic images utilizing interactive computer software. The WZapp was highly correlated with the length of costal fibers during active respiration in all animals (mean R2 = 0.94). The accuracy in the prediction of fiber length and shortening during breathing is enhanced by inclusion of additional variables describing the displacement of the abdominal wall and the resting geometric orientation of the fibers. We conclude that dynamic fluoroscopic measurement of WZapp is a valuable technique for estimating dynamic diaphragm fiber length and shortening. Depending on the experimental circumstances, WZapp may be a more easily acquired indicator of diaphragm shortening than other variables that have been previously utilized. As such, it may provide a suitable approach to assess active shortening of the diaphragm in humans.

Animals↗

Multicenter trial of single-dose modified bovine surfactant extract (Survanta) for prevention of respiratory distress syndrome. Ross Collaborative Surfactant Prevention Study Group.

A multicenter, prospective randomized controlled trial was performed comparing the efficacy of a single intratracheal dose of modified bovine surfactant extract (Survanta, 100 mg/kg, Abbott Laboratory, North Chicago, IL) with air placebo in preventing respiratory distress syndrome. Infants were enrolled if they were estimated to be between 24 and 30 weeks' gestation, weighed between 750 and 1250 g, and were intubated and stabilized within 15 minutes after birth. A total of 160 infants were treated (79 with surfactant, 81 with air placebo) between 4 and 37 minutes after birth (median time 12 minutes). Of these, 5 infants were excluded from the final analysis. The 72-hour average values for the arterial-alveolar oxygen ratio, fraction of inspired oxygen, and mean airway pressure were calculated from the area under the curve of scheduled values measured throughout 72 hours. Clinical status was classified using five ordered categories (no supplemental oxygen or assisted ventilation, supplemental oxygen only, continuous positive airway pressure or assisted ventilation with intermittent mandatory ventilation less than or equal to 6 breaths/min, assisted ventilation with intermittent mandatory ventilation greater than 6 breaths/min, death). Chest radiographs at 24 hours were graded for severity of respiratory distress syndrome. Infants receiving Survanta had less severe radiographic changes at 24 hours of age and decreased average fraction of inspired oxygen (31% vs 42%, P = .002) compared with control infants. No differences were noted in the average arterial-alveolar oxygen ratio, mean airway pressure, or clinical status on days 7 and 28. A beneficial effect was noted in the incidence of pneumothorax (P = .057) and an increase was noted in the incidence of necrotizing enterocolitis (P = .052). No differences in incidence of patent ductus arteriosus, intraventricular hemorrhage, sepsis, or bronchopulmonary dysplasia were seen. According to results of a secondary analysis, there was improvement in the fraction of inspired oxygen and a greater number of survivors without bronchopulmonary dysplasia in the subgroup of infants weighing less than 1000 g who were treated with surfactant. It was concluded that a single dose of Survanta given shortly after birth resulted in decreased severity of chest radiographic findings 24 hours after treatment and improved oxygenation during 72 hours after treatment, but did not improve other acute measures of disease severity or clinical status later in the neonatal period. The group at highest risk for respiratory distress syndrome (infants with birth weights between 750 and 999 g) may benefit the most from preventive therapy.

Animals↗

Expression of Hox-2.4 homeobox gene directed by proviral insertion in a myeloid leukemia.

The presence of an altered Hox-2.4 gene in the WEHI3B murine myeloid leukemia suggests that homeobox genes may contribute to neoplasia. A survey of 31 leukemia cell lines of the myeloid, lymphoid and erythroid lineages revealed that Hox-2.4 was expressed only in WEHI3B and the pre-B lymphoid line 70Z/3, in which no DNA rearrangement was observed. To clarify the WEHI3B alteration and normal Hox-2.4 structure, we have sequenced near full length cDNA clones from WEHI3B and 70Z/3, and the 5' portion of the normal Hox-2.4 gene. A WEHI3B cDNA clone demonstrates that an intracisternal A-particle (IAP) provirus has inserted within the first exon of the gene and generated a Hox-2.4 mRNA with a 5' sequence derived from the IAP long terminal repeat. A remarkable degree of similarity found between the amino acid sequences of Hox-2.4 and Hox-3.1, which reside on different chromosomes, supports the notion that an ancient homeobox gene cluster has been duplicated and dispersed early in vertebrate evolution.

Amino Acid Sequence↗

Tracheal agenesis. A case report and literature review.

Tracheal agenesis (TA) is a rare congenital anomaly that is incompatible with prolonged life. It occurs in isolation or in association with other anomalies. The affected neonate presents with respiratory distress and is unable to produce an audible cry despite obvious physical effort. A difficult intubation ensues, and often only during a postmortem examination is the diagnosis of TA made. It is hoped that in addition to adding the 47th case of TA to the literature, this article will provide some insight into the pathogenesis, presentation, and management of this anomaly. It must be emphasized that as TA carries a fatal prognosis, great care must be taken in establishing the diagnosis. If the diagnosis is confirmed, complex reconstructive surgery is not recommended as it has not been shown to change the prognosis or clinical course of affected neonates.

Euthanasia, Passive↗

Lymphoid neoplasia and the control of haemopoietic differentiation.

Our broad aims are to delineate oncogenic events in lymphoid neoplasia and to search for genes that control haemopoietic differentiation. To explore lymphoid neoplasia, we have constructed transgenic mice bearing different oncogenes coupled to the immunoglobulin heavy chain enhancer (E mu), to force expression within lymphocytes. The prototype E mu-myc mice are highly prone to lymphomagenesis, generating pre-B and B cell lymphomas. In their pre-neoplastic phase, E mu-myc expression perturbs B cell development, accelerating the accumulation of pre-B cells. Lymphomagenesis requires additional oncogenic events, such as ras activation, and can be reconstructed in vitro. Transgenic mice bearing the N-myc, N-ras, v-abl and bcr-v-abl oncogenes are also prone to tumours. A striking demonstration that oncogenes can perturb lineage commitment has emerged. Introduction of the v-raf gene into cloned E mu-myc transgenic B cells frequently led to a switch in haemopoietic lineage: the cells became macrophages. Two clues to this remarkable metamorphosis are that the macrophage lines produce a myeloid growth factor and most bear marked karyotypic alterations, perhaps indicating that the balance between a few critical lineage control genes has been disturbed. To explore the hypothesis that genes encoding the DNA-binding homeo box domain participate in haemopoiesis, cDNA libraries from haemopoietic sources were screened, and several distinct homeo box cDNAs were isolated. They revealed a complex pattern of expression among haemopoietic cell lines. These genes are attractive candidates for regulators of haemopoietic differentiation.

Animals↗

N-myc transgene promotes B lymphoid proliferation, elicits lymphomas and reveals cross-regulation with c-myc.

To assess the impact of constitutive N-myc expression on lymphocytes, we generated lines of transgenic mice bearing the murine N-myc oncogene coupled to the immunoglobulin heavy chain enhancer (E mu). As in mice carrying an analogous c-myc construct, E mu-N-myc mice exhibit a limited overgrowth of cycling pre-B cells and eventually succumb to clonal B lymphoid tumours. The endogenous N-myc and c-myc alleles are silent in both E mu-N-myc and E mu-myc lymphomas, suggesting that these genes are subject to auto- and cross-regulation. The regulatory interaction and the similar biological effects of N-myc and c-myc imply that the two genes perform interchangeable functions in the promotion of cell proliferation.

Animals↗