Cyclin D1 as the putative bcl-1 oncogene.
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Animals↗
Biomedical subjects
J M Adams
Publications and source records attributed to J M Adams.
Comparison of the morbidity associated with maxillary fractures treated by maxillomandibular and rigid internal fixation.
OBJECTIVE: To compare the type and incidence of morbidity encountered by two groups of patients with maxillary fractures, one treated by closed reduction and maxillomandibular fixation and the other by open reduction and rigid internal fixation. STUDY DESIGN: This was a retrospective review of records for all patients with maxillary fractures treated over a 10-year period. Age, sex, mechanism of injury, anatomic location of fracture, treatment modality, and complications were identified. Two populations of patients, those treated with closed reduction and maxillomandibular fixation and those treated with open reduction and rigid internal fixation, that were similar in size (n = 50), age, sex, and anatomic distribution of fractures were compared. RESULTS AND CONCLUSIONS: This study indicates that patients with maxillary fractures treated with either closed reduction and maxillomandibular fixation or open reduction and rigid internal fixation will encounter postoperative problems with a near equal frequency (60% to 64%). Regardless of the technique used, no relationship could be established between age, sex, or cause of injury. The more superior the level of the fracture, the higher the rate of adverse sequelae.
Adolescent↗
Peru-15, an improved live attenuated oral vaccine candidate for Vibrio cholerae O1.
Cholera vaccine candidate Peru-15 was derived from a Vibrio cholerae O1 El Tor Inaba strain by deleting the cholera toxin genetic element, introducing the gene encoding cholera toxin B subunit into recA, and screening for nonmotility. In a controlled study, Peru-15 (2 x 10(8) cfu) was administered to 11 volunteers. No vaccinee developed diarrhea, and 10 of 11 had > 4-fold rises in vibriocidal antibody titers. One month later, 5 vaccinees and 5 control volunteers were challenged with wild type V. cholerae O1. Four of 5 controls developed diarrhea (mean, 1.9 L). Two Peru-15 vaccinees developed diarrhea, 1 with < 0.3 L and 1 with approximately 1.0 L; this latter volunteer had not developed a significant vibriocidal immune response to vaccination. Peru-15 shows promise as a single-dose, oral cholera vaccine that is safe, immunogenic, and protective.
Administration, Oral↗
The C-terminal zinc finger of GATA-1 or GATA-2 is sufficient to induce megakaryocytic differentiation of an early myeloid cell line.
The GATA-1 and GATA-2 transcription factors, which each contain two homologous zinc fingers, are important hematopoietic regulators expressed within the erythroid, mast cell, and megakaryocytic lineages. Enforced expression of either factor in the primitive myeloid line 416B induces megakaryocytic differentiation. The features of their structure required for this activity have been explored. The ability of 12 GATA-1 mutants to promote 416B maturation was compared with their DNA-binding activity and transactivation potential. Differentiation did not require any of the seven serine residues that are phosphorylated in vivo, an N-terminal region bearing the major transactivation domain, or a C-terminal segment beyond the fingers. Removal of a consensus nuclear localization signal following the second finger did not block differentiation or nuclear translocation. The N-terminal finger was also dispensable, although its removal attenuated differentiation. In contrast, the C-terminal finger was essential, underscoring its distinct function. Remarkably, only 69 residues spanning the C-terminal finger were required to induce limited megakaryocytic differentiation. Analysis of three GATA-2 mutants led to the same conclusion. Endogenous GATA-1 mRNA was induced by most mutants and may contribute to differentiation. Because the GATA-1 C-terminal finger could bind its target site but not transactivate a minimal reporter, it may direct megakaryocytic maturation by derepressing specific genes and/or by interacting with another protein which provides the transactivation function.
3T3 Cells↗
Cyclin D1 transgene impedes lymphocyte maturation and collaborates in lymphomagenesis with the myc gene.
Cyclin D1 is the regulatory subunit of certain protein kinases thought to advance the G1 phase of the cell cycle. Deregulated cyclin D1 expression has been implicated in several human neoplasms, most consistently in centrocytic B lymphoma, where the cyclin D1 gene usually has been translocated to an immunoglobulin locus. To determine directly whether constitutive cyclin D1 expression is lymphomagenic, transgenic mice were generated having the cyclin D1 gene linked to an immunoglobulin enhancer. Despite abundant transgene expression, their lymphocytes were normal in cell cycle activity, size and mitogen responsiveness, but young transgenic animals contained fewer mature B- and T-cells. Although spontaneous tumours were infrequent, lymphomagenesis was much more rapid in mice that co-expressed the cyclin D1 transgene and a myc transgene than in mice expressing either transgene alone. Moreover, the spontaneous lymphomas of myc transgenic animals often ectopically expressed the endogenous cyclin D1 gene. These findings indicate that this G1 cyclin can modulate differentiation and collaborate with myc-like genes in oncogenesis.
Animals↗
Cranial fractures associated with facial fractures: a review of mechanism, type, and severity of injury.
A 100-month retrospective review was undertaken to identify the population characteristics of patients with both facial and cranial fractures and to establish the relationships between them. A 4.4% incidence of cranial fractures was found in the 882 patients with facial fractures. These patients tended to be males (85%) between the ages of 16 and 30 years (54%) who were involved in motor vehicle accidents (64%). Patients with midfacial fractures predominated (70%), and these injuries were most frequently associated with fractures of the frontal (38%), sphenoid (24%), or temporal (22%) bones. No relationship was noted between mandibular fractures and cranial fractures. Midfacial fractures were related to individual cranial bone fractures by sutural attachment. The presence of cranial fractures did not play a role in the development of complications associated with facial fractures.
Accidents, Traffic↗
B-lymphoid to granulocytic switch during hematopoiesis in a transgenic mouse strain.
B-lymphoid and myeloid development are markedly perturbed in a unique transgenic mouse strain, max 41. Pro-B, pre-B, and B lymphocytes were severely reduced but granulocytes were greatly elevated. This phenotype could be adoptively transferred with bone marrow cells. It was not alleviated by bcl-2 or myc transgenes that promote lymphocyte survival or proliferation. Bitransgenic myc/max 41 mice developed pre-B cell lymphoma. An accompanying massive granulocytosis unexpectedly proved to be clonally derived from the pre-B lymphoma cells. These observations suggest that B lymphopoiesis in max 41 mice has been diverted to granulocyte production. Since neither cell type expressed the transgene, this novel lymphomyeloid deviation probably reflects insertional alteration of a hematopoietic regulatory gene.
Animals↗
Endotracheal colonization with Candida enhances risk of systemic candidiasis in very low birth weight neonates.
OBJECTIVE: To determine whether growth of Candida from an endotracheal aspirate identifies a population of very low birth weight (VLBW; < or = 1500 gm) neonates at increased risk of systemic candidiasis. DESIGN: Prospective evaluation with weekly cultures of endotracheal and rectal specimens to determine colonization status. SUBJECTS: One hundred sixteen VLBW neonates (mean birth weight, 975 +/- 23 gm, estimated gestational age, 27.6 +/- 0.2 weeks) with endotracheal tubes in place who were admitted to a level III nursery between Jan. 8 and Dec. 2, 1992. RESULTS: Of the 116 subjects, 39 infants were colonized with Candida (34%). Thirteen neonates had growth of Candida in one or more cultures of endotracheal specimens. Eleven of these could be examined, and in five systemic disease developed (disease in 5/11 vs 2/26; relative risk = 5.9; 95% confidence interval, 1.34 to 26). Eight infants were colonized with Candida in the first week of life. Seven of these could be examined, and in five systemic candidiasis developed (disease in 5/7 vs 2/30; RR = 9.3; 95% confidence interval, 2.3 to 38.0). CONCLUSIONS: Colonization with Candida occurs frequently in VLBW infants. Progression from colonization to systemic infection is more common in the smallest neonates. Detection of colonization in the first week of life or the growth of Candida from an endotracheal aspirate identifies a group of VLBW neonates with an endotracheal tube in place whose risk of systemic candidiasis is increased. A prospective trial of intervention in this high-risk population is warranted.
Analysis of Variance↗
Enhanced cell survival and tumorigenesis.
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Animals↗
Acute respiratory acidosis: large-dose furosemide and cerebrospinal fluid ions.
NaCl cotransport carrier is known to be involved in transepithelial fluid absorption and secretion in various tissues. Recent studies indicate that Na-K-2Cl cotransport carrier also exists in the choroid plexus cells and that inhibition of the carrier decreases cerebrospinal fluid (CSF) production. In this study, we used large-dose intravenous furosemide, an inhibitor of Na-K-2Cl carrier, to determine the effects on cisternal CSF ionic composition in acute respiratory acidosis. In pentobarbital-anesthetized mechanically ventilated dogs, renal pedicles were ligated to prevent furosemide-induced diuresis. The experimental group (group II, n = 7) received 400 mg/kg of furosemide intravenously, and group I (control group, n = 7) received the vehicle. In group II, serial serum and CSF furosemide concentrations were approximately 10(-3) and 10(-5) mol/l, respectively. During 5 h of acute respiratory acidosis in both groups, the mean arterial PCO2 increased approximately 25 Torr, with comparable changes in CSF PCO2. In both groups, CSF [HCO3-] and [H+] rose approximately 3 meq/l and 20 neq/l, respectively. Changes in CSF [Na+], [K+], [Cl-], and [Na(+)-Cl-] were also similar and were not significantly different from each other when the two groups were compared. These data show that furosemide at the dose that inhibits NaCl cotransport carrier does not significantly alter ionic composition of cisternal CSF.
Acid-Base Equilibrium↗
Cisternal Na+ transport inhibition and the ventilatory response to CO2.
When PCO2 rises transiently, glia or neurons may move ions across their cell membranes to restore intracellular pH, in the process changing extracellular pH. Inhibiting ion transport would result in a different extracellular fluid pH (a putative stimulus for the medullary chemoreceptors) and, therefore, in an altered ventilation in response to PCO2. We infused two ion transport inhibitors, amiloride and bumetanide, into the cisterna magna of anesthetized rabbits and compared their ventilatory response to a rebreathing maneuver with sham rabbits receiving no inhibitor. Amiloride (10(-5)-10(-3) M) had no effect; 3 h of 10(-2) M amiloride increased the frequency of breathing and decreased tidal volume but had no net effect on minute ventilation. Bumetanide (10(-3) M) had no effect after 1 h of infusion, but by 3 h it had decreased tidal volume and minute ventilation at 6 and 7% end-tidal CO2 fraction, respectively, during the rebreathe. Three hours of infusion of amiloride and bumetanide did not affect ventilation in a manner consistent with our predictions from previous studies of ionic changes in cerebrospinal fluid. During the 1st h, when neuronal and glial ion transport in the ventrolateral medulla should be inhibited, we found no effect of ion transport inhibition. We conclude that, during the transient hypercapnia of a rebreathing maneuver, Na+/H+ exchange and Na(+)-K(+)-2Cl- cotransport do not play a significant role in immediate rapid pH homeostasis by cellular ion transport in the microenvironment of the medullary chemoreceptors.
Amiloride↗
Ventricular proarrhythmic effects of ventricular cycle length and shock strength in a sheep model of transvenous atrial defibrillation.
BACKGROUND: Synchronized cardioversion is generally accepted as safe for the treatment of ventricular tachycardia and atrial fibrillation when shocks are synchronized to the R wave and delivered transthoracically. However, others have shown that during attempted transvenous cardioversion of rapid ventricular tachycardia, ventricular fibrillation (VF) may be induced. It was our objective to evaluate conditions (short and irregular cycle lengths [CL]) under which VF might be induced during synchronized electrical conversion of atrial fibrillation with transvenous electrodes. METHODS AND RESULTS: In 16 sheep (weight, 62 +/- 7.8 kg), atrial defibrillation thresholds (ADFT) were determined for a 3-ms/3-ms biphasic shock delivered between two catheters each having 6-cm coil electrodes, one in the great cardiac vein under the left atrial appendage and one in the right atrial appendage along the anterolateral atrioventricular groove. A hexapolar mapping catheter was positioned in the right ventricular apex for shock synchronization. In 8 sheep (group A), a shock intensity 20 V less than the ADFT was used for testing, and in the remaining 8 sheep (group B), a shock intensity of twice ADFT was used. With a modified extrastimulus technique, a basic train of eight stimuli alone (part 1) and with single (part 2) and double (part 3) extrastimuli were applied to right ventricular plunge electrodes. Atrial defibrillation shocks were delivered synchronized to the last depolarization. In part 4, shocks were delivered during atrial fibrillation. The preceding CL was evaluated over a range of 150 to 1000 milliseconds. Shocks were also delayed 2, 20, 50, and 100 milliseconds after the last depolarization from the stimulus (parts 1 through 3) or intrinsic depolarization (part 4). The mean ADFT for group A was 127 +/- 48 V, 0.71 +/- 0.60 J and for group B, 136 +/- 37 V, 0.79 +/- 0.42 J (NS, P > .15). Of 1870 shocks delivered, 11 episodes of VF were induced. Group A had no episodes of VF in part 1, two episodes of VF in part 2 (CL, 240 and 230 milliseconds with 2-millisecond delay), and one episode each in parts 3 (CL, 280 milliseconds with 2-millisecond delay) and 4 (CL, 240 milliseconds with 100-millisecond delay). Group B had two episodes in part 1 (CL, 250 and 300 milliseconds with 20-millisecond delay), three episodes in part 2 (CL, 230, 230, and 250 milliseconds with 2-millisecond delay), and one episode each in parts 3 (CL, 260 milliseconds with 2-millisecond delay) and 4 (198 milliseconds with 100-millisecond delay). No episodes of VF were induced for shocks delivered after a CL > 300 milliseconds. CONCLUSIONS: Synchronized transvenous atrial defibrillation shocks delivered on beats with a short preceding ventricular cycle length (< 300 milliseconds) are associated with a significantly increased risk of initiation of VF. To decrease the risk of ventricular proarrhythmia, short CLs should be avoided.
Animals↗
Quantitative cerebrospinal fluid acid-base balance in acute respiratory alkalosis.
Data on canine cisternal cerebrospinal fluid (CSF) ions in acute respiratory alkalosis are limited and fragmentary. We hypothesized that with the fall in arterial PCO2 (PaCO2) and in the face of normal osmoregulation, CSF [Na+] remains relatively constant and CSF [Na+-Cl-] narrows to account in part for the fall in CSF [HCO3-]. We therefore measured blood and CSF acid-base variables and ions of two groups of pentobarbital-anesthetized, mechanically ventilated dogs (n = 10 in each group). In the control group, PaCO2 was kept constant and changes in serum and CSF ions were minimal. In Group II (acute respiratory alkalosis), both PaCO2 and cisternal CSF PCO2 decreased by 10 mm Hg. Five hours after induction of respiratory alkalosis, mean CSF [HCO3-] decreased significantly by 4.4 +/- 1.2 mEq/L (mean +/- SD). The fall in CSF [HCO3-] was similar to changes in CSF strong ion difference (SID = Na(+)+K(+)+Ca(2+)+Mg(2+)-CL(-)-lactate), which decreased 4.4 +/- 1.9 mEq/L. Concentrations of the four major CSF cations did not change significantly. Cisternal CSF lactate rose significantly by 1.2 +/- 0.9 mEq/L, accounting for 25% of the change in CSF [HCO3-]. The remaining (75%) change in CSF [HCO3-] was accounted for by changes in CSF [Cl-].
Acid-Base Equilibrium↗
Stability and activity of intravenous immunoglobulin with neonatal dextrose and total parenteral nutrient solutions.
OBJECTIVE: To determine in vitro the compatibility of reconstituted intravenous immunoglobulin (IVIG) (Gammagard, Baxter-Hyland) with five different neonatal and pediatric intravenous solutions in Viaflex polyvinyl chloride bags. DESIGN: In vitro compatibility study. INTERVENTIONS: Samples were taken at time = 0, 10, 30, 60, 90, and 120 minutes and at 4, 8, 12, and 24 hours and assayed for total immunoglobulin G content and antibodies to hepatitis B surface antigen. Type III group B Streptococcus (GBS) and opsonic activity for type III GBS were analyzed at time = 0, 60, and 120 minutes and 12 and 24 hours. All results were compared with those from pure IVIG. RESULTS: Our results demonstrate that mixing IVIG with intravenous solutions commonly used in the care of premature infants (dextrose 5% in water [D5W], D15W, D5W/NaCl 0.225%, and total parenteral nutrition [TPN]) does not significantly alter total immunoglobulin G concentrations or concentration of antibodies to hepatitis B surface antigen or type III GBS. As well, the in vitro functional activity for type III GBS of the IVIG, when mixed with these solutions for up to 24 hours, remained intact. An apparent decrease in bactericidal killing was seen with the IVIG/central TPN mixture. This apparent decrease was found to be an artifact of the high concentration of glucose (20 percent) in the solution. CONCLUSIONS: We propose that Gammagard may be mixed with these solutions through Y-site connections without loss of antibody content or functional activity of the IVIG.
Antibodies, Bacterial↗
The midcycle gonadotropin surge in normal women occurs in the face of an unchanging gonadotropin-releasing hormone pulse frequency.
The midcycle gonadotropin surge is a critical event in normal reproductive cycles and requires functional integration of the hypothalamus, pituitary, and ovary. To determine whether a change in GnRH frequency occurs coincident with the onset or termination of the surge in normal women, 20 studies were performed at a sampling interval of every 5 min for up to 36 h. The frequency of pulsatile GnRH secretion was assessed by the use of two surrogate markers of its secretion, LH and free alpha-subunit (FAS). The timing of the studies was prospectively determined by serial ultrasound and previous cycle history, whereas measurements of LH, FSH, estradiol, and progesterone in daily blood samples were used retrospectively to locate the frequent sampling study in relation to the day of ovulation in each individual. The frequent sampling studies were divided into late follicular phase (LFP; days -4 to -2) and early, mid-, and late portions of the midcycle surge (days -1 to 1) in relation to the 95% confidence limits of the LH peak derived from daily samples in 69 normal ovulatory women. The patterns of LH and FAS secretion were pulsatile at all times during the midcycle surge. The amplitude of LH pulsations increased from the LFP and early surge to the midportion of the midcycle surge (5.9 +/- 6 and 15.1 +/- 5 vs. 39.0 +/- 3 IU/L; P < 0.0001) and decreased from the mid- to the late portion of the surge (13.4 +/- 5 IU/L; P < 0.0001). Likewise, the amplitude of FAS pulse increased from the LFP and early surge to the midportion of the surge (82.4 +/- 59 and 153.1 +/- 50 vs. 421.4 +/- 35 ng/L; P < 0.0001) and decreased from the mid- to the late portion of the surge (190.8 +/- 49 ng/L; P < 0.0002). Although there was excellent concordance of pulsatile secretion of LH and FAS, significantly more pulses of FAS were detected than of LH (P < 0.0001). There was no change in frequency (expressed as interpulse interval) between the LFP and the early and midportions of the surge for LH (70.0 +/- 8, 67.5 +/- 7, and 65 +/- 5 min, respectively) or FAS (55.1 +/- 7, 54.6 +/- 6, and 60.0 +/- 4 min). However, there was an increase in LH interpulse interval (decrease in pulse frequency) in the late portion of the surge (87.0 +/- 6 min) compared to the early and midportions of the surge (P < 0.02 and P < 0.0005, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Moloney virus induction of T-cell lymphomas in a plasmacytomagenic strain of E mu-v-abl transgenic mice.
Although the v-abl gene can provoke several types of lymphoid neoplasm, mice of a transgenic strain (E mu-v-abl 40) in which lymphocytes are targeted for expression of v-abl by a linked immunoglobulin enhancer (E mu) spontaneously develop only plasmacytomas. To determine whether other lymphocytes of this strain were susceptible to transformation, and to identify genes that can collaborate with v-abl in tumorigenesis, E mu-v-abl 40 mice were subjected to insertional mutagenesis by neonatal infection with Moloney murine leukemia virus. Tumorigenesis was accelerated moderately, but nearly all the tumors were T lymphomas. The altered tumor type may reflect both the T-cell tropism of Moloney virus and the higher level of E mu-v-abl 40 expression found in T lymphocytes than in B lymphocytes. Insertion near the c-myc, N-myc or pim-I gene was observed in 42% of the induced tumors, indicating that each of these genes may collaborate with v-abl in lymphomagenesis. Most of the accelerated tumors had a surprisingly low level of transgene expression. Thus, high expression of v-abl may not be required for Moloney-induced T lymphomagenesis.
Animals↗
Megakaryocytic differentiation induced in 416B myeloid cells by GATA-2 and GATA-3 transgenes or 5-azacytidine is tightly coupled to GATA-1 expression.
The GATA 'zinc-finger' transcription factors are thought to have important roles in the control of hematopoiesis. GATA-1 and GATA-2 are found in the erythroid, mast cell, and megakaryocytic lineages, and GATA-3 in T lymphocytes. GATA-1 is required for erythroid development and has recently been shown by gene transfer to direct megakaryocytic differentiation of the primitive myeloid cell line 416B. Here we show that enforced expression in 416B cells of either the GATA-2 or GATA-3 gene also induces megakaryocytic differentiation, as assessed by cellular morphology, acetylcholinesterase activity, polyploid DNA content, and loss of Mac-1 expression. No erythroid or mast cell differentiation was found. Unexpectedly, the level of endogenous GATA-1 mRNA had increased 20- to 30-fold among the transfectants, whereas that of GATA-2 mRNA was unaltered and endogenous GATA-3 transcripts remained undetectable. This finding suggests that GATA-2 and GATA-3 lie upstream of GATA-1 in a regulatory hierarchy and that, in 416B cells, GATA-1 may mediate the phenotypic changes induced by GATA-2 or GATA-3. Furthermore, 416B cells treated with the DNA demethylating agent 5-azacytidine underwent megakaryocytic differentiation accompanied by a marked increase in the level of GATA-1 mRNA but not that of GATA-2 or GATA-3. These results strongly implicate GATA factors in megakaryocytic differentiation and suggest that, at least for 416B cells, GATA-1 is a dominant regulator of maturation along this lineage.
Azacitidine↗
Enforced expression of Hlx homeobox gene prompts myeloid cell maturation and altered adherence properties of T cells.
Within the hematopoietic compartment, the murine Hlx homeobox gene is expressed in myeloid cells, most prominently in macrophages and granulocytes, and in immature B-lymphoid cells but not in erythroid, mast, or T-lymphoid cells. The level of Hlx mRNA increased with induced differentiation of the promyelocytic lines WEHI-3B and HL-60. To address its biologic action more directly, Hlx expression vectors were introduced into seven mouse hematopoietic cell lines representing several lineages. Although four lines did not tolerate stable Hlx expression, high-level expression was achieved in the early myeloid line FDC-P1 and in the immature T-cell lines Tikaut and WEHI-707. Overexpression of Hlx in FDC-P1 cells downregulated two markers of myeloid immaturity, Thy-1 and CD34, and also promoted changes in cellular and colony morphology, indicative of limited differentiation. Ectopic Hlx expression in the T-cell lines induced changes in cellular and colony morphology and adhesiveness, concomitant with decreased expression of adhesion molecules ICAM-1 (CD54) and Pgp-1 (CD44) and increased expression of heat-stable antigen. These results implicate Hlx in the control of myeloid maturation and the regulation of lymphoid adhesion processes.
Animals↗