[Intervention in early alcohol problems is of significant effect].
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Adult↗
Biomedical subjects
G Dahl
Publications and source records attributed to G Dahl.
Acute vincristine neurotoxicity in the presence of hereditary motor and sensory neuropathy type I.
Acute vincristine neurotoxicity leading to a severe motor and sensory neuropathy has been noted in patients with hereditary motor and sensory neuropathy type I (HMSN-I). The case of a 2-year-old boy with acute lymphocytic leukemia and HMSN-I is reported, and additional cases from the literature are reviewed. Severe vincristine neurotoxicity in patients with HMSN-I may be secondary to impairment of both slow and- fast axonal transport. Vincristine should be used with caution in patients with a family history of polyneuropathy.
Charcot-Marie-Tooth Disease↗
Formation of hybrid cell-cell channels.
The oocyte cell-cell channel assay was used to demonstrate that connexin-43 is a cell-cell channel-forming protein as previously shown for connexin-32. Expression of connexin-32 in one and connexin-43 in the other oocyte of a pair results in the formation of junctional conductances at rates similar to those observed when only one or the other connexin is expressed in both oocytes of a pair. This suggests that hybrid cell-cell channels form in the oocyte system. Hybrid channels also form when a connexin-43 mRNA-injected oocyte is paired with a noninjected oocyte expressing endogenous connexin. The latter hybrids have properties apparently contributed by both types of hemichannels. Pure connexin-43 channels are not voltage gated, whereas pure oocyte channels are voltage dependent; hybrids of these channels rectify.
Animals↗
[Acetylsalicylic acid and Reye's syndrome--is documentation relevant?].
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Aspirin↗
Structure of a gap junction gene: rat connexin-32.
A genomic clone for the rat liver gap junction protein (connexin-32) was isolated and characterized by restriction enzyme mapping and sequence analysis. While the complete coding sequence is contained within one uninterrupted block, the 5'-untranslated region of the transcript contains a 6.1 kb intron. Both S1 nuclease protection and primer extension assays indicate multiple transcription start sites. Sequences homologous to cAMP response elements are found near the transcription start sites and within the 3'-end of the intron.
Animals↗
Expression of functional cell-cell channels from cloned rat liver gap junction complementary DNA.
An oocyte expression system was used to test the relation between a complementary DNA (cDNA) clone encoding the liver gap junction protein and cell-cell channels. Total liver polyadenylated messenger RNA injected into oocytes induced cell-cell channels between paired oocytes. This induction was blocked by simultaneous injection of antisense RNA transcribed from the gap junction cDNA. Messenger RNA selected by hybridization to the cDNA clone and translated in oocyte pairs yielded a higher junctional conductance than unselected liver messenger RNA. Cell-cell channels between oocytes were also formed when the cloned cDNA was expressed under the control of a heat-shock promoter. A concentration-dependent induction of channels was observed in response to injection with in vitro transcribed gap junction messenger RNA. Thus, the liver gap junction cDNA encodes a protein that is essential for the formation of functional cell-cell channels.
Animals↗
Translation and functional expression of cell-cell channel mRNA in Xenopus oocytes.
mRNA from estrogen-stimulated rat myometrium, a tissue known to upregulate cell-cell channels in response to this hormone, was microinjected into Xenopus laevis oocytes. The oocytes had been freed from covering layers of follicle cells and vitelline to allow direct cell membrane interactions when paired. About 4 hours after the mRNA injection, paired oocytes become electrically coupled. This coupling was due to the presence of typical cell-cell channels characterized by size-limited intercellular tracer flux, the presence of gap junctions at the oocyte-oocyte interface, and the reversible uncoupling that occurred in the presence of carbon dioxide. The induction of new cell-cell channels in the oocyte membrane was observed against a zero background or a low level of endogenous coupling, depending on the maturation stage of the oocytes. The time course of development of cell-cell coupling after the microinjection of mRNA was determined. The mRNA capable of inducing cell-cell coupling was confined to an intermediate size class when fractionated on a sucrose gradient.
Animals↗
Lysophosphatidylcholine increases rat ileal permeability to macromolecules.
The influence of lysophosphatidylcholine (LPC) on macromolecular permeability in the distal ileum has been studied. Using a rat experimental model, we determined the intestinal permeability to different sized dextrans (3000-70 000 daltons) and bovine serum albumin (BSA) in the absence and presence of LPC. We also examined the morphology of the ileal mucosa after deposition of LPC in the gut lumen, and determined N-acetyl-beta-glucosaminidase, 5'-nucleotidase, and alkaline phosphatase activities in suspensions of isolated mucosal cells and different concentrations of LPC. We found that 20 mM LPC damaged the ileal mucosa and that it increased its permeability to all the molecules investigated. Moreover, mixtures of mucosal cells and 0.01-1 mM LPC showed increased N-acetyl-beta-glucosaminidase activity: the higher the LPC concentration, the higher the enzyme activity. These findings indicate that LPC, a naturally occurring surfactant in the intestine, might damage mucosal cells and release lysosomal enzyme activity, and that higher LPC concentrations may impair the mucosal barrier function and increase the gut permeability to macromolecules such as proteins. This could have relevance to the development of various disease states, in which increased intestinal absorption of macromolecules is of importance.
Animals↗
Clinical relevance of lymphoblast biological features in children with acute lymphoblastic leukemia.
Improvements in therapy for childhood acute lymphoblastic leukemia (ALL) have led us to reevaluate the prognostic significance of lymphoblast characteristics at diagnosis. From application of univariate and multivariate statistical methods, we determined the relationship of five blast cell features to treatment outcome in 250 patients who were enrolled in two clinical trials at this center from May 1979 through April 1982. Karyotype ploidy, lymphoblast morphology, and immunophenotype were each significantly related to prognosis as measured by time to failure, while periodic acid-Schiff reactivity and glucocorticoid receptor number lacked prognostic implication for this patient population. In addition, clinical features of initial WBC count, age, and race were also significant independent variables in predicting treatment response. By multivariate analysis, both ploidy and morphology contributed prognostic information to a clinical model based on WBC count, age, and race. If the model was adjusted for impact of ploidy, however, French-American-British morphology no longer contributed additional prognostic information. Our findings suggest that many traditional biological features used to estimate prognosis in ALL can be discarded in favor of clinical features (leukocyte count, age, and race) and cytogenetics (ploidy) for planning of future clinical trials.
Adolescent↗
Transient myeloproliferative syndrome in a phenotypically normal infant.
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Antigens, Surface↗
New chromosomal translocations correlate with specific immunophenotypes of childhood acute lymphoblastic leukemia.
Cytogenetic analysis of leukemic cells obtained at diagnosis from 122 patients with childhood acute lymphoblastic leukemia (ALL) disclosed chromosomal translocations in 36 cases. Two new nonrandom translocations were identified and found to be associated with specific immunophenotypes of the disease. The first, identified in 4 of 16 cases of T-cell ALL positive for sheep erythrocyte receptors (E+), involved the short arm (p) of chromosome 11 and the long arm (q) of chromosome 14 and was designated t(11;14) (p13;q13). The second, found in 7 of 23 cases with a pre-B-cell phenotype, involved the long arm of chromosome 1 and the short arm of chromosome 19; it was designated t(1;19) (q23;p13.3). A third abnormality involving a common breakpoint on chromosome 12 (band p 12) was also identified. These two new differentiation-specific translocations suggest a mechanism for aberrant expression of genes that influence lymphoid cell growth and development, as well as leukemogenesis.
Adolescent↗
Heavy chain immunoglobulin gene rearrangement in acute nonlymphocytic leukemia.
Samples of leukemic cell DNA from 14 children with acute nonlymphocytic leukemia (ANLL) and 4 human myeloid leukemia cell lines were analyzed for rearrangement in the heavy chain region of the immunoglobulin gene. The diagnosis of ANLL was confirmed in all patients by morphological, cytochemical, and immunologic studies. By restriction endonuclease digestion and hybridization with cloned heavy chain immunoglobulin gene probes for the constant (Cmu) and joining (JH) regions, the DNA of 2 patients and 1 cell line (ML-1) was found to contain rearrangements. The DNA from the remaining 12 patients and 3 cell lines was not rearranged (germline configuration). Both patients with apparent immunoglobulin gene rearrangement achieved complete remission on therapy for ANLL. Immunoglobulin gene rearrangement in phenotypically defined ANLL suggests (1) that such changes may not be limited to lymphoid leukemia of B cell lineage, or (2) that, in some patients, the leukemic transforming event may involve stem cells capable of both B cell and myeloid differentiation.
Acute Disease↗
Studies on the biogenesis of cell-cell channels.
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Animals↗
Voltage-dependent activation of potassium current in Helix neurones by endogenous cellular calcium.
1. The effect of endogenous Ca on potential-dependent K current IKD, was examined in identifiable neurones of Helix aspersa. The suction pipette method of internal perfusion was used along with a combined voltage-clamp method in which the membrane potential was measured by a separate glass micro-electrode and the current was passed by the suction pipette. Activation of the potential-dependent A current, IA, was prevented by using holding potentials of -40 mV where IA is inactivated and by the addition of the A-current blocker 4-aminopyridine. Activation of K currents by transmembrane Ca current, IKCa, was suppressed by Co substitution for Ca ion extracellularly. 2. Under these conditions, IKD rose to a peak value and then subsided to a steady level. The current-voltage (I-V) relationship for peak IKD had an upward bump at about +50 mV that gave it an S-shape. The I-V curve for steady IKD rose continuously. Peak and steady IKD were reduced by perfusing with EGTA or F ions intracellularly. The EGTA effect occurred at intracellular Ca activity levels below 10(-7) M. Increases in the concentration of EGTAi at constant Cai had no additional effect; however, recovery experiments do not allow us to rule out some direct action of EGTA on IKD. 3. Prolonged extracellular perfusion with Co-substituted solutions also reduced IKD and the effects occurred more quickly when the solutions were made hypertonic or caffeine was added to them. The peak transient was abolished, and the small remaining steady IKD (about 5-10% of normal peak IKD) was blocked by tetraethylammonium. IKD could be restored by the temporary reintroduction of Ca in the extracellular solution. 4. The S-shape of the peak I-V relationship for IKD may be due to Ca released from an endogenous site by membrane depolarization. The reduction of steady and peak IKD to very low values by Ca chelators or prolonged perfusion with Ca-free solutions indicates that Cai is important for activation of these K channels. 5. Three cellular structures were identified in electron micrographs of freeze-fractured neurones that could be involved in potential-dependent endogenous Ca release. These were a restricted extracellularly space, an intracellular membrane system of endoplasmic reticulum that may be fused to the internal face of the plasma membrane (the subsurface cisterns of Henkart & Nelson, 1979), and intracellular vesicles that also may be fused to the plasma membrane.
Animals↗
Intermittent maintenance therapy in chronic hand eczema with clobetasol propionate and flupredniden acetate.
The clinical effect of two topical corticosteroids, one of very strong potency (clobetasol propionate), and one of medium potency (flupredniden acetate), was studied in the maintenance therapy of 55 patients with chronic hand eczema. Initially, 61 patients were treated on both hands continuously for 1 to 3 weeks with clobetasol only which brought about healing in 90% of cases (mean time to healing: 11 days). In a subsequent double-blind left/right study, the capacity of the two corticosteroids for keeping the dermatitis in remission was compared using an intermittent schedule of 2 applications a week. The protocol was followed by 46 patients and the mean observation period was 138 days. Treatment with clobetasol kept patients free from relapses during the entire observation period in 70%, with flupredniden in 30%. Relapses occurred with clobetasol after a mean of 66 days, with flupredniden after 36 days. Side-effects, occurring with similar frequency with both drugs, were few and mild. It is suggested that an intermittent schedule is advantageous when using a corticosteroid of high potency.
Betamethasone↗
Partial Turner's syndrome in four girls with Xq duplication and Xp deficiency.
Four girls with some clinical symptoms of Turner's syndrome had Xq duplication and Xp deficiency, their karyotypes being 46,X,dup(X)(p113;q11), 46,X,dup(X)(p212;q211), 46,X,dup(X)(p225;q13), and 46,X,dup(X)(p222;q213). No mosaicism was found. The major clinical findings, short stature, lack of pterygium colli, and no continuous gamete production, are compared with those in three previously published cases.
Adolescent↗
Hormonal regulation of cell junction permeability: upregulation by catecholamine and prostaglandin E1.
By cellular activation with hormones, we test the proposition (Loewenstein, W.R., Physiol. Rev. 61:829, 1981) that the permeability of cell junction is upregulated through elevation of the level of cyclic AMP. Cultured rat glioma C-6 cells, with beta-adrenergic receptors, and human lung WI-38 cells, with prostaglandin receptors, were exposed to catecholamine (isoproterenol) and prostaglandin E1, respectively, while their junctions were probed with microinjected fluorescent-labelled mono-, di-, and triglutamate. Junctional permeability, as indexed by the proportion of cell interfaces transferring the probes, rose after the hormones treatments. The increase in permeability took several hours to develop and was associated with an increase in the number of gap-junctional membrane with an increase in the number of gap-junctional membrane particles (freeze-fracture electron microscopy). Such interaction between hormonal and junctional intercellular communication may provide a mechanism for physiological regulation of junctional communication and (perhaps as part of that) for physiological coordination of responses of cells in organ and tissues to hormones.
Alprostadil↗
The prevalence of chromosome abnormalities among mentally retarded persons in a geographically delimited area of Denmark.
A cytogenetic survey of an unselected group of mentally retarded persons in a geographically limited area was made in order to establish the frequency of chromosome abnormalities within this group. In the area there were 2,157 patients, both institutionalized and living at home. A chromosome analysis was performed in 1905 cases; 359 (18.8%) of these had a chromosome anomaly: 281 (14.7%) Down's syndrome, 45 (2.4%) autosomal anomaly other than Down's, and 33 (1.8%) sex chromosome anomaly. The frequency of chromosome aberrations in relation to the whole group was higher compared with similar surveys, which leads to the conclusion that the total number of mentally retarded persons living within a limited area is determined by many factors. This means that a comparison between frequencies of abnormal chromosomes in an unselected group of mentally retarded persons is only relevant when related to the whole population living in the investigation area.
Chromosome Aberrations↗