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Biomedical subjects

A Forster

Publications and source records attributed to A Forster.

At least 163 records · Page 9Linked to original sources

Respiratory response to histamine- and methylcholine-induced bronchospasm in nonsmokers and asymptomatic smokers.

The respiratory response to bronchospasms of the same magnitude induced by inhalation of histamine or methylcholine was measured non-invasively, using bellow pneumographs, in nonsmokers and asymptomatic smokers. In each subject, tidal volume (VT), breathing frequency (f) and inspiratory time (TI) were obtained on two different days, in a randomized crossover fashion, with the following sequence: basal conditions, after inhalation of buffered saline as a control and after histamine or methylcholine inhalation. Basal and control conditions did not differ from each other and were the same for both groups. The respiratory responses to both bronchoconstrictors did not differ from each other and were also the same in both groups: VT increased, f and TI remained unchanged. Thus, VT/TI, an index of respiratory drive, also increased. In nonsmokers the increased VT/TI and the associated increase in minute ventilation were both correlated to the decrease in FEV1. These correlations were not found in smokers. Although they have different effects on airway irritant receptors, inhaled histamine and methylcholine induce the same respiratory response in nonsmokers and smokers. Thus, the presumed smoking-related changes in airway mucosa permeability do not seem to influence the direct stimulating effect of histamine on these endings. The absence of correlation between FEV1 and VT/TI changes in smokers suggest that smoking might affect the respiratory drive in acute drug-induced bronchospasm.

Administration, Inhalation↗

The mechanism of chromosome 14 inversion in a human T cell lymphoma.

The chromosome 14 inversion produces cytogenetic breakpoints at either end of the long arm of this chromosome. Previous studies have shown that a hybrid gene (designated IgT) consisting of an immunoglobulin VH gene segment and T cell receptor J alpha C alpha segments encompasses the telomeric breakpoint in SUP-T1, a cell line derived from a human T cell lymphoma. Here, we report that the centromeric breakpoint in SUP-T1 constitutes the reciprocal of a VH-J alpha join but involves gene segments different from those at the telomeric breakpoint. Therefore, chromosome inversion and IgT formation were mediated by two sequential VH-J alpha joining events. Moreover, sequences adjacent to the centromeric breakpoint detect a T-cell-specific RNA, encoded within the immunoglobulin VH locus, whose transcriptional activity may have facilitated the illegitimate VH-J alpha rearrangements.

Chromosome Inversion↗

Epstein-Barr virus-transformed human precursor B cell lines: altered growth phenotype of lines with germ-line or rearranged but nonexpressed heavy chain genes.

A series of lymphoblastoid cell lines (LCLs) have been established by in vitro infection of fetal bone marrow and fetal liver cells with Epstein-Barr virus (EBV). While most lines showed the usual mature B cell phenotype, a small proportion were cytoplasmic and surface immunoglobulin (Ig) heavy and light chain negative. Analysis of gene rearrangements indicated that the Ig- lines were either germ-line or nonproductively rearranged when probed for JH and were in germ-line configuration for C chi; no mu or chi mRNA could be detected in such cells. Precursor B cell lines were indistinguishable from their normal Ig+ counterparts in their expression of a wide variety of cell surface markers including "activation" antigens usually associated with the lymphoblastoid state; even the single LCL showing germ-line heavy and light chain genes expressed B lineage-specific cell surface antigens. However, the Ig- lines were distinct from their Ig+ counterparts in three important respects: (a) they grew much more slowly and achieved lower saturation densities, (b) they showed unusually high proportions (8-16%) of cells in EBV-productive cycle, and (c) they contained unusually high proportions (up to 40%) of cells expressing free joining (J) chain. These results suggest that precursor B cells differ in their response to the growth-transforming effects of EBV such that the virus-cell interaction in precursor B cell lines is inherently less stable than in conventional LCL. In particular there may be a greater movement of cells out of cycle and along the B cell maturation pathway. It is possible that such movement leads in individual cells either to virus replication or to a "sterile" plasmacytoid differentiation with J chain expression in the absence of Ig synthesis.

Antibody Formation↗

Unusual forms of T cell gamma mRNA in a human T cell leukemia cell line: implications for gamma gene expression.

The expression and rearrangement of T cell rearranging (TRG) gamma genes in human leukemic cell lines has been examined. The cell line MOLT-17 produces abundant gamma mRNA which is translated into a protein found on the cell surface which is associated with the CD3 molecule. The analysis of the gamma mRNA sequences in MOLT-17, by cDNA cloning, shows transcripts of aberrantly rearranged genes as well as the productively rearranged allele. The productive allele consists of a rearranged V gamma 8 gene joined to J gamma 2. Two forms of aberrant transcript originate from the other rearranged gamma allele. One of these initiates just upstream of the unrearranged J gamma 2 segment, and the other initiates from a V gamma 8 gene segment joined to another J gamma segment, upstream of J gamma 2. An unusual feature of the latter transcript is that polyadenlyation has occurred at the end of the first exon of C gamma 2, where two conserved poly(A) addition signals occur. The MOLT-4 cell line, on the other hand, has productively and nonproductively rearranged gamma alleles, from which relatively little transcription occurs. These results define new J gamma segments in the human TRG gamma locus and suggest that positive activation of the gamma locus is necessary for high level transcription after rearrangement.

Amino Acid Sequence↗

New subgroups in the human T cell rearranging V gamma gene locus.

Two new V gamma genes in humans are described from rearrangement in T cell lines, which constitute single members of new V gene subgroups of the T-cell rearranging gamma (TRG gamma) locus. These two genes (herein designated as belonging to V gamma III and V gamma IV subgroups) are located between V gamma I/V gamma II subgroups and the constant (C) gamma genes. The existence of these new genes brings the number of different, potentially useable, human TRG V gamma genes to eight (excluding at least five pseudo V gamma genes) and the number of distinct subgroups to four. Polymorphism in the sequence of the V gamma II subgroup gene is also described and rearranged fragment sizes which make possible an unequivocal assignment of a V gamma rearrangement are given. These results extend previous conclusions of the inherited diversity of the human TRG V gamma locus.

Amino Acid Sequence↗

Dynamic splinting following flexor tendon repair.

Electromyographic investigation of subjects wearing dynamic flexor tendon repair (Kleinert) splints shows a wide variability in the amount of contraction in the flexor digitorum profundus muscle during extension of the finger. We suggest there is no advantage in giving extra resistance to the extensor muscles, and that the strength of the rubber bands needs to be only just sufficient to flex the finger passively back to its resting position.

Adult↗

[Assessment of the efficacy and tolerance of a benzodiazepine antagonist (Ro 15-1788)].

The aim of this study was to evaluate the efficacy and the tolerance of Ro 15-1788, a specific benzodiazepine antagonist, in reversing the effects of midazolam. Six healthy male volunteers (mean age 32 +/- 3 years; mean weight 75.5 +/- 5 kg) took part in this study. Two of the three following drugs: midazolam (0.15 mg X kg-1), Ro 15-1788 (0.1 mg X kg-1) or placebo, diluted in 10 ml isotonic saline, were injected intravenously in 15 s at 5 min intervals in a double-blind manner in each subject during six randomized sessions: midazolam-placebo; Ro-placebo; placebo-midazolam; placebo-Ro; midazolam-Ro; Ro-midazolam. At least four days were allowed between each session for each subject. The evaluation of the effects on the central nervous system was as follows. At the time of injection of the first drug and, if possible, at the time of injection of the second drug, the subject was asked to count aloud to 150. The following variables were timed: start of dysarthria, cessation of counting, abolition and duration of absence of the ciliary reflex and duration of induced sleep. Retrograde and anterograde amnesia were evaluated by the recall of a playing card and a number. Haemodynamic effects (variations of systolic and diastolic pressures and pulses rate) as well as respiratory ones (apnoea) were also studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Alpha, beta and gamma T-cell receptor genes: rearrangements correlate with haematological phenotype in T cell leukaemias.

We have studied the arrangement of the alpha, beta and gamma T cell receptor (TCR) genes in 27 patients with T cell lymphoproliferative disorders. Nine patients had acute lymphoblastic leukaemia (T-ALL), nine patients had prolymphocytic leukaemia (PLL), six patients presented with a T-CLL/T-lymphocytosis syndrome, two patients had Sezary syndrome (SS) and one patient had HTLV-I positive T-cell leukaemia/lymphoma (ATLL). alpha TCR gene rearrangement could be demonstrated by the use of three available probes in only one case. By contrast, both beta and gamma TCR gene rearrangement could be demonstrated by Southern blot analysis of DNA samples digested with appropriate restriction enzymes in the majority of cases. In general, when rearrangements were present they involved both alleles. The proportion of rearranged chromosomes was lower in T-ALL than in other forms of T-cell leukaemia and it was lower in cases with the CD4-/CD8+ phenotype than in those with a CD4+/CD8- phenotype. In three out of 34 cases of B-cell leukaemia the TCR beta-gene but not the TCR gamma-gene was rearranged, just as in two out of 26 cases of T-cell leukaemia the immunoglobulin (Ig) heavy chain but not the light chain genes were rearranged. These data suggest that development of the machinery required for gene rearrangement may precede commitment to B or T cell lineage. The use of this technique is especially useful for the classification of cases of ALL in which the cells are negative with respect to most current phenotypic markers and in cases of T cell lymphocytosis in which the finding of a gene rearrangement identifies a monoclonal cell population.

Adolescent↗

Effects of a specific benzodiazepine antagonist (RO 15-1788) on cerebral blood flow.

RO 15-1788, a specific benzodiazepine antagonist, although it effectively antagonizes the clinical effects of benzodiazepines (i.e., sedation and amnesia), can also induce subjective agonist effects such as sedation or inverse agonist effects such as anxiety. The purpose of this study was to investigate in seven healthy volunteers the effect of RO 15-1788 on cerebral blood flow when intravenously injected alone or with midazolam and to compare its effects with midazolam administered alone. Cerebral blood flow was measured with the 133xenon inhalation technique and the drugs were administered simultaneously in a double-blind, randomized fashion during the four following sessions: placebo-placebo; midazolam-placebo; RO 15-1788-placebo; midazolam-RO 15-1788. No difference in cerebral blood flow was noted between the placebo-placebo, the RO 15-1788-placebo, and the RO 15-1788-midazolam sessions--although midazolam injected alone decreased cerebral blood flow by 30%. The sedation, amnesia, and the electroencephalograph (EEG) and muscle tone changes observed with midazolam-placebo were not present during the RO 15-1788-placebo and RO 15-1788-midazolam sessions. This study demonstrates the absence of effects of RO 15-1788 on cerebral blood flow when injected alone and the efficacy of this new drug in antagonizing the depressant effects of midazolam on cerebral hemodynamics.

Adult↗

Diversity and rearrangement of the human T cell rearranging gamma genes: nine germ-line variable genes belonging to two subgroups.

We describe nine T cell gamma variable (V) gene segments isolated from human DNA. These genes, which fall into two subgroups, are mapped in two DNA regions covering 54 kb and probably represent the majority of human V gamma genes. One subgroup (V gamma I) contains eight genes, consisting of four active genes and four pseudogenes. The single V gamma II gene is potentially active. Sequence analysis of the V gamma I genes shows variation clustered in hypervariable regions, but somatic variability is restricted to N-region diversity. Studies on rearrangement in T cell lines and in thymic DNA show that major rearrangements can be observed that are attributable to the five active V gamma genes. In addition, human cells with the phenotype of helper T cells can undergo productive V gamma-J gamma joining.

Bacteriophage lambda↗

Genetic polymorphism and exon changes of the constant regions of the human T-cell rearranging gene gamma.

The genomic nucleotide sequences of the constant-region (C) genes of the human T-cell rearranging gene gamma are given. These sequences show considerable allelic and nonallelic variation. Allelic variants exist at both C gamma 1 and C gamma 2 loci in coding regions (as well as in restriction enzyme sites). Both C gamma genes are in the same transcriptional orientation. Moreover, the organization of the nonallelic C gamma genes reveals some interesting features: the C gamma 1 gene, like the mouse C gamma gene, has three exons, whereas the C gamma 2 gene has four exons, including a duplicated second exon that would create a putative protein with an enlarged constant region. However, these two duplicated exons in C gamma 2 have lost the cysteine residue that is thought to be involved in the interchain disulfide bridge.

Alleles↗

Clinical evaluation of a specific benzodiazepine antagonist (RO 15-1788). Studies in elderly patients after regional anaesthesia under benzodiazepine sedation.

The efficacy, usefulness and side effects of RO 15-1788 (RO), a specific benzodiazepine (BZD) antagonist, have been evaluated. Sixty-two patients (ASA I-III, mean age 72 +/- 9 yr) scheduled for urological surgery under regional anaesthesia and BZD sedation received placebo or RO in a randomized, double-blind fashion at the end of the procedure, following sedation with midazolam. When compared with placebo, RO improved alertness and collaboration for 15 min, and suppressed anterograde amnesia for 60 min. No major side effect was noted, although five patients became anxious after administration of RO. Two cases of a paradoxical reaction to midazolam were treated successfully by RO.

Aged↗

Noninvasive evaluation of breathing pattern and thoraco-abdominal motion following the infusion of ketamine or droperidol in humans.

The authors compared the respiratory effects of an intravenous infusion of ketamine (1 mg X kg-1) with droperidol (0.1 mg X kg-1), or placebo on three different occasions in a double-blind, randomized fashion in eight healthy volunteers. Breathing pattern, thoraco-abdominal motion, end-expiratory positions of the rib cage and abdomen, arterial hemoglobin oxygen saturation (SaO2), and end-tidal carbon dioxide concentration (FECO2) were continuously measured with noninvasive techniques. During the 1-h monitoring period following drug injection, droperidol produced occasionally significant but clinically unimportant differences in respiratory variables when compared with placebo. In contrast, ketamine induced a significant (P less than 0.001) and persistent increase in minute ventilation (+75%) from 5 to 20 min after start of infusion by increasing both the driving (i.e., tidal volume/inspiratory time [VT/Ti]) and the timing (i.e., inspiratory time/total respiratory cycle time [Ti/Ttot]) components of ventilation (Milic-Emili J, Grunstein MM: Chest 70 (Suppl): 131-133, 1976). This was obtained without any significant change in end-expiratory positions or change in relative rib cage contribution to tidal volume. Despite multiple apneic episodes observed with ketamine, the subjects maintained a stable SaO2 and FECO2, indicating no resting respiratory depression. This study, performed with a noninvasive respiratory monitoring technique, confirms that droperidol infused over 5 min at a clinically used dosage does not cause respiratory depression in healthy subjects, whereas ketamine produces an important ventilatory stimulation.

Abdomen↗

Multiple complications after internal jugular vein catheterisation.

We report a case of a young female who developed multiple life threatening complications after a single internal jugular vein catheterisation. They consisted of pleural misplacement of the catheter, massive haemorrhage with cardiovascular collapse following catheter removal, and development of arteriovenous fistula, diagnosed 18 months later.

Adolescent↗