The psychosomatic theory of bronchial asthma.

The author discusses the development of the psychosomatic asthma theory as a paradigm of theory formation in psychomatic medicine. The first formulation of the theory was based on clinical and psychiatric observations. It was tested by psychological, physiological and experimental methods and as a result was reformulated and extended. In its present form it regards asthmatic breathing as a reaction of a predisposed personality structure (partly hereditary, partly acquired during a youth situation in which overprotection by a domineering parent played a large role), to an ambivalent conflict with a key figure. The resulting frustration is not acted out by aggressive, flight, or depressive behaviour, but inhibited; thereby the motoric and verbal discharges are displaced into (substituted by) a respiratory behaviour pattern, which is characterised by an abnormally forceful contraction of the abdominal muscles during the expiration. The resulting high intraabdominal pressure is transmitted into the thorax where it pushes the posterior membranaceous wall of the trachea and large bronchi forward into the lumen and thus produces a long stretched obstruction of the large airways. The passage of the air through the compressed large air passages under high pressure and low velocity is the mechanism which causes the typical wheeze and the other manifestations of the asthmatic airway obstruction. A hypothesis is suggested for the ways in which this psychoneurogenic respiratory behaviour contributes to the so-called bronchial hyper-reactivity and the secondary development of allergies.     

In vivo autofluorescence imaging of early cancers in the human tracheobronchial tree with a spectrally optimized system

The changes in the autofluorescence characteristics of the bronchial tissue is of crucial interest as a cancer diagnostic tool. Evidence exists that this native fluorescence or autofluorescence of bronchial tissues changes when they turn dysplastic and to carcinoma in situ. There is good agreement that the lesions display a decrease of autofluorescence in the green region of the spectrum under illumination with violet-light, and a relative increase in the red region of the spectrum is often reported. Imaging devices rely on this principle to detect early cancerous lesions in the bronchi. Based on a spectroscopic study, an industrial imaging prototype is developed to detect early cancerous lesions in collaboration with the firm Richard Wolf Endoskope GmbH, Germany. A preliminary clinical trial involving 20 patients with this spectrally optimized system shows that the autofluorescence can help to detect most lesions that would otherwise have remained invisible to an experienced endoscopist under white light illumination. A systematic off line analysis of the autofluorescence images pointed out that real-time decisional functions can be defined to reduce the number of false positive results. Using this method, a positive predictive value (PPV) of 75% is reached using autofluorescence only. Moreover, a PPV of 100% is obtained, when combining the white light (WL) mode and the autofluorescence (AF) mode, at the applied conditions. Furthermore, the sensitivity is estimated to be twice higher in the AF mode than in WL mode.     

Effects of Behavioral Control and Type A Behavior on Cardiovascular Responses

The purpose of this study was twofold: (a) to examine the relationship between degree of behavioral control and cardiovascular changes in 60 adult males performing an anagram solution task, and (b) to assess the interaction between behavioral control and type of subject (A vs. B). Three conditions were used, differing from each other in the percentage of solvable anagrams (100, 50, and 30%). Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured before, during, and after the anagram task. In all conditions, during-task SBP, DBP, and HR were significantly elevated above baseline. Blood pressure (BP) elevations appeared to be curvilinearly related to degree of behavioral control, i.e., more elevated in the 50% than in the 100% and 30% conditions. HR changes did not differ among conditions. Concerning the Type A behavior pattern, the results revealed significantly greater BP elevations for Type A than for Type B subjects, especially in the 50% condition, thereby confirming that the physiologic correlates of Type A behavior are predominantly evoked in challenging circumstances. Findings were discussed in the light of results of cardiovascular and endocrinological research. Consideration was given to the possible role of disengagement in the 30% condition and to differences in the pattern of responding between As and Bs.     

Clinical evidence of the nonpathogenic nature of the M34T variant in the connexin 26 gene

Mutations in GJB2 are the most common cause of congenital nonsyndromic hearing loss. The controversial allele variant M34T has been hypothesized to cause autosomal dominant or recessive nonsyndromic hearing impairment and some in vitro data has been consistent with this hypothesis. In this report, we present the clinical and genotypic study of 11 families (seven familial forms of nonsyndromic sensorineural hearing loss (NSSNHL) and four sporadic cases) in which the M34T GJB2 variant has been identified. The M34T mutation did not segregate with the deafness in six of the seven familial forms of NSSNH. Eight persons with normal audiogram presented a heterozygous M34T variation and five normal hearing individuals were composite heterozygous for M34T and another GJB2 mutation. Four normal hearing individuals with a documented audiogram were M34T/35delG and one was M34T/(GJB6-D13S1830)del. Screening a French control population of 116 subjects we have found an M34T allele frequency of 1.72%. This percentage was not significatively different from the prevalence of the M34T allele in the deaf population, which was 2.12%. All these data suggest that the M34T variant is not clinically significant in human and is a frequent polymorphism in France.     

Biologic activity of guinea pig IFN-gamma in vitro.

Interferon-gamma (IFN-gamma) plays a key role in the induction and maintenance of immunity against intracellular infectious agents. Compared to other species, little is known about the biology of this cytokine in the guinea pig (Cavia porcellus). We found that in contrast to humans and mice, IFN-gamma in the guinea pig did not induce the antiviral state, which in other species leads to protection of IFN-gamma -stimulated fibroblasts from the cytopathic effect (CPE) of subsequent viral infections. As an alternative strategy to detect and quantify guinea pig IFN-gamma activity in vitro, a reporter system using guinea pig fibroblasts transfected with a luciferase gene, which is regulated by an IFN-stimulated response element (ISRE), was established. With the help of the highly sensitive reporter assay system, the biologic activity of recombinant guinea pig IFN-gamma (GpIFN-gamma, from prokaryotic and eukaryotic expression systems was detected. The response to both native and recombinant GpIFN-gamma was inhibited by a rabbit antiserum directed against the recombinant cytokine expressed in Escherichia coli, demonstrating structural and functional homology of native and recombinant GpIFN-gamma. Stimulation with GpIFN-gamma, obtained from transfected cells, induced upregulation of MHC class I expression in a guinea pig fibroblast line. The restricted activity of GpIFN-gamma might have implications for this species' ability to control infections with intracellular pathogens.     

Genetic and physical characterization of the early-onset Alzheimer's disease AD3 locus on chromosome 14q24.3

Genetic linkage studies have provided significant evidence thata major gene defect, AD3, for familial early-onset Alzheimer'sdisease (EOAD) is located at chromosome 14q24.3, between theshort tandem repeat (STR) markers D14S52 and D14S53 defininga genetic size of 22.7 cM for the AD3 candidate region. We constructeda physical map of the AD3 region using yeast artificial chromosomes(YACs) selected from both the CEPH and megaCEPH YAC librariesusing the AD3 linked STR markers as well as new sequence-taggedsites (STSs) designed based on YAC terminal sequences. The YACmap is contiguous in the region between D14S258 and D14S53,a region of 8.2 cM, and has an estimated physical size of 4–8Mb. The YAC contig map was used as a framework to localize threeknown genes, a pseudogene and two brain expressed sequence tags(ESTs). Linkage analysis studies in two Belgian chromosome 14EOAD families AD/A and AD/B, identified obligate recombinantsin family AD/A with D14S289 and D14S61 reducing the geneticsize of the candidate AD3 region substantially. The minimalAD3 candidate region measured 6.4 cM on the genetic map andis contained within six overlapping megaCEPH YACs that covereda physical distance estimated between 2 and 6 Mb. These YACsas well as other YACs in the YAC contig map are valuable resourcesin gene cloning efforts or genomic sequencing experiments aimingat isolating the AD3 gene.     

Our experience with diagnostics of congenital disorders of glycosylation

The aim of this study is to report our 3years experience with the screening of congenital disorders of glycosylation. A common isoelectric focusing method with immunofixation was used for analysis of serum transferrin and alpha1-antitrypsin, apart from several other procedures. A group of about 1000 individuals, both healthy controls and patients, mostly with signs of a metabolic disease were examined. Here we present an overview of (1) hypoglycosylation findings, (2) distribution of protein variants, (3) misguiding rare Tf variants found in our set, and (4) association of some phenotypes with various diseases.     

Chromosomal radiosensitivity of breast cancer with a CHEK2 mutation

Recently, multiple studies have shown that a sequence variant in CHEK2 (CHEK2 1100delC) plays a role in the susceptibility to breast cancer. This mutation should confer about a twofold increased breast cancer risk in women and a 10-fold increased risk in men. Because the CHEK2 gene plays a critical role in DNA damage repair and the CHEK2 1100delC variant confers susceptibility to breast cancer, we investigated if patients carrying the CHEK2 1100delC mutation are characterized by an enhanced chromosomal radiosensitivity. To this end, familial breast cancer patients, sporadic breast cancer patients, and healthy women, considered in our previously studied to determine their chromosomal radiosensitivity with the G2 and G0-MN assay, were all tested in present study for the presence of the CHEK2 1100delC variant. The 1100delC variant was detected in none of the 100 healthy individuals, in 1 of 100 (1%) unselected breast cancer patients and in 3 of 78 (3.8%) breast cancer patients with a family history of breast cancer. The breast cancer patients with the CHEK2 1100delC genotype had a mean radiation-induced yield of chromatid breaks that was not significantly different from that of the healthy control group. Although the mean yield of micronuclei (MN) was significantly higher compared to the healthy control group, this higher mean MN yield was due to a single patient who had a very high number of MN compared to the parallel control. Our data suggest that breast cancer patients with a CHEK2 1100delC mutation are in general not characterized by a distinct enhanced chromosomal radiosensitivity. These conclusions are, however, very preliminary, because of the small numbers of CHEK2 1100delC breast cancer patients studied.     

The origin of the extrinsic adrenergic innervation to the rat ovary

Cutting the suspensory ligament reduced the ovarian content of norepinephrine (NE) to less than half that of controls and only a few blood vessels had perivascular fibers and an occasional nerve remained in the interstitial gland. Cutting the ovarian plexus had a less drastic, but similar effect on the ovarian content of NE and on the pattern of ovarian adrenergic nerves. Cutting both the suspensory ligament and ovarian plexus eliminated visualization of ovarian adrenergic nerves, but some ovarian NE was still measurable. Fluorescence and electron microscopic studies of the suspensory liagament revealed a large adrenergic nerve embedded in smooth muscle of the ligament. The nerve was also acetylcholinesterase-positive. Cutting the celiac plexus or incising a small nerve lateral to the plexus and medial to the origin of the suspensory ligament, had the same effect on the ovarian adrenergic nerves as cutting the suspensory ligament. It is concluded that the extrinsic adrenergic nerves to the rat ovary reach the organ by two routes: one via the nerve in the suspensory ligament (superior ovarian nerve), and one via the traditionally described ovarian plexus along the ovarian artery.