As to the clastogenic-, sister-chromatid exchange inducing-and cytotoxic activity of inosine triphosphate in cultures of human peripheral lymphocytes.

The influence of commercial inosine triphosphate (ITP) on the chromosome aberration rate, the mitotic rate, sister-chromatid exchange (SCE) frequency, and the proportion of first (X1), second (X2) and third (X3) division metaphases was investigated in 72h cultures of human peripheral lymphocytes. The blood donors had mild inactive arthrosis and a normal health check-up. All cultures of each volunteer were set-up simultaneously. In contrast to a previous report [Arch. Biochem. Biophys. 278 (1990) 238-244], it was demonstrated in two preliminary studies (number of subjects, n=5 each) that ITP at a final concentration of 100 microM does not induce chromosomal aberrations and, furthermore, that not ITP concentrations higher than 100 microM but ITP doses higher than 3.8mM prohibit culture growth. Based on these results, cultures with a final ITP concentration of 3.6mM (max.) and 1.8mM (max./2) were compared with control cultures (number of subjects n=10; three males and seven females, mean age x=57.6 years). Whereas no increase in the chromosomal breakage rate was observed in cultures with an ITP concentration of 1.8mM and only a marginally significant one (P=0.048) for 3.6mM ITP cultures, a highly significant induction of SCEs, not only at an ITP concentration of 3.6mM (P<0.0001) but also at 1.8mM (P<0.0001) was seen. The increase in the SCE frequency was not linear, but steeper from 0 to 1.8mM than from 1.8 to 3.6mM. Nevertheless, the difference between 1.8 and 3.6mM cultures was significant (P=0.027). The distribution of the number of SCEs per metaphase as well as the distribution of SCEs per chromosome correspond to the expected Poisson values. The investigation of the cytotoxic effect of the studied ITP concentrations revealed a highly significant reduction of the mitotic rate from 0 to 1.8mM as well as from 1.8 to 3.6mM in the aberration studies (all P values are equal to smallest possible one for a sample size of 10, namely, 0.002), and in the SCE studies there is a significant decrease in the X3 frequency when ITP is increased (0-1.8mM: P=0.0061 and 1.8-3.6mM: P<0.0001). The proportion of X1 within all X1 and X2 metaphases changes significantly only at the second dose step (0-1.8mM ITP: P=0.22 and 1.8-3.6mM ITP: P<0.0001). The results are discussed.

Case report: sicca syndrome due to primary amyloidosis.

Sicca syndrome consists of two major clinical findings: keratoconjunctivitis sicca and xerostomia due to destruction of the lacrimal and salivary gland parenchyma. Although it is most often due to Sjögren's syndrome, a variety of other diseases causes sicca syndrome. We report the rare case of a patient with gland infiltration in primary amyloidosis. Sonographic, computed tomographic and magnetic resonance findings are presented.

Hypoplasia of the corpus callosum and growth hormone deficiency in the XXXXY syndrome.

A 3-year-old Libyan boy with the XXXXY syndrome is described. MRI examination of the brain showed hypoplasia of the corpus callosum. He had growth retardation and endocrine studies demonstrated growth hormone (GH) deficiency. Dermatoglyphic pattern was different from previous reports. At histological examination of the undescended testes, Leydig cells were seen although they are usually not found in this variant of the Klinefelter syndrome.

Cytogenetic and dermatoglyphic findings in a familial case of hypomelanosis of Ito (incontinentia pigmenti achromians).

Cytogenetic and dermatoglyphic investigations were performed in a mother (M.B.) and her daughter (D.B.), who were both suffering from hypomelanosis of Ito (incontinentia pigmenti achromians; HI). Whereas quite normal chromosomal results could be obtained after culture of peripheral lymphocytes, a diploid/tetraploid mosaicism (46,XX/92,XXXX) was found in cultured skin-fibroblasts derived from a hypopigmented skin area of M.B., with a slowly decreasing tetraploidy rate in the course of passaging: #2 23%, #5 11%, #11 and #14 6% and #18 and #21 2%. In cultures of normally pigmented skin, only single tetraploid cells could be detected. Dermatoglyphic examinations in both patients showed single transverse creases, a high number of secondary creases and a longitudinal alignment of the main line A bilaterally, and there was a tricentric fingertip pattern on the right digit III of M.B., i.e. a pattern which occurs very seldom in human beings. The results are discussed in respect to the clinical-diagnostic overlap of HI and incontinentia pigmenti Bloch-Sulzberger.

Age-related influence of piracetam on mitotic index and number of silver-stained nucleolus organizer regions.

Mitotic indices and the number of silver-positive nucleolus organizer regions (AgNORs) were scored in phytohemagglutinin-stimulated cultures of peripheral lymphocytes from two age groups of females (mean = 23.1 and 84.0 yr, respectively) under the influence of Piracetam (2-oxo-pyrrolidine-1-acetamid; Nootropil, Reg. No. 17051) and in simultaneously set up control cultures without Piracetam addition. Piracetam concentrations of 10, 14 and 16 mg/ml culture medium produced a highly significant, decreasing effect on both parameters tested, without an age-related difference. Lower Piracetam concentrations (2 and 4 mg/ml culture medium) showed a depressant effect on some of the cultures only; but, on average, there was a rather equal, significant, dose-dependent, linear decrease of the mitotic indices of both age groups, whereas the suppressive effect on the number of AgNORs was significant in cultures from the young females only.

[Molecular biology in diagnosis and detection of deletion in Duchenne muscular dystrophy]. / Molekularbiologische Diagnostik und Deletionsnachweis bei Duchennescher Muskeldystrophie.

For the purpose of carrier identification and genetic counselling we investigated deletions of the Duchenne muscular dystrophy (DMD) gene in three families of patients with Duchenne muscular dystrophy. Using a limited number of probes of the DMD cDNA in Southern blots, we detected a deletion in only one patient. Additional methodology is necessary to warrant reliable identification of carriers and exact prenatal diagnosis.

[Gene technology from the viewpoint of genetic counseling]. / Gentechnologie aus der Sicht genetischer Beratung.

Gentechnology detects genetic defects at the DNA level. Direct analysis, which may be performed without family investigations, is the most reliable and therefore the most desirable means of detection. Indirect analysis on the other hand-using restriction fragment length polymorphisms (RFLP) - requires family investigations and the pedigrees are not always informative; furthermore, meiotic recombination may occur leading to erroneous conclusions. Pre-symptomatic diagnosis of a severe disease may cause serious psychical and ethical problems. Prenatal diagnosis by gentechnology may be made after amniocentesis or chorionic villi sampling.

Dermatoglyphics and creases in patients with neurofibromatosis von Recklinghausen.

Fingerprint and palmar dermatoglyphics and creases were investigated in 60 patients (20 males and 40 females) with generalized neurofibromatosis. Like previous investigators, we found a significantly increased frequency of digital central pocket patterns. Furthermore, affected males and females had an increased frequency of monocentric whorls (P = 0.0037), higher quantitative values on digit II of both hands (P = 0.04), more often a reduction of main line C (P less than 0.05) with decreased frequencies of patterns in the 3rd and 4th interdigital area of the left hand (P less than 0.05), and a lower ab ridge count (males P less than 0.005; females P less than 0.001) than control individuals. On the right hand of males the frequency of high endings (5' or 5'') of line A was decreased (P less than 0.05). A significantly increased frequency of Sfl (Sydney line) was found in female patients (P less than 0.001). Male and female patients often showed a high number of secondary creases (P less than 0.001).

Central pockets in dermatoglyphic analysis: classification, frequency, twin and family data.

Central pockets were defined as small, loop-enclosed whorls whose quantitative values must not exceed the third part of the quantitative value of the loop or as small, whorl-like patterns in the core of a loop having at least one curved ridge with its convexity towards the opening of the loop. Applying this classification scheme, the frequency of central pockets was found to be 17.5% in 200 males and 17.0% in 200 females, but was significantly higher in a sample of 21 male and 22 female pairs of MZ twins (33.2% and 34.1%, respectively). Twin as well as family data (94 families with 269 children) pointed to a rather weak hereditary influence upon the formation of central pockets. Rudimentary central pockets occurred in 9.5% of males and 10.0% of females. Since no common genetic basis could be established for central pockets and rudimentary central pockets, the latter should not be scored as central pockets.

[Determination of average fiber density (single fiber lead), quantitative electromyography and serum CK in the detection of Duchenne carriers]. / Bestimmung der mittleren Faserdichte (Einzelfaserableitung), der quantitativen Elektromyographie und der Serum-CK zur Erfassung von Duchenne-Trägern.

The fibre density of the extensor digitorum communis muscle was examined with a monopolar single fiber electrode in 2 definite, one probable and 15 possible Duchenne-carriers. In addition serum-CK was evaluated three times in intervals of a least one week. The fibre density was increased in one definite, one probable and 4 possible carriers (greater than 1.6). The highest value was 2.0. Excepting one case the increase of fibre density was accompanied by an increase of serum-CK (greater than 60 mg%). The highest value of CK was 1626 mg%. The conventional EMG was pathological in 2 cases. In no case with an increase of CK or with pathological EMG the fibre density was normal. The fibre density is an unspecific but rather sensible indicator of Duchenne-carriers but as we could observe in a definite carrier, negative results do not exclude carriers.

Effect of donor age on inter- and intrachromosomal distribution of sister chromatid exchanges in cultured human lymphocytes.

The distribution of sister chromatid exchange (SCE) points has been analyzed in cultured lymphocytes from three age-groups of 30 females (n = 10; young: 13-20, middle-aged: 30-55, old: 75-84 years). The observed interchromosomal SCE distribution is in good agreement with the results of previous workers, significant age-dependent differences could not be established. It has only to be mentioned that chromosome E16 showed a relative SCE deficiency in young females, a result which has to be affirmed by further studies. Analysis of intrachromosomal SCE distribution revealed a surplus in the midarm section of most chromatid arms. Besides very similar distribution patterns in all three age-groups, there were some, mostly insignificant differences which had to be verified by further investigation.

[Multiple sclerosis and chromosomal aberrations (author's transl)]. / Chromosomenuntersuchungen bei multipler Sklerose.

Chromosomal investigations were performed after peripheral lymphocytes taken from 25 healthy females and from 35 female patients suffering from various types of multiple sclerosis had been cultured for 48 hours. The incidence of cells with chromosomal breaks in multiple sclerosis patients (2.0%) was significantly higher than in controls (1.1%): Chi2 = 7.26; DF = 1; p less than 0.01. Furthermore, chromosomal rearrangements (dicentric chromosomes, translocation chromosomes, chromatid exchange figures) were observed more frequently in the MS patients than in the controls. Analysis of the interchromosomal distribution of breaks found in the patients revealed a relative surplus in chromosome A2 and D-group chromosomes.

Dermatoglyphics and systemic lupus erythematosus.

Finger tip and palmar dermatoglyphics of 37 female patients with systemic lupus erythematosus (SLE) were compared to 100 female controls; patients and controls were native inhabitants of the Eastern part of Austria. SLE patients had a significantly higher frequency of low endings of line A on both hands, and-on the left hand-significantly more patterns in the fourth and fewer patterns in the third interdigitum. There was no association between these dermatoglyphic features and the HLA antigens (B8 an DRw3), which occurred most frequently in our SLE patients.

"Benign" monoclonal IgE gammopathy.

So far IgE monoclonal paraproteins have been found only in patients with malignant diseases, though there are benign monoclonal paraproteins of other immunoglobulin classes. A patient with osteoporosis first seen in Paris in 1965 was found to have a paraprotein type lambda. In 1977 immunoelectrophoresis identified this as IgE lambda paraprotein, and immunodiffusion studies showed precipitin bands identical with those in patients with IgE myeloma. This patient seemed to have a benign monoclonal IgE gammopathy which had existed for 14 years. Though the possibility of transition into multiple myeloma cannot be excluded, this case suggests that a monoclonal expansion of IgE lymphocytes need not produce malignant change.

Reduction of main line C.

Fifteen hundred palmar prints of normal persons and patients suffering from various diseases were studied and classified as to dermal ridge configurations at the base of digit IV, after the exclusion of main line C courses with endings at one of the palmar marginal regions. This classification scheme, based on the three classical reduction forms of line C (O,X(8),x), resulted in the differentiation of three main groups, A, B, and C. Within these main groups, pattern types with strong similarity were combined to subgroups allowing an easier documentation. Twin and family data were used to test whether the described pattern types, besides the classical abortive states O,X and x of line C (called special and intermediate forms), are heritable and for which of them a remarkable reduction tendency could be established. The results allow us to confirm the main grouping and the assumed reduction tendency of the special forms of group A.