Biomedical subjects
J Philip
Publications and source records attributed to J Philip.
"White forelock"-an embarassing curiosity.
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Automatic chromosome analysis. II. Karyotyping of banded human chromosomes using band transition sequences.
Human chromosomes, represented by band transition sequences, chromosome area, centromeric index by area and centromeric index by density, were karyotyped by computer. A reference set of chromosomes provided frequencies of occurrence of each density class and difference class of the band transition sequence as well as of each of the three global features. The karyotyping program was designed to handle all metaphases, even those from which severely bent and overlapped chromosomes were excluded. In one experiment, 21 metaphases were karyotyped on the basis of a reference set and the results were compared with earlier results of visual analysis of band transition profiles developed from band transition sequences: 0.8% errors were made in the visual experiment and 1.4% errors were made in the computer based experiment. In a second experiment, 179 metaphases were divided into reference and test sets and karyotyped by computer with an error rate of 3.4%. By further analysis it was found that metaphases with many misclassified chromosomes could often be automatically distinguished from metaphases with few errors. Thus by automatic rejection of 7% of the metaphases the error rate could be reduced to 2.6%. The computer program for chromosome karyotyping will now be implemented in a semi-automatic system for practical clinical chromosome analysis.
Work load produced by breast-cancer screening.
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[Premenstrual syndrome, drug advertising and sex discrimination].
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Identification and analysis of persistent contaminants associated with gemcadiol.
Application of several analytical probes indicated that certain batches of the investigational new drug gemcadiol (2,2,9,9-tetramethyl-1,10-decanediol) were contaminated with impurities whose nature and source were unknown. Subsequent study showed that these impurities consisted of polymeric material formed by self-condensation of the dialdehyde precursor. Gel permeation chromatographic techniques were found to be useful in the analysis of polymers present in both the aldehyde precursor and the finished drug.
Citrullinaemia: the possibility of prenatal diagnosis.
Argininosuccinate synthetase activity in amniotic fluid cells from a fetus at risk for citrullinaemia was low compared to the activity in amniotic fluid cells from a normal fetus, but five times the activity in fibroblasts from a patient with citrullinaemia. These enzyme values indicated indicated a normal or heterozygous fetus. Chromosome analysis of the amniotic fluid cells from the fetus at risk, however, showed an unusual X/20 translocation. As we could not guarantee the delivery of a normal child, the parents chose to have a therapeutic abortion. Argininosuccinate synthetase activity in the liver and kidney of the aborted fetus was in the normal and heterozygous range respectively, confirming the prenatal diagnosis. The activity in the father's fibroblasts was low, less than 10% of normal. The difficulty of interpreting the results of prenatal diagnosis in such a family and the importance of studying parental cells are discussed.
Concanavalin A reactivity pattern of human amniotic fluid AFP examined by crossed affino-immunoelectrophoresis. A definite test for neural tube defect?
The percentage of alpha-fetoprotein (AFP) not reacting with concanavalin A (con A) was determined by crossed line affino-immunoelectrophoresis in amniotic fluid from 25 pregnancies with neural tube defects (NTD) and other fetal abnormalities giving rise to elevated AFP levels, and from 128 pregnancies with normal outcome. The percentage of con A non-reactive AFP is significantly lower in the presence of fetal abnormalities (mean 3.4%, range: 0.0-6.3, n = 25), compared to the percentage found in normal pregnancies (mean 17.2%, range: 6.6-35.8%, n = 128). In amniotic fluid samples from normal pregnancies, the percentage of con A non-reactive AFP in 84 cases with total AFP levels lying within the 95% reference interval was not significantly different from the percentage found in 44 cases with levels above the 95% reference interval. The percentage of non-reactive AFP in fetal serum and cerebrospinal fluid was of the same magnitude as found in amniotic fluids of pregnancies with fetal abnormalities. It is concluded that analysis of the percentage of con A non-reactive AFP by crossed line affino-immunoelectrophoresis is a simple, reliable and apparently diagnostic test for NTD and other abnormalities with leakage of fetal serum or cerebrospinal fluid into the amniotic fluid. The test should therefore be used in all cases with only marginally elevated AFP levels, so false positives may be avoided.
Quantitative analysis of 6985 digitized trypsin G-banded human metaphase chromosomes.
The frequency and staining intensity of the dark bands were measured in 6985 trypsin G-banded human chromosomes, described by so-called band transition sequences which represent the chromosome banding patterns in a condensed quantitative way. In the haploid chromosome complement a maximum of 351 bands were registered: 181 white and 170 dark bands. The frequency with which bands occurred and the staining intensity of the bands differed considerably between the chromosome types. Among the dark bands the darker stained bands occurred more frequently than the lighter stained bands. A study of the relationship between the degree of chromosome contraction and the frequency of band occurrence revealed that for all chromosome types the average band frequency increased with increasing chromosome elongation. Twenty of the 23 dark bands chosen as landmarks by the Paris Conference (1971) occurred with high frequency and staining intensity. The remaining three landmarks occurred less frequently, due to fusion of dark and white bands, respectively. A study of global features showed, as expected, good agreement between chromosome length, area and density. there was good agreement between the centromeric indices determined by length and area, respectively, and no difference was found between contracted and elongated chromosomes, with the exception of the acrocentrics where elongated chromosomes showed higher centromeric indices than contracted chromosomes. Most often, the centromeric index by density differed considerably from the centromeric indices by length and area, respectively. The data presented here may be used in clinical cytogenetics as a supplement to the ISCN idiograms (ISCN 1978), as the band frequencies and staining intensities may help in identifying and characterizing specific bands.
Clinical trial with levo-norgestrel and testosterone oenanthate for male fertility control.
Two groups of six men took levo-norgestrel (250 or 500 microgram daily) by mouth and testosterone oenanthate (200 mg monthly, intramuscurlarly) for six months. A three months placebo period preceded the medication which was followed by a recovery phase of 6-10 months. Two volunteers withdrew due to side effects. The five men taking the low doses of levo-norgestrel (250 microgram) exhibited a reduction in sperm count, but not to azoospermia. The high dose of levo-norgestrel (500 microgram) was more effective, sperm count was reduced to < 6 X 10(6)/ml in 3 of 5 volunteers and to < 17 X 10(6)/ml in the remainder. s-Testosterone, LH and FSH were decreased by the treatment. The men had no toxicological side effects or changes in libido and potency. During the recovery period sperm counts, sperm morphology, s-testosterone, LH and FSH returned to normal levels.
Monozygotic twins with dissimilar phenotypes and chromosome complements.
A case history of monozygotic twins is presented. Twin A showed gonadal dysgenesis and chromosomal mosaicism (45,X0/46,XX). Twin B was a phenotypical normal female with the karyotype 46,XX. Fifteen previous reports of monozygotic twins with gonadal dysgenesis are reviewed. Dissimilar phenotypes seem to be the rule rather than the exception, and mosaicism is found in the majority of cases with dissimilar phenotype. The assumption is made that the chromosome disorder leading to gonadal dysgenesis arises postzygotically, eigher before or after the process leading to twinning.
Automatic chromosome analysis. I. A simple method for classification of B- and D-group chromosomes represented by band transition sequences.
This paper describes an approach to the automatic analysis of banded B- and D-group chromosomes, represented by band transition sequences (BT-sequences), using Bayes formula in a simple way. The analysis considers the 14 BT-codes constituting the BT-sequence as being independent variables. Error rates of 6-8% in classification experiments and 3-4% in karyotyping experiments are clearly smaller than those reported by other authors using other methods. If the error rates of karyotyping are adjusted for errors in the basic material, they are reduced to 2-3%. The reason for the small error rate is presumably that the BT-sequences are superior to other methods for condensed band-pattern description. The method will be incorporated into a programme system for automatic karyotyping.
[Prenatal diagnosis of hemophilia].
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[Severe combined immunodeficiency. Successful bone marrow transplantation from father to child].
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[3,000 examinations of amniotic fluid in a year].
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The effects of low doses of cyproterone acetate on some functions of the reproductive system in normal men.
One daily dose of either 5 mg or 10 mg cyproterone acetate (CA) was administered to 2 groups of 4 fertile men for 6 months. The medication was preceded by a 3 months placebo period and followed by a recovery phase of 5 to 8 months. During CA-treatment the sperm count/ml decreased and the percentage of abnormal spermatozoa increased slightly (0.991 less than P less than 0.05). Sperm penetration assessed by the Kremer test did not show any decrease during treatment. Serum levels of testosterone and FSH decreased, but those of LH remained unchanged during treatment. Two pregnancies occurred after 13/4 and 51/2 months of CA-treatment. The serum-CA concentration in these 2 volonteers did not differ from that of the remainder. Three subjects who began the study were withdrawn because of depressive mood changes (2) and weakness combined with dizziness (1). Data from these subjects were not included. The results indicate that daily doses of 5 mg and 10 mg of cyproterone acetate are not effective as a male contraceptive.
[Ambulatory legal abortion].
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Outcome of pregnancy after amniocentesis for chromosome analysis.
A consecutive series of 1177 pregnant women examined by amniocentesis for chromosomal abnormalities delivered 1039 live-born babies weighing over 2500 g and 79 live-born babies weighing under 2500 g. Twenty-six abortions were induced (2.2%)--13 (1.1%) because of chromosomal abnormalities--and 28 women (2.4%) aborted spontaneously; in these cases chromosomes were normal. Analysis of all spontaneous abortions in the series suggested that 0.3-0.7% might have resulted from amniocentesis.