bluuebunny/crossref_metadata_2025 huggingface dataset:
Cleft palate: A genetic and epidemiologic investigation
Authors: Shields Edward D. , Bixler David , Fogh‐Andersen Poul
Published: July 2010

An examination of kindred histories of 561 Danish probands who have non‐syndromic CP has indicated that neither a multifactorial‐threshold model nor a single major locus model is completely compatible with the data. This suggests etiologic heterogeneity for CP, which was tested with kindred data.

As recommended by Smith (1976), an attempt to define partially this heterogeneity within the CP phenotype was undertaken by grouping and comparing the kindred data. It is both reasonable and heuristic to propose that CP, as defined in this investigation, is composed of three groups: (1) Syndromic CP; (2) Familial CP, which appears to have an autosomal dominant component to its etiology, and (3) Non‐familial CP which, by demonstrating an increasing frequency of CP and a maternal age effect, appears to be related to environmental factors which may cause CP or other malformations.
Dominant inheritance of microcephaly with short stature
Authors: Burton Barbara K.
Published: July 2010

A family is reported in which microcephaly has been observed in at least three generations. The pedigree is most consistent with autosomal dominant inheritance. In addition to microcephaly, affected individuals exhibit significantly short stature, ocular anomalies and simple, protruding ears. Intellectual function is in the normal or borderline range.
Gonadal dysgenesis, intra‐X chromosome insertion, and possible position effect in an otherwise normal female
Authors: Grass Frank S. , Schwartz Robert P. , Deal Jane O. , Jr James C. Parke
Published: July 2010

A 16‐year‐old female was referred for cytogenetic evaluation because of primary amenorrhea. Growth, mental development, and physical examination, including secondary sexual characteristics, were normal. Cytogenetic analysis revealed one X chromosome to be consistently more metacentric than the other. Measurements indicated no significant differences between the two X's, but in the abnormal X, the increase in length of the short arm matched the decrease in length of the long arm. Banding studies suggest that region q22 through q24 of the abnormal X is inserted into region p11 of the same chromosome. Endocrine studies were indicative of gonadal dysgenesis. Since no loss of X chromosome material is involved, this patient's gonadal dysgenesis is most likely related to position effect.
An Indian family with postaxial Polydactyly in four generations
Authors: Kucheria Kiran , Kenue R. K. , Taneja Neelam
Published: July 2010

An Indian family was observed with postaxial Polydactyly in four generations. Of the twelve affected cases, eleven were male and one was female. The affected males showed postaxial Polydactyly Type A in both hands and feet. The affected female showed poly‐syndactyly and both Types A and B postaxial Polydactyly. Study of this family strongly suggests a common causal factor for postaxial Polydactyly Types A and B and polysyndactyly. The observations also support an autosomal dominant pattern of inheritance and a high degree of genetic heterogeneity in this malformation.
Sanfilippo syndrome type C: assay for acetyl‐CoA: α‐glucosaminide N‐acetyltransferase in leukocytes for detection of homozygous and heterozygous individuals
Authors: Klein Udo , Kamp Jacques J. P. van de , Figura Kurt von , Pohlmann Regina
Published: July 2010

An assay for the detection in leukocytes of homozygous and heterozygous carriers of Sanfilippo syndrome type C is described. In one family with two patients suffering from Sanfilippo C syndrome, the affected individuals had no residual activity of acetyl‐CoA: α‐glucosaminide N‐acetyltransferase. The determination of the acetyl‐CoA: α‐glucosaminide N‐acetyltransferase/β‐glucuronidase ratio allows the discrimination between obligate heterozy‐gotes and normal individuals and may be used for carrier detection.
Urinary amino acids and organic acids in the Sjögren‐Larsson syndrome
Authors: Holmgren G. , Jagell S. , Seeman H. , Steen G.
Published: July 2010

A metabolic study of urine samples obtained from 35 patients with the Sjögren‐Larsson syndrome (SLS) has been performed by means of a series of chemical tests, as well as by analysis of the amino acid pattern by high‐voltage paper electrophoresis. Organic acids were analysed by gas‐chromatography‐mass spectrometry and qualitative analyses for mono‐and disaccharides were performed by thin‐layer chromatography on cellulose. No error in the amino acid, organic acid or carbohydrate metabolism was found in the SLS‐patients in the present study.
Glycogen storage disease: long‐term follow‐up of nocturnal intragastric feeding
Authors: Michels Virginia V. , Beaudet Arthur L. , Potts V. Elaine , Montandon Corinne M.
Published: July 2010

Nocturnal intragastric feeding of patients with certain hepatic forms of glycogen storage disease has been advocated as an effective treatment, resulting in improved blood chemical values and linear growth. We are reporting the long‐term follow‐up of five patients with glycogen storage disease; three with type Ia, one with type Ib, and one with type III disease. All had improvement in one or more of the following: linear growth, serum glutamic oxaloacetate transaminase, total lipids, cholesterol, phospholipids, or triglycerides. None had significant improvement in venous CO2, serum lactate or urate. One of the patients in this study died after 1.1 years of treatment, and another patient developed hepatocellular carcinoma after 4.4 years of treatment. Nocturnal intragastric feeding, in conjunction with appropriate daytime feeding, is helpful in the management of patients with glycogen storage disease but response to treatment is variable, and it remains to be determined whether the ultimate prognosis of the diseases can be improved.
Treatment of phenylketonuria during pregnancy
Authors: Michels Virginia V. , Justice Cynthia L.
Published: July 2010

A woman with apparently classic phenylketonuria (PKU) was treated from the sixth week of her pregnancy with a diet restricted in phenylalanine and supplemented with tyrosine. Serum phenylalanine levels were monitored weekly and documented good patient compliance. A female infant was born who was examined at age 8.5 months. Physical examination was notable for a heart murmur suggestive of patent ductus arteriosus. Developmental quotient was normal. It is important to continue to monitor the outcome of pregnancies in women with PKU whose diet is restricted in phenylalanine in an effort to better define risks and to optimize treatment.
Structural anomalies of the X chromosome: personal observation and review of non‐mosaic cases
Authors: Wyss Danielle , DeLozier Celia D. , Daniell James , Engel Eric
Published: July 2010

We describe a new case of partial deletion of the long arm of the X chromosome, found in a 24‐year‐old female with secondary amenorrhea; the karyotype of the proposita is 46, X, del(X)(q22). We take this opportunity to review the previously published descriptions of non‐mosaic structural anomalies of the X chromosome (X isochromosomes excepted), with the goal of “testing” the recent hypotheses formulated about: (a) the existence of an X inactivation center (Therman et al. 1974b); (b) the presence of a “b” segment remaining active on Xp (Therman et al. 1976); (c) the potential importance of a critical area on Xq linked to gonadal function (Sarto et al. 1973); and (d) the presence of normal gonadal function despite an Xp terminal deletion (Fraccaro et al. 1977). We conclude that the above‐mentioned theories, as well as those concerning phylogenetic evolution of sex chromosome morphology presented by Lyon (1974) and Hoo (1975), receive support from practically all of the 149 cases we compared. Regarding the features of the Turner syndrome, we propose “mapping” of the X chromosome as follows: the genes involved in gonadal function seem to be located on the proximal part of Xp and on the distal part of Xq, whereas the genes whose absence is responsible for somatic features of the syndrome may be distributed along the length of Xp and the middle section of Xq(q21‐q26). Furthermore, we note some interesting analogies between the evolutionary model proposed by Hoo (1975) and the map we visualize.
Mucolipidosis II: unusual presentation with a congenital angulated fracture
Authors: Michels Virginia V. , Dutton Robert V. , Caskey C. Thomas
Published: July 2010

A newborn infant who was subsequently shown to have mucolipidosis II was noted to have a congenital angulated fracture. The appearance of the fracture led to an original clinical impression of osteogenesis imperfecta. Although pathologic fractures are frequently evident by roentgenographic examination, to our knowledge this is the first report of a congenital angulated fracture in a patient with mucolipidosis II.
Mosaic tetrasomy 21 in a liveborn male infant
Authors: Hunter Alasdair G. W. , Clifford Brian , Speevak Marsha , MacMurray S. Brock
Published: July 2010

A male infant with several clinical signs of Down syndrome, but with additional features not usually seen in that syndrome, was found to have a 47, XY, t(21;21) karyotype in all skin fibroblasts examined. The same karyotype occurred with very low frequency and together with a normal cell line in blood lymphocytes. We have been unable to find reports of a similar case.
Heterogeneity of insulin‐dependent diabetes–new evidence
Authors: Dunsworth T. S. , Rich S. S. , Morton N. E. , Barbosa J.
Published: July 2010

We have performed complex segregation and linkage analysis in 182 families with at least one insulin‐dependent diabetic proband. All families were typed for B histocompatibility (HLA) antigens and 118 for DR. The recessive model fit the data best, with maximum likelihood estimates of recombination between HLA DR and the susceptibility factor of 0.019. Substantial heterogeneity was suggested, with smallest estimated recombination for pedigrees whose probands have two high‐risk DR alleles. The results are compatible with a strong, tightly HLA‐linked susceptibility factor and evidence for additional non‐HLA linked genetic factor(s).
Fetal dermatoglyphics
Authors: Katznelson M. Bat‐Miriam , Goldman B.
Published: July 2010

Dermatoglyphic studies were performed on 24 aborted human embryos in whom major chromosomal aberrations had been revealed by amniocentesis. Prints were obtained from the embryos by the Hollister method. An analysis was done using patterns on finger tips and the atd angle was measured in degrees. The Penrose classification was used to describe the locations of the various palm and foot patterns. Twenty‐two out of the 24 embryos showed dermatoglyphic deviations that correlated well with the cytogenetic diagnosis. The fetuses had the following disorders: 7 with trisomy 21, 2 with trisomy 18, 2 with trisomy 13, 3 with structural autosomal aberrations and 10 had a sex‐chromosome aberration.
Ichthyosis in the Sjögren‐Larsson syndrome
Authors: Jagell S. , Lidén S.
Published: July 2010

The Sjögren‐Larsson syndrome (SLS) is characterized by congenital ichthyosis, spastic dior tetraplegia and mental retardation. The inheritance is autosomal recessive. All 36 patients with SLS alive in Sweden in 1980 were studied with regard to ichthyosis. A slight or moderate generalized hyperkeratosis, less pronounced in the face, was already present at birth. Collodion‐like membranes were never seen. The ichthyosis developed to its full extent during infancy. It was sometimes slight but most often moderate. Three types of hyperkeratosis were observed: dandruff‐like, lamellar and non‐scaly. These types occurred in various combinations. The skin changes were concentrated in the neck, flexures and lower abdomen, in which regions the scales were often dark. The non‐scaly hyperkeratosis produced characteristic and easily visible skin markings. Generalized erythema was rare, especially in adults. The DNA synthesis of the epidermis and the production of a horny layer were increased. Hair and nails were normal, as also was the ability to sweat.
Metachromatic leukodystrophy caused by a partial cerebroside sulfatase defect
Authors: Kihara Hayato , Fluharty Arvan L. , O'Brien John S. , Fish Charles H.
Published: July 2010

A patient with neuropathy and myopathy since infancy but whose neuropathy had been stable for a number of years showed a profound deficiency of arylsulfatase A in leukocytes and urine. Urine contained material that stained metachromatically and cochromatographed with cerebroside sulfate. In contrast, cultured fibroblasts contained about 10–20 % of normal arylsulfatase A with properties identical to properties of normal fibroblast enzyme, except that it showed no cerebroside sulfatase activity. Growing fibroblasts in the cerebroside sulfate loading test had an attenuated rate of sulfatide hydrolysis. A reexamination of the cerebroside sulfatase reaction revealed that while only limited hydrolysis occurred with low concentrations of taurodeoxycholate or chelate (type I activation), significant hydrolysis of the natural substrate did take place with high concentrations of cholate (type II activation). This suggests that there is a partial cerebroside sulfatase defect in this atypical form of metachromatic leukodystrophy.
Pure XX gonadal dysgenesis in identical twins
Authors: Youlton Ronald , Michelsen Harold , Be Cecilia , Cruz‐Coke Ricardo
Published: July 2010

Pure gonadal dysgenesis has been described in several sibships. We report a pair of monozygous twins and their younger sister with secondary amenorrhea. They had no associated congenital anomalies. Plasma FSH levels were elevated and the ovarian biopsies showed absence of follicular structures. Their karyotypes were 46XX, further supporting the concept that this form of familial gonadal dysgenesis is an autosomal recessive defect.
A familial pericentric inversion of chromosome 8 analysed with a high resolution chromosome banding technique
Authors: Bui The‐Hung , Sichong Zhang , Castro Isabel
Published: July 2010

A familial pericentric inversion of chromosome 8 is described. The break points were localized by a high resolution chromosome banding technique and found to be inv(8)(p23.108q12.100). None of the family members had an unbalanced product of the inversion. There were no phenotypical abnormalities in the carriers. The break points and segregation pattern are compared with those of previously reported pericentric inversions of chromosome 8.
A boy with proximal trisomy 15 and a male foetus with distal trisomy 15 due to a familial 13p;15q translocation
Authors: Annerén Göran , Gustavson Karl‐Henrik
Published: July 2010

A familial 13p;lSq translocation was ascertained through a mentally retarded boy with a proximal trisomy 15 syndrome. His mother, who was a balanced 13p;15q carrier, had in addition a legal abortion after 22 weeks of gestation because of a prenatal diagnosis of distal trisomy 15 in a male foetus. Her mother and two sisters, who were balanced carriers, all had children with either a normal karyotype or a balanced translocation or had had pregnancies resulting in an early spontaneous abortion.
Catechol‐O‐methyltransferase activity in erythrocytes in Down's syndrome: family studies
Authors: Gustavson Karl‐Henrik , Flodérus Ylva , Jagell Sten , Wetterberg Lennart , Ross Svante B.
Published: July 2010

Catechol‐O‐methyltransferase (COMT) activity in erythrocytes was measured in six children with Down's syndrome and in their parents to determine if COMT activity is related to a gene on chromosome 21. A gene dosage effect was a possible explanation of the COMT value in three of the children but not in the other three.
Adrenoleukodystrophy: diagnosis and carrier detection by determination of long‐chain fatty acids in cultured fibroblasts
Authors: Tönshoff Burkhard , Lehnert Willy , Ropers Hans‐Hilger
Published: July 2010

In cultured fibroblasts of adrenoleukodystrophy (ALD) patients and most heterozygotes, concentrations of long‐chain fatty acids (> C22) were significantly higher than in controls when cells were assayed 45 days after reaching confluence. Intermediate values were found in three independent cultures of a girl with manifest ALD, suggesting that a significant proportion of her fibroblasts does not express the defect. Though long‐chain fatty acid concentrations in heterozygotes were somewhat higher than expected, suggesting a slight preponderance of defective cells, it may be too early to conclude that somatic selection is a consistent finding in cultured fibroblasts of ALD carriers.
Elucidation of an unbalanced chromosome translocation by gene dosage studies
Authors: Sandison A. , Broadhead D. M. , Bain A. D.
Published: July 2010

A chromosome abnormality, 46, XY, lp +, was detected in cultured amniotic fluid cells. The chromosomes of both parents were normal and it was impossible to recognise the extra chromosomal material using current banding techniques. The activity of acid a‐glucosidase was found to be consistently higher than controls whereas activity of several other lysosomal enzymes, galactokinase and thymidine kinase was not. The results suggest that the extra material is that part of the long arm of chromosome 17 bearing the gene for acid a‐glucosidase but not the genes for galactokinase and thymidine kinase. This would narrow the assignment of the acid α‐glucosidase locus to 17q2 2–17qter.
A case of retinoblastoma, associated with histiocytosis‐X and mosaicism of a deleted D‐group chromosome (13q14→q31)
Authors: Orye E. , Benoit Y. , Coppieters R. , Jeannin Ph. , Vercruysse C. , Delaey J. , Delbeke M.‐J.
Published: July 2010

A previously unpublished association of retinoblastoma and histiocytosis‐X is described in a girl. In addition, chromosome analysis revealed a mosaicism of normal and abnormal mitoses. A deleted D‐group chromosome (13q14‐q31) was present.
A syndrome of short stature, joint laxity and developmental delay
Authors: Anderson Carol E. , Bocian Maureen E. , Walker Ann P. , Lachman Ralph , Rimon David L.
Published: July 2010

Two unrelated patients are described with congenital short‐limbed dwarfism, lax joints, occasional dislocations, and developmental delay (especially in language). Although these patients have some features of the Larsen syndrome, they appear to be distinct and resemble one previously reported sporadic patient, also thought to be distinct from Larsen syndrome.
A total population study of diagnosed chromosome abnormalities in Queens land, Australia
Authors: Bell J. , Pearn J. , McCarthy C. , Jones L. , Trouton C. , Hunt F. , Berry L.
Published: July 2010

Aneuploidy and structural chromosome rearrangements comprise a significant group of abnormalities in the general population. The true incidence of such abnormalities can be obtained by large research studies of consecutive newborns. In practice, the observed incidence of such chromosome abnormalities is obtained by karyotyping subjects who present for clinical reasons. The difference between the observed clinically indicated rates and the assumed rate (by comparison with data from consecutive newborn studies) would allow the estimation of the unrecognised chromosome abnormality load in the general population. The difference between these two rates would provide valuable data concerning the appropriateness of selection techniques for routine chromosome analysis. This paper reports such a study, from Queensland, Australia. A total population 5‐year survey (1976–1980) of the diagnosed chromosome abnormalities in this unselected primary population of 2.2 million people is reported. Five hundred and eighty‐nine chromosome abnormalities were detected in a consecutive series of 6092 karyotypes performed (9.7%). This figure is significantly lower than that found in most other reported series where case selection for karyotyping is determined by clinical criteria. In this current study the annual diagnostic rate for chromosome abnormalities was 5.41 per 100,000 of the general population. Cumulative frequency histograms for all types of chromosome abnormality, by age, are presented: In current practice, 32% of chromosome abnormalities are not diagnosed until adult life. Fifty percent of cases of chromosome abnormality (of all types) remain undiagnosed by the age of 1 year, in spite of a relatively liberal acceptance rate on the part of laboratories offering routine karyotyping services. It is concluded that a positive diagnostic rate greater than 10%, in routine chromosome laboratories, probably indicates that more than half the true cases of chromosome abnormality in a population are being missed.
Human hair follicles may be used for population screening of heterozygotes of glucose‐6‐phosphate dehydrogenase deficiency
Authors: Vermorken A. J. M. , Markslag A. M. G. , Goos C. M. A. A. , Miguel A. , Ramon M. , Petitpierre E.
Published: July 2010

The carrier status for glucose‐6‐phosphate dehydrogenase deficiency can still be detected with the use of hair follicles after a period up to 10–14 days after plucking, even under conditions of temperature and humidity that are encountered in tropical countries, where the disease is most common. Furthermore, it is shown that the hair colour or age of the donor has no influence on the enzyme activity. As a consequence, the hair follicle is indeed suitable for screening in rural areas since mailing to existing medical centres is possible.
Body height in Turner's syndrome
Authors: Pelz Lothar , Timm Dietrich , Eyermann Ellen , Hinkel Georg Klaus , Kirchner Margitta , Verron Gunther
Published: July 2010

Disease‐specific growth curves for Turner's syndrome were calculated by means of 2nd order homogeneous differential equations with constant coefficients, taking different cytogenetical subtypes into account. Comparison of these growth curves between X‐monosomic (n=64) and 46,XX/45,X‐mixoploid (n = 20) patients reveals no differences, in contrast to the commonly accepted opinion.
A note on association of Bf and glomerulonephritis
Authors: Papiha S. S. , Rashid H. U. , Roberts D. F. , Kerr D. N. S.
Published: July 2010

In a study of 86 histologically defined glomerulonephritis patients, a striking association between the BfF allele and glomerulonephritis has been found. There is also an enhanced genetic predisposition to glomerulonephritis in individuals with rare Bf alleles. The role of the chromosome 6 loci in the pathogenesis of the disease is emphasized.
Hemophilia A and B — two years ex‐perience of genetic counselling and prenatal diagnosis
Authors: Ljung Rolf , Holmberg Lars , Gustavii Björn , Philip John , Bang Jens
Published: July 2010

Haemophilia A. Thirty‐one pregnant women, obligate or probable carriers of haemophilia A, requested prenatal diagnosis if sex determination showed the foetus to be a male. In 11 of the 31 cases the foetuses were females; in two, the genetic variant of the disease rendered prenatal diagnosis impossible; and in two, the mother aborted spontaneously. From the remaining 16 male foetuses, blood samples were obtained in uteri in the 17th to 20th week of gestation. Examination of the samples showed that 11 of the foetuses were unaffected and five affected. Haemophilia B. Three carriers of haemophilia B had male foetuses. Examination of foetal blood obtained in utero showed that these three foetuses were affected. Confirmation. All women with an affected foetus requested termination of pregnancy. In one of thecdses of abortion, no blood was obtained for confirmative examination. In the remaining cases, the prenatal prediction was confirmed in the abortus or in the child after birth; three women are still pregnant.
Fertility in patients with X chromosome deletions
Authors: Fryns J. P. , Kleczkowska A. , Petit P. , van den Berghe H.
Published: July 2010

Three fertile, non‐mosaic patients with partial monosomy of an X‐chromosome (two with Xp deletion with breakpoints at Xpl 106 and Xp2101, respectively, and one with a del(Xq25)) were found among 12 females with Xp deletion and three with Xq deletion investigated in this laboratory after the advent of banding techniques. Four phenotypically normal children resulted from a total of seven pregnancies in these women. Three of the children were chromosomally normal and one girl presented the same del(Xp) as her mother. The possibility of having genotypically and phenotypically normal offspring should be taken into account in the management and genetic counseling of children and females with X‐chromosome deletions.
Basal cell carcinoma in a patient with intestinal polyposis
Authors: Michels Virginia V. , Stevens J. Clarke
Published: July 2010

A 22‐year‐old female, with multiple polyposis of the colon and two central nervous system tumors, also suffered from recurrent basal cell carcinoma. The purpose of this report is to alert physicians to the possibility that basal cell carcinoma occurring at an unusually young age may be another manifestation of the familial polyposis syndromes.
Digital clubbing, hyperhidrosis, acro‐osteolysis and osteoporosis. A case resembling pachydermoperiostosis
Authors: Sirinavin Ckintana , Buist Neil R. M. , Mokkhaves Premrudee
Published: July 2010

We report a Cambodian girl with digital clubbing, profuse hyperhidrosis, and joint and leg pain and swelling. She also had extensive acro‐osteolysis of distal phalanges as well as generalized osteoporosis. There was no other affected person in the family, but her parents were first cousins. Although the X‐ray changes are unusual, this patient probably represents a case of pachydermoperiostosis, either occurring as a new mutation or inherited as an autosomal recessive syndrome.
A fourth case of ring chromosome 7
Authors: DeLozier Célia D. , Theintz Gérald , Sizonenko Pierre , Engel Eric
Published: July 2010

An 8‐year‐old child with a ring chromosome 7 is presented, the first female and the fourth such individual to be described. The associated anomalies were rather benign: she presented with short stature, minor skeletal alterations, and normal intelligence. The only truly striking feature was the presence of multiple large, pigmented naevi, suggestive of a hamartomatous origin, but unlike those typical of any particular syndrome. Though other ring 7 patients have had naevus flammeus, and one had cafk‐au‐lait spots, our proband is the first with an anomaly of chromosome 7 to have such extensive lesions. These four cases of ring 7, which show great phenotypic variation, are reviewed, and the clinical presentation of the proband is also compared with that of patients suffering from terminal, interstitial and translocation‐derived 7p and 7q deletions. The formation and behaviour of ring chromosomes are discussed, as are the cytogenetic factors which may influence their phenotypic expression.
Lenz microphthalmia — a case report
Authors: Baraitser M. , Winter R. M. , Taylor D. S. I.
Published: July 2010

A single case of Lenz microphthalmia is presented in order to add to the sparse literature on the dysmorphic features of this X‐linked condition.
A familial paracentric inversion in the short arm of chromosome 3: a case report
Authors: Peters‐Slough M. F. , Planteydt H. T. , Timmerman M. J. , Vooren M. J. V.D.
Published: July 2010

The present report describes a 46,XX,inv(3)(p13p25) karyotype in a 4.5year‐old girl with growth retardation and in her phenotypically normal mother.
Genetics, pathoanatomy and prenatal diagnosis of Potter I syndrome and other urogenital tract diseases
Authors: Schmidt W. , Schroeder T. M. , Buchinger G. , Kubli F.
Published: July 2010

We report on 12 early prenatal diagnoses of “Potter syndrome” and other severe fetal kidney diseases by ultrasonic observations of persistent oligohydramnios and absence of kidney function; seven pregnancies were terminated. These cases are discussed together with others observed in a total of 23 families. Special attention is given to the difficulty of classifying the various kidney diseases pathoanatomically, and also of determining the recurrence risk in the affected families. For genetic counselling, the possibility of early prenatal diagnosis is a practical solution to this problem. Routine ultrasound supervision of pregnancies can already detect a first, sporadic case of the various kidney diseases.
Platelet abnormalities in Down's syndrome
Authors: More Raphael , Amir Naomi , Meyer Shirley , Kopolovic Juri , Yarom Rena
Published: July 2010

Nine individuals with Down's syndrome and 12 normal children were studied. Platelets from Down's syndrome (DS) were smaller than normal and had reduced numbers and volumes of electron dense bodies. Whole cell and dense body calcium levels were lower than normal, while platelet surface net negative charge and anionic sites were found to be elevated in DS platelets. The findings suggest a calcium‐related membrane abnormality as one of the defects in DS platelets.
Low chiasma frequency as an aetiological factor in male infertility
Authors: Mićić Miroslava , Mićić Sava , Diklić Vukosava
Published: July 2010

Among 120 meiotic analyses of infertile men there were three cases with a particular meiotic anomaly: low chiasma count at diakinesis and spermatogenic arrest. All clinical findings, hormonal analyses and karyotypes from peripheral blood were normal. Meiotic studies showed that pachytene pairing was complete, but in diakinesis the mean number of chiasmata per cell was significantly lowered, chromosomes were fragmented and univalents could frequently be found. In all three cases azoospermia was the consequence of spermatogenic arrest, which occurred after diakinesis‐metaphase I.
Measuring the genetic contribution of a single locus to a multilocus disease
Authors: Rotter Jerome I. , Landaw Elliot M.
Published: July 2010

An increasing number of diseases are being demonstrated to be due to determinants at more than one genetic locus. It thus becomes of interest to determine the genetic contribution of a specific single locus. A method of estimating a “coefficient of genetic contribution” is described herein, based on a comparison of monozygotic twin concordance data for a specific disease, the empirical sibling recurrence risks, and the sharing of identical by descent genes at the specific locus of interest by pairs of siblings who are both affected. The value of the method is that it requires relatively few assumptions, and does not require knowledge of the mode of inheritance of disease susceptibility at the gene locus of interest. If there are major environmental determinants, this method will give a lower bound for the single locus of interest. To illustrate the method, it is applied to two specific diseases, insulin dependent diabetes mellitus (IDDM) and gluten‐sensitive enteropathy (GSE), and a specific locus, the HLA gene complex. The best estimates would appear to be that the HLA “genes” provide a coefficient of 60% for IDDM susceptibility, but only 30% for GSE. A possible reason for these differences is the markedly increased disease susceptibility of the DR3/DR4 heterozygote for IDDM.
Stimulation of the Synthesis of Ribosomal Proteins in Regenerating Rat Liver with Special Reference to the Increase in the Amounts of Effective mRNAs for Ribosomal Proteins
Authors: NABESHIMA Yo‐ichi , OGATA Kikuo
Published: July 2010

Normal and partially hepatectomized rats were pulse labeled for 15 min with [14C]leucine and [3H]leucine respectively. Both kinds of liver homogenates were mixed and the ribosomal protein fraction was purified from the mixed homogenate by chromatographic procedures. The 3H/14C ratio of this fraction was about three times higher than that of total protein, indicating that the synthesis of ribosomal proteins is selectively increased in regenerating rat liver.

The free polysomes from normal or regenerating rat livers were incubated with [3H]leucine in the presence of regenerating rat liver supernatant. Ribosomal proteins were then purified, finally by two‐dimensional acrylamide gel electrophoresis. Biosyntheses of most of ribosomal proteins by regenerating rat liver polysomes were about 2.5 to 3.6 times higher than those by normal rat liver polysomes.

Using a wheat germ cell‐free system, the template activities of poly(A)‐containing mRNAs for ribosomal proteins were compared between normal and regenerating rat livers. The template activities at 6, 12, 18, 24 and 48 h after partial hepatectomy were about 1.3, 1.8, 2.4, 1.5 and 1.3 times higher, respectively, than the activity of normal rat liver. The extents of increase in the template activity of poly(A)‐containing mRNAs for most of individual ribosomal proteins separated by two‐dimensional gel electrophoresis were not so different at 18 h after the operation and the average template activity was 2.8 times higher than that of normal rat liver. The enhanced activity of regenerating rat liver for ribosomal protein synthesis is mainly caused by the increase in the apparent concentrations of mRNAs for ribosomal proteins.
The Role of the Light‐Harvesting Chlorophyll a/b ‐Protein Complex in Chloroplast Membrane Stacking
Authors: RYRIF Ivan J. , ANDERSON Jan M. , GOODCHILD D. J.
Published: July 2010

The major intrinsic protein from spinach chloroplast membranes, the light‐harvesting chlorophyll a/b‐protein complex, contains two distinct polypeptides of Mr 23500 and 26000 and 31 % lipid by weight, comprising five diacyl lipids and seven chlorophylls, together with some carotenoids, per 26000‐Mr polypeptide. The chlorophyll a/b ratio is 1.1. Low‐temperature fluorescence emission spectra of the light‐harvesting complex revealed a major peak at 681 nm with a shoulder of variable intensity at 695 nm. The 695‐nm emission has been correlated with a progressive aggregation of the complex into two‐dimensional, semi‐crystalline sheets.

To determine the role of the light‐harvesting complex in cation‐dependent thylakoid stacking, the purified complex has been quantitatively incorporated into liposomes containing the four major chloroplast diacyl lipids using a simple freeze‐thaw technique. The proteoliposomes appeared largely as unilamellar vesicles, with diameters between 0.1 and 0.8 μm. Freeze‐fracture analysis showed intra‐membrane particles of 8–10 nm corresponding to the incorporated complex. Both monovalent and divalent cations caused an immediate aggregation of the proteoliposomes, which was reversed at low cation concentrations and was largely inhibited by prior trypsin treatment. Since lipid vesicles themselves showed none of these effects, it is concluded that surface‐exposed polypeptide regions of the light‐harvesting complex are directly involved in thylakoid stacking in vivo.
Generation of an Electrochemical Proton Gradient by Lactate Efflux in Membrane Vesicles of Escherichia coli
Authors: TEN BRINK Bart , KONINGS Wil N.
Published: July 2010

The ‘energy recycling model’ (Michels et al. (1979) FEMS Microbiol. Lett. 5, 357–364] postulates the generation of an electrochemical gradient across the bacterial cytoplasmic membrane by carrier‐mediated efflux of metabolic endproducts in symport with protons.

Experimental evidence for this model is presented. In membrane vesicles from Escherichia coli ML 308–225 l‐lactate translocation (both uptake and efflux) is carrier‐mediated. The H+/t‐lactate stoichiometry varies, depending on the external pH, between 1 and 2. This change in stoichiometry is most likely the result of a protonation of the lactate carrier protein. This process has a pK of 6.75. l‐Lactate efflux from membrane vesicles, loaded with 50 mM potassium l‐lactate, results at an external pH of 6.6 in an 11‐fold accumulation of proline inside the vesicles. This accumulation is completely inhibited by the uncoupler carbonyl cyanide p‐trifluoromethoxyphenylhydrazone. The uptake of proline is not the result of a potassium or an osmotic gradient.

At an external pH of 6.6 efflux of l‐lactate from the vesicles leads to the generation of an electrical potential across the membrane of ‐ 55 mV, as is demonstrated from the accumulation of the lipophilic cation tetraphenylphosphonium.
Cyanine Dye Measurement of a Light‐Induced Transient Membrane Potential Associated with the Metarhodopsin II Intermediate in Rod‐Outer‐Segment Membranes
Authors: BENNETT Nelly , MICHEL‐VILLAZ Michel , DUPONT Yves
Published: July 2010

The fluorescent dye 3,3′‐dipropylthiodicarbocyanin iodide [diS‐C3−(5)] is used as a probe of fast membrane potential variations in the study of rod‐outer‐segment membranes. The formation of metarhodopsin II is found to be associated with the generation of a transmembrane potential, which is dissipitated by ionic movements across the membrane; its risetime is very similar to that of the protonation of the protein, which is also associated with the formation of metarhodopsin II.
Non‐specific Biosynthesis of Gammacerane Derivatives by a Cell‐Free System from the Protozoon Tetrahymena pyriformis
Authors: BOUVIER Pierrette , BERGER Yves , ROHMER Michel , OURISSON Guy
Published: July 2010

A cell‐free system from the protozoon Tetrahymena pyriformis was incubated with either [12‐3H]squalene or (RS)‐2,3‐epoxy‐2,3‐dihydro‐[12,13‐3H]squalene. Squalene was cyclized into tetrahymanol whereas racemic squalene epoxide was transformed into gammacerane‐3α,21α‐diol and gammacerane‐3β,21α‐diol. After cyclization of (RS)‐2,3‐epoxy‐2,3‐dihydro‐[3‐3H]squalene, both epimeric gammaceranediols were labelled with a tritium atom located at C‐3, showing that no isomerization via a 3‐oxo compound occurred.

The proton NMR spectra of the cyclization products of synthetic (2E, 22E)‐(1,1,1,24,24,24‐2H6) squalene and (RS)‐(22E)‐2,3‐epoxy‐2,3‐dihydro‐(1,1,1,24,24,24‐2H6) squalene show that squalene and the (3S)enantiomer of its epoxide are cyclized in an all pre‐chair conformation, whereas tae (3R) enantiomer of squalene epoxide is cyclized in a pre‐boat conformation as concerns the cycle A.

The squalene cyclase of T. pyriformis presents the sane lack of substrate specificity as the cyclase of Acetobacter pasteurianum: in addition to squalene, its normal substrate, it also cyclizes both enantiomers of its epoxide. This conformational versatility is characteristic of squalene cyclases but no longer exists in the squalene epoxide cyclases from eukaryotes.
Nucleotide Sequences of Wheat‐Embryo Cytosol 5‐S and 5.8‐S Ribosomal Ribonucleic Acids
Authors: MACKAY Ron M. , SPENCER David F. , DOOLITTLE W. Ford , GRAY Michael W.
Published: July 2010

The nucleotide sequences of wheat embryo 5.8‐S and 5‐S rRNAs have been determined with the use of several techniques, including classic analysis of oligonucleotides generated by ribo‐nuclease T1 and resolution on gels of termiNatly labelled RNA partially degraded with ribonucleases or with chemical reagents. The sequence of wheat embryo 5.8‐S rRNA was found to be p(C)‐A‐C‐ 5.8‐S RNAs, the accommodation of this sequence by current secondary structural models, and the significance of the observed post‐transcriptional modification pattern are discussed. The sequence . This sequence is compared to 5‐S rRNA Sequences previously published for wheat and several other angiosperms.
Evidence for Two Different Reactive Sulfhydryl Groups in the ATP‐Binding Sites of (Na++ K+)‐ATPase
Authors: PATZELT‐WENCZLER Rosemarie , SCHONER Wilhelm
Published: July 2010

The disulfide of thioinosine triphosphate, (SnoPPP)2 is a substrate of (Na++ K+)‐ATPase from pig kidney.

Binding of (SnoPPP)2 and of the β,γ‐imido or β,γ‐methylene analogues, (SnoPP[NH]P)2 or (SnoPP[CH2]P)2, to (Na++ K+)‐ATPase in the presence of 10 mM EDTA results in an inactivation of the enzyme. The inactivation is temperature‐dependent and has an activation energy of 95.5 kJ/mol with (SnoPPP)2 as substrate.

The inactivation proceeded with all disulfide analogues of ATP with two different velocities. Identical inactivation rate constants k2 were found for all substances for the rapidly inactivating part (k′2= 2.9–4.7 × 10−3 s−1) and the slowly inactivating part (k″2= 2.0−2.3 × 10−4 s−1). From the analysis of the inactivation kinetics identical dissociation constants were found for both sites. The dissociation constants of the complexes between enzyme and ATP analogue inactivating the enzyme slowly were: (SnoPPP)2= 18.6 μM, (SnoPP[NH]P)2= 38.8 μM and (SnoPP[CH2]P)2= 63.3 μM.

ATP protected both sites against the inactivation by the disulfide analogues of ATP. From the protective action of ATP at 37° C against the inactivation, a dissociation constant of the enzyme‐ATP complex of 2.95 μM was calculated for the rapidly inactivating site and of 77 μM for the slowly reacting site.

The total capacity of the sulfhydryl groups reacting with the ATP analogue (SnoPPP)2 is four‐times higher than the capacity of the phosphointermediate and the with (SnoPPP)2 rapidly reacting site (high, affinity ATP‐binding site).

It is concluded that (SnoPPP)2 as well as (SnoPP[NH]P)2 and (StoPP[CH2]P)2 are ATP affinity labels of the high‐affinity and low‐affinity ATP‐binding sites of (Na++ K+)‐ATPase. Since dithiothreitol reactivates (Na++ K+)‐ATPase after inactivation by (SnoPPP)2 [Patzelt‐Wenezler and Schoner (1975) Biochim. Biophys, Acta, 403, 538–513] it is assumed that (Na++ K+)‐ATPase contains two different reactive types of sulfhydryl groups in the ATP‐binding sites. Tte sulfhydryl group, may interact with the 6‐amino group of the purine moiety of ATP.
Formation of Fructose 2,6‐Bisphosphate from Fructose 1,6‐Bisphosphate by Intramolecular Cyclisation followed by Alkaline Hydrolysis
Authors: VAN SCHAFTINGEN Emile , HERS Henri‐Géry
Published: July 2010

The method described by Pontis and Fischer [Pontis, H. G. and Fischer, C. L. (1963) Biochem. J. 89, 452–459] for the conversion of fructose 1‐phosphate into fructose 2‐phosphate has been applied to fructose 1,6‐bisphosphate. This procedure allowed us to prepare fructose 2,6‐bisphosphate in millimolar amounts. This ester had all the chemical and biological properties previously described for the natural stimulator of phosphofructokinase extracted from rat liver [Van Schaftingen, E., Hue, L., and Hers, H. G. (1980) Biochem. J. 192, 897–901].
Demonstration of Physical Interactions between Consecutive Enzymes of the Citric Acid Cycle and of the Aspartate‐Malate Shuttle
Authors: BEECKMANS Sonia , KANAREK Louis
Published: July 2010

By means of covalently immobilized fumarase and mitochondrial or cytoplasmic malate dehydrogenase we were able to detect physical interactions between different enzymes of the citric acid cycle (fumarase with malate dehydrogenase, malate dehydrogenase with citrate synthase and fumarase with citrate synthase) and between the enzymes of both mitochondria) and cytoplasmic halves of the aspartate‐malate shuttle (aspartate aminotransierase and malate dehydrogenase). The interactions between fumarase and malate dehydrogenase were also investigated by immobilizing one enzyme indirectly through antibodies bound to Sepharose‐protein A. Our results are consistent with a model in which maximally four molecules of malate dehydrogenase are bound to one fumarase molecule. This complex is able to bind either citrate synthase or aspartate aminotransferase. We propose that these enzymes bind alternatively, in order to allow the cell to perform citric acid cycle or shuttle reactions, according to its needs. The physiological meaning and implications on the regulation of metabolism of the existence of a large citric acid cycle/malate‐aspartate shuttle multienzyme complex are discussed.
Helical Periodicity of DNA, Poly(dA)·Poly(dT) and Poly(dA‐dT)·Poly(dA‐dT) in Solution
Authors: STRAUSS Franqois , GAILLARD Claire , PRUNELL Ariel
Published: July 2010

Helical periodicity of DNA, poly(dA)·poly(dT) and poly(dA‐dT)·poly(dA‐dT) has been measured in solution by using the band shift method of Wang [Wang, J. (1979) Proc. Natl Acad. Sci. USA, 76, 200–203]. The method makes use of the effect, on the superhelicity of closed circular DNA molecules, of the insertion of specific nucleotide sequences of known length. The method was applied to a variety of recombinant plasmid DNAs which were constructed by inserting DNA, poly(dA)·poly(dT) or poly(dA‐dT)·poly(dA‐dT) into pBR322 DNA. When compared to DNA, poly(dA)·poly(dT) was found to have a smaller pitch (by about 0.5 base pair/turn), whereas poly(dA‐dT)·poly(dA‐dT) has a slightly larger pitch (by 0.1 base pair/turn). These features correlate well with the known ability of the alternating copolymer to reconstitute nucleosomes upon incubation with histones, in contrast to the non‐alternating one which fails to do so. Finally, a detailed analysis of the principles underlying the methods developed by Wang [reference quoted above and Wang, J. (1978) Cold Spring Harb. Symp. Quant. Biol. 42, 29–33] leads to an increase in the estimate of the helical periodicity of DNA of 0.15 base pair/turn, over the reported value of 10.4 base pairs/turn (references quoted above). This essentially accounts for the discrepancy observed with the value of 10.6 base pairs/turn obtained by nuciease digestion of DNA immobilized on a surface [Rhodes, D. & Klug, A. (1980) Nature (Lond.) 286, 573–578].
Role of Sialic Acid in the Mobility of Membrane Proteins Containing O‐Linked Oligosaccharides on Polyacrylamide Gel Electrophoresis in Sodium Dodecyl Sulfate
Authors: GAHMBERG Carl G. , ANDERSSON Leif C.
Published: July 2010

The major sialoglycoprotein of the human red‐cell membrane, glycophorin A, contains 15 O‐glycosidically linked oligosaccharides and one N‐glycosidic oligosaccharide. The protein shows a decreased mobility on polyacrylamide gel electrophoresis in sodium dodecyl sulfate after neuraminidase treatment of thc nondenatured protein.

The molecular mechanism behind this phenomenon has been elucidated. Neuraminidase treatment of glycophorin A in intact cells or after solubilization in buffers containing Triton X‐100 resulted in conversion of the predominant tetrasaccharide N‐acetylneuraminosylα2 ‐3galactosylβl‐ 3(N‐acetylneuraminosylα2 ‐ 6)‐N‐acetylgalactosamine to the trisaccharide galactosylβl ‐ 3(N‐acetylneuraminosylα2 ‐ 6)‐N‐acetylgalactosamine and the disaccharide galactosylβl ‐ 3‐N‐acetylgalactosamine. After denaturation with sodium dodecyl sulfate, Vibrio cholerae neuraminidase also liberated the N‐acetylgalactosamine‐bound sialic acids. Such treatment resulted in increased electrophoretic mobility.

The results show that distal sialic acids linked to galactose are readily available to neuraminidase, and that their negative charge gives an increased electrophoretic mobility in polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. In contrast, most of thc N‐acetylgalactosamine‐linked sialic acids of glycophorin A are not liberated by neuraminidase without denaturation of the substrate. Like sialic acids of complex‐type oligosaccharides the decreased electrophoretic mobility caused by them is exclusively due to their mass while no significant contribution by the charge was seen.
Routes of Flavodoxin and Ferredoxin Reduction in Escherichia coli
Authors: BLASCHKOWSKI Hans P. , KNAPPE Joachim , LUDWIG‐FESTL Monika , NEUER Gabriele
Published: July 2010

Flavodoxin and ferredoxin become reduced in Escherichia coli cells by oxidoreductase reactions which use pyruvate and NADPH as electron donor substrates. The two enzymes, which are minor proteins of this organism, were measured through the reduced flavodoxin‐dependent activation of pyruvate formate‐lyase. The NADPH‐dependent enzyme, obtained homogeneously through Procion‐red affinity chromatography, was identified as the flavoprotein ‘component R’ described previously by Fujii and Huennekens [J. Biol. Chem. 249, 6745–6753 (1974)]. The pyruvate‐dependent enzyme was identified as CoA‐acetylating pyruvate; flavodoxin (ferredoxin) oxidoreductase. Its catalytic properties in the forward. reverse, and the 14CO2‐pyruvate exchange reaction are reported.

The dihydro form of flavodoxin was characterized as the particular species involved in the activation of pyruvate formate‐lyase. The activation process still occurs with 70% of maximal efficiency when the ratio [NADPH]/([NADP] + [NADPH]) is fixed at the intracellular ‘anabolic reduction charge’ value of 0.45, in conjunction with the NADPH‐dependent enzyme. The [2Fe‐2S] ferredoxin, though being readily used as electron acceptor of both oxidoreductases and having a redox potential similar to flavodoxin, proved incompetent in mediating the activation of pyruvate formate‐lyase.