Cerebral and ocular abnormalities with anterior pituitary insufficiency of familial nature

Three families presenting one or several cases of brain or ophthalmic abnormalities and an hypopituitarism at least by one of the members have been observed. In the first family, the mother and one of her sons present bilateral choroidoretineal coloboma with amblyopia; one of these two suffers as well from panhypopituitarism. In the second family two premature twins, a brother and his sister, present a syndrome with hypophyseal dwarfism and ophthalmic abnormalities, consisting in the boy's case in an peripapillary depigmentation with no visible sight trouble whereas girl's is showing an extreme microphthalmia with major mental retardation. In the third family two 2nd degree cousins present a panhypopituitarism but only one of the two reveals through neuroradiological investigations corpus callosum and septum lucidum agenesia. The karyotype is normal in all the cases. An hereditary mechanism appears clearly in the first family. It is possible in the second, probable in the third one.     

A new formulation for the project scheduling problem under limited resources

In this paper we propose a new formulation for the Resource Constrained Project Scheduling Problem (RCPSP) and minimum makespan objective. The new formulation exploits three variables, one associated with the start time of an activity, one associated with the finish time of an activity, and the last one associated with the amount of an activity in progress at a given time. We provide an extensive experimentation, and a comparison with known mathematical formulations for the RCPSP in the literature.     

Duplication of the short arm of chromosome 9. Analysis of five cases

Summary Five females with duplication of the short arm of one chromosome 9 are reported, one tetrasomic and four trisomic for 9p. The tetrasomy is due to an isochromosome 9p while the trisomies are due in one case to an intrachromosomal duplication present in lymphocytes but not in fibroblasts, two are secondary to translocations with chromosomes 22 and 13 respectively, and one is a mosaic with a cell line with an additional deleted chromosome 9 present in lymphocytes and fibroblasts. This analysis indicates that duplications 9p may result in impairment of ovarian function. The phenotypic differences between trisomy and tetrasomy 9p are discussed.     

Preparation and immunoephelometric quantitation of fibrinogen in rabbits]

Pure rabbit fibrinogen was prepared by a method involving two ammonium sulfate precipitations, one 2 M phosphate buffer precipitation, one DEAE cellulose chromatography and lastly one Sepharose 6 B chromatography. The aminoacid composition was determined and an immunonephelemetric assay was proposed. This assay followed an accurate determination of fibrinogen concentration in a rabbit with inflammatory reaction.     

Préparation et dosage immunonéphélémétrique du fibrinogène de lapin

Pure rabbit fibrinogen was prepared by a method involving two ammonium sulfate precipitations, one 2 M phosphate buffer precipitation, one DEAE cellulose chromatography and lastly one Sepharose 6 B chromatography. The aminoacid composition was determined and an immunonephelemetric assay was proposed. This assay allowed an accurate determination of fibrinogen concentration in a rabbit with inflammatory reaction.     

Astrogliosis in different zones of the spinal cord gray matter after sciatic nerve axotomy in the newborn rat: a morphometric and immunohistochemical study

Astrocytic response following unilateral sciatic nerve axotomy was examined in the spinal gray matter of newborn rats. Using an antiserum to glial fibrillary acidic protein (GFAP), immunoreactive astrocytes were studied in the ventral, dorsal and transitional region between the dorsal and ventral gray matters (TDVG) at intervals of one day, one week, two weeks and one month postaxotomy. The axotomized side showed an obvious increase in the number of immunoreactive astrocytes at one week, two weeks and one month after surgery. The numerical density per area of the glial cells (N(a)) was determined in all groups on both the intact and axotomized sides, and it increased in all groups at the axotomized sides. The percentage of glial cell increase (Pgi) was also determined. At the ventral horn Pgi increased at day one and continued to increase in all groups, while the increase in TDVG and the dorsal horn occurred at later time points. The total motoneuron count in the ventral horn at the axotomized and intact sides was done at all time points, and the percentage of motoneuron reduction (Pmr) was calculated, the highest Pmr being noticed at one month (41%). A nonlinear regression for Pmr and Pgi showed that the rate of Pgi was approximately double that of Pmr. The rate of glial cell increase at each time point (one day, one week, two weeks and one month groups) was calculated, and the highest rate of glial cell increase in the ventral horn occurred one week after axotomy, while the highest rate in the dorsal horn and TDVG occurred at the second week. The conclusion of the study is that there may be an initial post-axotomic proliferative phase of the glial cells, which was followed by a differentiation phase. Also a gradient of an increase in the rate glial cell proliferation was noticed from the ventral horn toward the dorsal horn, maybe due to stimulation by a paracrine factor.     

Use of plasmid profiling as a typing method for epidemiologically related Clostridium perfringens isolates from food poisoning cases and outbreaks

Plasmid profiling was used for the characterization of Clostridium perfringens isolates involved in disease outbreaks. The usefulness of this technique was demonstrated by the retrospective examination of food and patient isolates from 10 cases and outbreaks from 1984 to 1991. The origin of three outbreaks could be clearly confirmed due to identical plasmid profiles in all isolates. In one outbreak identical plasmid patterns were found between one food and one patient isolates, while one plasmid was missing in the second patient isolate. In an additional two cases a relationship between food and patient isolates is likely, if the possibility of the loss of one plasmid in one of the isolated strains is considered. In one outbreak two faecal isolates could be related to an isolate from one of the two foods implicated as outbreak source; isolates from the other food and a third faecal sample could not be linked to any other isolate. The results from three outbreaks were largely inconclusive because plasmids were not present either in all or in some of the isolates.     

Genetic length and interference in telo-substituted interchange heterozygotes of rye

Substituting one of the (sub)metacentric chromosomes of a simple interchange complex by the two corresponding telocentrics marks one of the unchanged arms, one of the interchange segments and one of the interstitial segments. When the two telocentrics can be distinguished and when only infrequently MI configurations are formed for which more than a single origin is possible, rather exact estimates of the frequency of occurrence of chiasmata in the six segments can be obtained. When the two telocentrics can not be distinguished and in addition the frequency of MI configurations with more than one possible origin is not negligible, the analysis is more complex. With some previous knowledge of the interchange and some simplification an acceptable simple solution remains possible. — Of both cases an example for rye, Secale cereale, is given, together with an analysis of interference between these segments, and a conversion of probabilities of being bound at MI to genetic length.     

The K+-induced apparent heterogeneity of high-affinity nucleotide-binding sites in (Na+ + K+)-ATPase can only be due to the oligomeric structure of the enzyme

K+ induces an apparent heterogeneity among an otherwise homogeneous population of nucleotide-binding sites in (Na+ + K+)-ATPase preparations from pig kidney. With the help of ouabain we show that this heterogeneity cannot be due to a mixture of different and independent sites and conclude that each enzyme molecule must contain two nucleotide site-containing units that show interaction. Na+ induces an apparent heterogeneity among an otherwise homogeneous population of ouabain-binding sites. The argument is, therefore, extended to include one ouabain site on each of the structural units that bind nucleotide. All these structural units are shown to hydrolyse substrate at identical rates. Using the presently available molecular weight data, it is concluded that the enzyme is composed of two subunits each possessing one nucleotide-binding site, one ouabain-binding site, one alpha-peptide and the capacity for hydrolysing ATP and p-nitrophenyl phosphate.     

Defects in synthesis, phosphorylation, and maturation of acid alpha-glucosidase in glycogenosis type II

Glycogenosis type II is an inherited lysosomal storage disease with acid alpha-glucosidase deficiency as the primary defect. Using cultured skin fibroblasts, we have studied the biosynthesis of acid alpha-glucosidase in clinically different forms of this disease. Three unrelated patients were identified (one with an infantile, one with a juvenile, and one with an adult form of the disease) producing normal quantities of the 110-kDa precursor form of acid alpha-glucosidase. However, post-translational modification to mature 76-kDa enzyme protein was either completely deficient or extremely inefficient. No abnormalities were observed in glycosylation of the mutant precursors, as measured by the incorporation of [3H]mannose, but phosphorylation was only detectable for the precursor synthesized by fibroblasts from the juvenile patient. In three other patients (one with a juvenile and two with adult forms of glycogenosis type II) apparently reduced synthesis of precursor protein was observed, but the processing to mature enzyme seemed to be undisturbed. Finally, neither precursor nor mature forms of acid alpha-glucosidase were detectable in one particular case of infantile glycogenosis type II. The studies reveal an unexpected degree of genetic heterogeneity in this disease and identify various mutants which could be of importance to further elucidate the biosynthetic events during lysosomal enzyme formation.     

Mutations of the P53 gene, including an intronic point mutation, in colorectal tumors.

In this study, analysis of structural changes of the p53 gene in colorectal tumors revealed point mutations detected in 8 of 14 carcinomas and 2 of 2 adenomas. Of these 10 cases with point mutations, eight had one or more missense mutations, one had a nonsense mutation, and the remaining one had, interestingly, an intronic point mutation with subsequent activation of a cryptic splice donor site in the flanking exon. This report contains the first identification of an intronic point mutation of the p53 gene in a colorectal cancer case.     

Medical History: Arthritis in Saxon and mediaeval skeletons

Examination of 400 Saxon, Romano-British, and mediaeval skeletons from seven archaeological excavations in the west of England showed an unexpectedly high incidence of osteoarthritis and osteophytosis. Three skeletons had evidence of an erosive peripheral arthritis—one with probable gout, one probable psoriatic arthropathy, and one with possible rheumatoid arthritis. The pattern and types of rheumatic disease, and the resultant disability, were apparently different. An exuberant form of large joint osteoarthritis was common and rheumatoid arthritis and similar diseases rare.     

Hare on potentiality: a rejoinder

Richard Hare's comment on an article by Lockwood in Bioethics (article and comment appeared in 1988 Jul; 2(3): 187-213, 214-226) pinpoints their crucial disagreement over the extent to which one is entitled to sacrifice the potential for worthwhile life of individuals whose actuality is already an established fact. Lockwood argues that, even though we can all feel gratitude toward our parents for our existence, the obligation one has towards an actual individual not to prevent his or her own potentiality for human life from being realized is far stronger than any obligation one has to bring into existence, or not to prevent from coming into existence, an otherwise merely possible individual with a similar potentiality.     

Ultrastructucal Features of the Neoplastic Sertoli Cell in a Dog

Although the Sertoli cell tumour is a common testicular neoplasm in the dog, accounting for 32% of testis tumours in one study (Nielsen & Lein 1974), we have only found one report (von Bomhard et al. 1978) on the ultrastructure of this tumour in the dog. The present paper, describing electron microscopic features of one such tumour in an undescended testis of an 11-year-old dog, provides some new information on the ultrastructure of the neoplasm.     

The human factor VII gene is polymorphic due to variation in repeat copy number in a minisatellite

The gene coding for human factor VII, a vitamin K-dependent coagulation factor, contains five minisatellite imperfect tandem repeats with monomer element lengths ranging from 14 to 37 bp, and copy numbers ranging from 6 to 52. Three of these repeats are entirely within introns, one is entirely in an untranslated portion of an exon, and one spans an exon-intron border and contains coding sequence. A consensus sequence derived from a comparison of the monomers is similar to a core sequence found in other minisatellites. All of the minisatellites display higher-order periodicities. At least one of these minisatellites is polymorphic. A variation in repeat copy number has been observed in a tandem-repeat region in the seventh factor-VII intron.     

Distribution and development of Brugia malayi in reinfected cats.

At various time periods after an initial exposure to 50 Brugia malayi larvae on one hind foot cats were reexposed to an additional 50 larvae in one of 3 ways: on the previously infected limb only, on the contralateral, uninfected limb only, or on both hind limbs simultaneously. At the time of reexposure uninfected controls were exposed to 50 larvae on one hind foot in a similar manner. From 2 to 4 weeks after reexposure to larvae, the cats were necropsied and the appropriate lymph nodes and vessels examined for adult or developing worms. An existing infection in one limb did not influence early migration or development of larvae introduced into the contralateral leg. Previous infection in the same limb did not consistently result in decreases in the number of developing larvae from the second exposure but did alter the distrubution of larvae. In repeat infections, larvae were consistently located in a moe distal area of the limb than were larvae from an initial infection at a comparable time.     

Risks of acute traumatic intracranial haematoma in children and adults: implications for managing head injuries.

OBJECTIVE--To determine the factors influencing the risk of an acute traumatic intracranial haematoma in children and adults with a recent head injury. DESIGN--Prospective study of incidence of risk factors in samples of patients attending accident and emergency departments and in all patients having an acute traumatic intracranial haematoma evacuated in one regional neurosurgical unit during 11 years. SETTING--Accident and emergency departments in Scotland or Teesside and regional neurosurgical centre in Glasgow. PATIENTS--8406 Adults and children (less than or equal to 14 years) who attended accident and emergency departments and 1007 consecutive patients who had an operation for an acute traumatic intracranial haematoma. Data were complete in 8366 and 960 patients respectively. RESULTS--Overall, children were less at risk than adults (one in 2100 v one in 348 respectively). In both age groups the presence of a skull fracture and changes in conscious level permitted identification of subgroups of patients with widely differing degrees of risk. In children the absolute risk ranged from one in almost 13,000 without a fracture or altered conscious level to one in 12 for a child in a coma and with a fracture; the pattern was similar in adults, the risks in corresponding groups ranging from one in almost 7900 to one in four. CONCLUSIONS--Although children attending hospital after a head injury have a lower overall risk of a traumatic haematoma, the main indicators of risk, a skull fracture and conscious level, are the same as in adults, and the pattern of their combined effect is similar. Guidelines for managing adults with recent head injury may therefore be applied safely to children; with the increasing provision of facilities for computed tomography they should be revised to ensure early scanning of more patients with head injury.     

Shadows of complexity: what biological networks reveal about epistasis and pleiotropy

Pleiotropy, in which one mutation causes multiple phenotypes, has traditionally been seen as a deviation from the conventional observation in which one gene affects one phenotype. Epistasis, or gene–gene interaction, has also been treated as an exception to the Mendelian one gene–one phenotype paradigm. This simplified perspective belies the pervasive complexity of biology and hinders progress toward a deeper understanding of biological systems. We assert that epistasis and pleiotropy are not isolated occurrences, but ubiquitous and inherent properties of biomolecular networks. These phenomena should not be treated as exceptions, but rather as fundamental components of genetic analyses. A systems level understanding of epistasis and pleiotropy is, therefore, critical to furthering our understanding of human genetics and its contribution to common human disease. Finally, graph theory offers an intuitive and powerful set of tools with which to study the network bases of these important genetic phenomena.     

Activity of maturation promoting factor in mammalian oocytes after its dilution by single and multiple fusions

Mouse and porcine fully grown oocytes at metaphase I(MI) were fused to one or more fully grown oocytes of the same species that contained an intact germinal vesicle (GV). In fused cells containing one GV, premature chromosome condensation (PCC) was observed. In fused cells containing more than one GV, germinal vesicle breakdown (GVBD) and PCC were delayed. Fusion of an MI fully grown oocyte with a growing oocyte resulted in rapid PCC, whereas, fusion of an MI fully grown oocyte with more than one growing oocyte resulted in neither PCC nor GVBD. Moreover, MI chromosomes formed a clump of chromatin. Results of these experiments suggest that the delay in GVBD in fusions of MI oocytes with multiple GV-intact oocytes was due to dilution of maturation promoting factor (MPF) by the cytoplasm of the GV-intact oocytes and that the cytoplasm of growing oocytes can inhibit MPF present in MI oocytes.     

Reconstructing an ultrametric galled phylogenetic network from a distance matrix

Given a distance matrix M that specifies the pairwise evolutionary distances between n species, the phylogenetic tree reconstruction problem asks for an edge-weighted phylogenetic tree that satisfies M, if one exists. We study some extensions of this problem to rooted phylogenetic networks. Our main result is an O(n(2) log n)-time algorithm for determining whether there is an ultrametric galled network that satisfies M, and if so, constructing one. In fact, if such an ultrametric galled network exists, our algorithm is guaranteed to construct one containing the minimum possible number of nodes with more than one parent (hybrid nodes). We also prove that finding a largest possible submatrix M' of M such that there exists an ultrametric galled network that satisfies M' is NP-hard. Furthermore, we show that given an incomplete distance matrix (i.e. where some matrix entries are missing), it is also NP-hard to determine whether there exists an ultrametric galled network which satisfies it.