Osteofibrous dysplasia in the newborn. Report of a case.
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Diagnosis, Differential↗
Biomedical subjects
M J Anderson
Publications and source records attributed to M J Anderson.
The role of the National Institutes of Hospital Management in national health care system development: report of an international seminar.
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Academies and Institutes↗
Effect of undocumented and excluded vaccinations on measles immunity in a university population.
Epidemic measles has occurred even in highly vaccinated university and college populations because vaccine efficacy is only 90-95% and some student bodies do not have 100% vaccine coverage. Some institutions have not adopted or enforced a one-dose, preregistration immunization requirement because of the increased administrative burden, although in 1990 a documented two-dose schedule was recommended to increase herd immunity to a critical 93.5-96.0%. Perhaps one documented immunization for all students coupled with an undocumented or excluded pre-1968 one that some students are reporting will result in adequate herd immunity. At the University of South Florida 149 students (group I), after documenting receipt of one immunization, attempted to prove immunity by having an antibody test. They were compared with 181 students who documented two doses (group II) for factors which might influence differences of immunity between the groups after one dose. Undocumented immunizations were estimated by determining the percent of students reporting recent immunizations after allowing for the expected unimmunized percent. Excluded vaccinations were calculated for students born before 1967. Group I had a 98% (95% C.I. 94.2-99.6) immunity. One-third to one-half of both groups had undocumented and excluded immunizations. Some differences identified were not important enough to prevent extrapolation of this high immunity from group I to group II students. One documented live measles vaccination for all students combined with an undocumented or excluded one for some of them may provide adequate herd immunity to prevent measles epidemics on university and college campuses.
Adult↗
Growth suppression mediated by transfection of p53 in Hut292DM human lung cancer cells expressing endogenous wild-type p53 protein.
This study was undertaken to analyze the effect of wild-type p53 transfection on the growth potential of a human lung cancer cell line Hut292DM expressing endogenous wild-type p53. Transfection efficiencies obtained with either the wild-type or a mutant p53 complementary DNA revealed a significant decrease in the number of colonies obtained with the wild-type p53 as compared to the mutant p53 complementary DNA (27%) or control vector DNA only (20%), suggesting that wild-type p53 inhibited the growth of Hut292DM cells. A series of wild-type and mutant p53 transfection clones were then analyzed for the presence and expression of the exogenous p53 gene. Polymerase chain reaction amplification revealed that 98% of mutant p53 transfection clones analyzed contained the exogenous p53 gene as opposed to 47% for wild-type p53 clones. The majority of mutant p53 clones expressed high levels of exogenous p53 mRNA and protein as analyzed by Northern and Western blots, respectively. In contrast, all wild-type p53 clones analyzed failed to express exogenous p53 mRNA transcript or protein of a normal size. Aberrant-size p53 mRNA was detected in two wild-type p53 clones (X833.W2 and W18), and Western blot analysis revealed that these clones expressed truncated p53 proteins (M(r) 45,000 and 33,000 respectively). No difference in proliferation rates in vitro or in tumorigenic potential in nude mice were observed between mutant p53 clones or control cell lines. In contrast, a wild-type p53 clone (X833.W2) exhibited a significantly reduced tumorigenic potential in nude mice, whereas its in vitro proliferation rate was comparable to parental Hut292DM cells. The data indicate that exogenous expression of wild-type p53 is incompatible with Hut292DM lung cancer cell proliferation in vitro and suggest that p53-mediated growth control in vitro and in vivo may be dissociated and exerted by separate domains of the p53 protein.
Animals↗
Chloroplast DNA inversions and the origin of the grass family (Poaceae).
The phylogenetic affinities of the grass family (Poaceae) have long been debated. The chloroplast genomes of at least some grasses have been known to possess three inversions relative to the typical gene arrangement found in most flowering plants. We have surveyed for the presence of these inversions in grasses and other monocots by polymerase chain reaction amplification with primers constructed from sequences flanking the inversion end points. Amplification phenotypes diagnostic for the largest inversion (28 kilobase pairs) were found in genera representing all grass subfamilies, and in the nongrass families Restionaceae, Ecdeiocoleaceae, and Joinvilleaceae, but not in any other monocots--notably, Flagellariaceae, Anarthriaceae, Cyperaceae, or Juncaceae. This finding is consistent with one of the two principal views of grass phylogeny in suggesting that Poaceae and Cyperaceae (sedges) are not closest relatives. A second (approximately 6 kilobases) inversion appears to occur in a subset of the families possessing the 28-kilobase inversion and links Joinvilleaceae and Poaceae, while the smallest inversion appears unique to grasses. These inversions thus provide a nested set of phylogenetic characters, indicating a hierarchy of relationships in the grasses and allies, with Joinvilleaceae identified as the likely sister group to the Poaceae.
Base Sequence↗
The coding sequence of the hemolytically inactive C4A6 allotype of human complement component C4 reveals that a single arginine to tryptophan substitution at beta-chain residue 458 is the likely cause of the defect.
The C4A6 allotype of the human complement component C4 is known to be defective in C5 binding within the C5 convertase. To characterize the position and nature of the molecular defect in the C4A6 allotype we have isolated the C4A6 gene from a cosmid genomic DNA library. Direct sequencing of a 4.4-kb region of the gene covering exons 17 to 31 and encoding the C4d fragment and most of the rest of the alpha chain of C4 revealed that the C4A6 allele encodes the A isotypic residues Pro Cys-Leu Asp at positions 1101, 1102, 1105, and 1106 and the same residues as the C4A3 alpha gene at the polymorphic positions 1054 (Asp), 1157 (Asn), 1182 (Thr), 1188 (Val), 1191 (Leu) and 1267 (Ala). In addition the C4A6 allele was shown to encode a Pro at the previously characterized polymorphic position 707 in the C4a peptide where the C4A3 alpha allele encodes a Leu. The remaining 26 exons of the C4A6 gene were analyzed by detecting nucleotide mismatches in C4A6/C4A3 and C4A6/C4B1 DNA heteroduplexes using the chemical cleavage of mismatch technique. The regions around detected mismatches were sequenced. In total seven nucleotide differences were defined on comparison of the C4A6 and other C4 sequences, of which three were present in exons. Two of these resulted in amino acid changes. One of the amino acid differences is a known polymorphism in C4, a Tyr/Ser substitution at position 328 in the beta-chain. The second amino acid difference caused by a C to T transition in the first base of the codon for amino acid residue 458 was the only one shown to be specific to the C4A6 allotype. The C4A6 allotype contains a Trp residue at this position in the beta-chain instead of the Arg residue found in all other C4A and C4B allotypes so far characterized. We propose that this Arg to Trp substitution at beta-chain residue 458 is responsible for the inability of C4A6 to bind C5 in the C5 convertase.
Alleles↗
A single arginine to tryptophan interchange at beta-chain residue 458 of human complement component C4 accounts for the defect in classical pathway C5 convertase activity of allotype C4A6. Implications for the location of a C5 binding site in C4.
In general, C4A allotypes of human C4 show one-fourth to one-third the hemolytic activity of C4B allotypes. An exception to this rule is C4A6 which is almost totally deficient in hemolytic activity. Previous studies have localized the defect in C4A6 to the C5 convertase stage. Of the two critical events required for C5 cleavage, namely formation of a covalent adduct between C3b and the C4b subunit of the C3 convertase (C4b2a), and binding of C5 to this C4b-C3b complex, it is a defect in the latter step that accounts for the aberrant activity of C4A6. DNA sequencing studies described in a companion paper have suggested that the sole C4A6-specific difference was a Trp for Arg replacement at beta-chain residue 458. To directly ascertain whether this single substitution was responsible for the hemolytic defect in C4A6, we have used site-directed mutagenesis to introduce this change into both C4A and C4B cDNA expression plasmids. We found that the R to W replacement totally abrogated hemolytic activity. However, irrespective of the amino acid at residue 458, the mutant proteins behaved like their wild-type counterparts with respect to covalent binding to C1-bearing targets, i.e., the C4B recombinants displayed higher binding to sheep and human red cells than did the C4A counterparts. Furthermore, the mutants were able to form covalent C4b-C3b adducts. There was, however, substantially less C5 cleavage produced by cell-bound C4boxy23b complexes made with R458W mutant C4B than with wild-type C4B. These results are consistent with the sole defect in the mutants being at the C5 binding stage and strongly suggest that Arg 458 of the C4 beta-chain contributes to the C5 binding site of the molecule.
Complement C1↗
Increases in pericellular proteolysis at developing neuromuscular junctions in culture.
To determine whether localized changes in pericellular proteolysis contribute to synapse formation, we examined the degradative actions of developing Xenopus laevis nerve and muscle cells on films of extracellular matrix proteins adsorbed to the glass surface of a tissue culture chamber. Skeletal myocytes, growing neurites, and fibroblasts all removed fluorescent fibronectin and laminin from the culture substratum at regions of close cell-surface contact. In addition, however, motor neurites also displayed a particularly enhanced rate of gelatin elimination at developing neuromuscular junctions. It has already been shown (a) that there is a similar remodeling of organized muscle basal lamina proteoglycan accumulations along the path of nerve-muscle contact and (b) that this is the earliest detectable biochemical change specific to developing neuromuscular junctions. Our observations thus suggest that the establishment of motoneuron-muscle contact leads to a further activation of pericellular proteinases along both the pre- and the postsynaptic surfaces of the developing junction. We therefore consider whether site-specific proteinase-activation cascades could contribute to the inductive signals that direct synaptic differentiation.
Animals↗
Semen quality and endocrine parameters after acute testicular torsion.
Of 16 postpubertal patients evaluated following testicular torsion 9 were treated with detorsion and bilateral orchiopexy (detorsion group), and 7 were treated with ipsilateral orchiectomy and contralateral orchiopexy (orchiectomy group). Each patient was evaluated with regard to semen quality, endocrine parameters (follicle-stimulating hormone, luteinizing hormone and testosterone) and the presence or absence of semen antisperm antibodies. These data were compared to similar data from a group of proved fertile semen donors. The semen quality in the detorsion group did not differ significantly from that of controls (p = 0.25) but follicle-stimulating hormone was significantly elevated compared with that of controls before and after stimulation with gonadotropin-releasing hormone. The orchiectomy group, which had been subjected to prolonged torsion (mean 69 hours), demonstrated a significant decrease in semen quality compared with semen quality in controls (p = 0.001), with average sperm density of only 29.0 million per ml. Baseline and post-stimulation levels of follicle-stimulating hormone in the orchiectomy group were also significantly abnormal when compared with those in controls and in the detorsion group. Our study demonstrates that testicular damage (changes in semen quality and/or endocrine parameters) occurs in the ipsilateral and contralateral testis following torsion, regardless of treatment modality. However, with early intervention by detorsion and testicular salvage, subsequent semen quality is likely to remain within normal limits. Late surgical intervention, even with removal of the nonviable testes, may result in significant impairment of semen quality.
Acute Disease↗
Compressive mechanical properties of human cancellous bone after gamma irradiation.
The effect of gamma irradiation on the mechanical properties of human bone was examined. Specimens of cancellous bone were cut from the proximal epiphyseal region of fresh-frozen tibiae and divided into control and irradiated groups according to anatomical region. The irradiated groups were exposed to 10,000, 31,000, 51,000, or 60,000 gray (1.0, 3.1, 5.1, or 6.0 megarad). The specimens were tested in compression to failure to determine failure stress, strain to failure, and elastic modulus. Failure stress and elastic modulus were found to be proportional to the square of the density and were normalized with respect to this property. Significant differences in normalized failure stress (p less than 0.001) and normalized elastic modulus (p = 0.003), when compared with the values for matched control specimens, were found only for the specimens that had been irradiated with 60,000 gray (6.0 megarad).
Aged↗
Synaptic differentiation can be evoked by polymer microbeads that mimic localized pericellular proteolysis by removing proteins from adjacent surfaces.
Synaptic differentiation is normally "induced" by regulatory signals that are exchanged only at close contacts between neurites and their predetermined target cells. These signals can, however, be mimicked by contact of either cell with some kinds of polymer microbeads. To find what bead action is responsible for this mimicry, we compared the effects of active and inert microbeads on Xenopus muscle cells developing in culture and on glass-adsorbed films of laminin or fibronectin. Our results show that inductive bioactivity is a property of native polystyrene microbeads that (a) is not dependent merely on bead-muscle adhesion, (b) can be eliminated simply by exposing the beads to inert serum proteins, and (c) correlates closely with the ability of some beads to desorb proteins from adjacent surfaces. Quasi-synaptic differentiation of the muscle surface thus seems to be triggered by the focal removal of peripheral cell surface components, rather than by direct bead interactions with membrane receptors or ion channels or their gradual acquisition of endogenous regulatory substances. Since nerve-muscle interaction also causes an elimination of extracellular matrix proteins from the muscle surface, very early in synapse development, we consider the possibility that the extracellular degradation of peripheral surface components contributes to the transmission of inductive positional signals during synaptogenesis.
Animals↗
A note on Aeromonas spp. from chickens as possible food-borne pathogens.
The possible role of Aeromonas spp. as potential food-borne psychrotrophic pathogens was investigated by examining organisms isolated from processed raw chicken for their biochemical characteristics, ability to produce exotoxins and to grow at chill temperatures. These strains, in particular A. sobria, with identical characteristics to human diarrhoea-associated aeromonads were readily found. Chicken, and human and environmental (water) strains characterized in a previous study, were investigated for their ability to grow at refrigeration temperatures (5 +/- 2 degrees C) and, for selected strains, the theoretical minimum temperature for growth (Tmin) was determined from the growth pattern in a temperature gradient incubator. All enterotoxigenic chicken strains tested were typical mesophiles, with an optimal growth temperature of approximately 37 degrees C and Tmin values approximately 4.5 degrees C. They were rapidly outgrown by a psychrotrophic Pseudomonas sp. typical of spoilage biota found on food. Enterotoxin was not produced below 15 degrees C by any of the toxigenic food strains tested. The Aeromonas strains isolated from chickens in this study seem unlikely therefore to be a significant health risk, provided the chickens are properly stored and cooked. This would appear to be substantiated by the lack of reports of food-associated outbreaks of illness from these sources.
Aeromonas↗
Ten-year survival of patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation.
We evaluated the 10- to 15-year outcome of 252 patients with small-cell lung cancer entered into therapeutic clinical trials with or without chest and cranial irradiation. Thirty-two patients (13%) survived free of cancer for 2 or more years. Twelve patients (5%) survived at least 10 years free of cancer, and 10 patients are currently alive and free of cancer beyond 10 years. Six of these 10 patients currently function at a level comparable with that before diagnosis. The other 22 patients who were cancer-free at 2 years have died. Nine patients died from recurrent small-cell lung cancer 2 to 6.2 years after initiation of chemotherapy. Five died from non-small-cell lung cancer, three died of other malignancies, and five died of causes other than cancer. A small fraction of patients with small-cell lung cancer are cured of their original malignancy, but these patients remain at high risk for second cancers and death from other causes.
Actuarial Analysis↗
Outcome of patients with small-cell lung cancer: effect of changes in staging procedures and imaging technology on prognostic factors over 14 years.
In a study of 411 patients with small-cell lung cancer (SCLC) entered on therapeutic clinical trials between 1973 and 1987, we analyzed whether changes in the prognostic importance of pretreatment factors had occurred during the 14-year time period. After adjusting for other prognostic factors, brain involvement was associated with shorter survival in patients treated before December 1979 (P = .024) but not in patients treated thereafter (P = .54). The patients diagnosed before 1979 had brain metastases documented by radionuclide scan while computed cranial tomography (CCT) was more commonly used after 1979. Patients who had brain metastases diagnosed by radionuclide scan lived a shorter period of time than patients who had the diagnosis made by the more sensitive CCT scan (P = .031). In contrast, Cox proportional hazards modeling showed that liver metastases in patients were associated with shorter survival in patients treated after 1979 (P = .0007) but not in patients treated before then (P = .30). A larger proportion of patients had a routine liver biopsy before 1979 than after 1979 when more patients had the liver staged with less sensitive imaging studies and biochemical parameters. Patients with SCLC whose cancer was confined to the thorax but had medical or anatomic contraindications to intensive chest radiotherapy had similar survival compared with patients with limited-stage SCLC who were treated with combination chemotherapy alone (P = .68). From these data we conclude: (1) the sensitivity of the staging procedures used can affect the impact on survival of cancer involvement of a given site; and (2) patients with cancer confined to their chest with medical or anatomic contraindications to chest radiotherapy do not have a shorter survival than patients with limited-stage disease treated with chemotherapy alone.
Adult↗
Induction of a specialized muscle basal lamina at chimaeric synapses in culture.
To identify mechanisms that regulate the formation of the neuromuscular junction, we examined the cellular origin of a heparan sulfate proteoglycan (HSPG) that becomes highly concentrated within the synaptic cleft during the initial deposition of the junctional basal lamina. Using cultured nerve and muscle cells from anuran and urodele embryos, we prepared species-chimaeric synapses that displayed spontaneous cholinergic potentials, and eventually developed organized accumulations of acetylcholine receptors and HSPG at the sites of nerve-muscle contact. To determine the cellular origin of synaptic HSPG molecules, these chimaeric junctions were stained with both species-specific and cross-reactive monoclonal antibodies, labeled with contrasting fluorochromes. Our results demonstrate that synaptic HSPG is derived almost exclusively from muscle. Since it has already been shown that muscle cells can assemble virtually all of the known constituents of the junctional basal lamina into organized surface accumulations, without any input from nerve cells, we consider the possibility that the specialized synaptic basal lamina may be generated primarily by the myofibre, in response to another 'inductive' positional signal at the site of nerve-muscle contact.
Ambystoma mexicanum↗
Human parvovirus infection in children and severe anaemia seen in an area endemic for malaria.
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Adolescent↗
Correction of severe heparin-associated thrombocytopenia with intravenous immunoglobulin.
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Female↗
Suppression of tumorigenicity in human cell hybrids derived from cell lines expressing different activated ras oncogenes.
Four different human tissue-derived cell lines, each previously shown to express either a Ha-, Ki-, or N-ras-activated oncogene, were fused in four different paired combinations. The three combinations that involved the tumor line HT1080 (activated N-ras oncogene) were found to be tumorigenic in nude mice, but to different degrees. However, the fusion of the tumor lines EJ and SW480 (activated Ha-ras and Ki-ras, respectively) resulted in hybrid cells suppressed for tumorigenicity. The EJ x SW480 hybrids were found to harbor and express both of the activated ras oncogenes. The results suggest that tumorigenic suppression can occur in the presence of two transforming oncogenes of the ras family and that tumorigenicity associated with ras oncogene activation involves additional mechanisms that may differ among tumor cells.
Animals↗