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Since the Middle Ages, European society has passed through two successive stages in the "civilizing process." Each has been attended by profound changes in psychological and social codes. These are examined in relation to a greater concern with health and hygiene in response to four waves of epidemics: leprosy, plague, syphilis, and cholera. Speculations are offered about AIDS and the "civilizing process".
Sera from 10 patients with AIDP and 10 age-matched controls were microinjected into the tibial division of rat sciatic nerve using improved microinjection techniques and coded sera. No statistically significant changes in conduction velocity or amplitude of the compound muscle action potential (CMAP) or in the monophasic compound action potential (CAP) parameters was found at 1 week. In nerves studied with serial recording over 1 h a small but significantly greater reduction in CMAP amplitude was observed at 60 min in the AIDP group and at both 30 and 60 min when only sera from very severely affected (bed-ridden) patients were considered. A similar reduction was found following microinjection into focally demyelinated nerves. The finding of a small reduction in CMAP amplitude in the first hour suggests the presence in some AIDP patients of serum blocking or demyelinating factors but the clinical significance of this small reduction is uncertain.
Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. In humans, MH is inherited in an autosomal dominant fashion; in swine, the principal model for MH, it is in a recessive fashion. Those with MH susceptibility usually are asymptomatic except in the presence of certain "triggering" anaesthetic agents such as isoflurane, enflurane and the muscle relaxant succinylcholine. Upon such exposure hypermetabolism, increased CO2 production, acidosis, muscle rigidity, rhabdomyolysis and hyperthermia occur. Untreated, death may result in 70% of patients. With prompt diagnosis and treatment with dantrolene sodium, the mortality is less than 10%. The overall incidence of MH is low (perhaps 1:50,000 anaesthetics), but it is more common in children. Children also display a paradoxical increase in jaw muscle tone to succinylcholine which often presages MH, but confusing clinically, may also be a normal response to succinylcholine. The pathophysiology of MH centres around a defect in calcium flux in skeletal muscle. A specific base pair change in the gene that codes for the ryanodine receptor calcium channel in muscle has been demonstrated in susceptible swine, but occurs rarely in humans. It is hoped that the understanding of the molecular genetics of MH will lead to a simpler diagnostic test than is currently available, and enhance our understanding of MH and its relation to other myopathies.
Hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP) are inherited disorders of erythrocyte shape that are frequently associated with abnormalities in alpha-spectrin, one of the principal structural proteins of the erythrocyte membrane skeleton. Five polymorphisms of the alpha-spectrin gene, located in a 6-kb interval of genomic DNA, were identified and analyzed in normal and mutant alpha-spectrin alleles. Three of these polymorphisms are due to single nucleotide substitutions in the alpha-spectrin gene coding region that lead to changes in the amino acid sequence. In combination, these three polymorphisms are responsible for the different peptide phenotypes of the alphaII domain previously observed following limited tryptic digestion of spectrin protein. The most common haplotype, type 1, was found predominantly in Caucasians and was the only haplotype identified in Asians. Haplotypes 2, 3, and 4 were identified predominantly in individuals of African ancestry and were commonly found in patients with HE or HPP. Analysis of coinheritance of alphaII domain polymorphisms with alpha-spectrin gene mutations causing HE or HPP in African-American patients with HE and HPP suggests that, with one exception, a given HE/HPP mutation is present in an alpha-spectrin gene of only one haplotype, indicating a founder effect. The other two polymorphisms located in this region of the alpha-spectrin gene do not change the amino acid sequence of the encoded alpha-spectrin chain and are not in linkage disequilibrium with three of the four alphaII domain haplotypes. A model is proposed for the evolutionary origin of the different haplotypes.
The third version of the Health Plan Employer Data and Information Set (HEDIS) has been revised for 1998. Many changes affect either the clinical codes that determine whether a member received a service or the content of the service being measured. The updated version contains 15 fewer measures than did its predecessor.
We have shown an association between a common mutation in the factor XIII a-subunit gene, coding for an amino acid change, 3 amino acids from the thrombin activation site (factor XIII Val34Leu) that may protect against myocardial infarction and predisposes to intracranial hemorrhage. To investigate the possible role of factor XIII Val34Leu in the pathogenesis of venous thromboembolism (VTE) and potential interactions with factor V Leiden (FV:Q506) and prothrombin G --> A 20210, we studied 221 patients with a history of VTE and 254 healthy controls. Patients with VTE showed an increased frequency of the FXIII Val/Val genotype (63% v 49%) and a lower frequency of the Val/Leu genotype (31% v 42%) than controls (P =. 007). FV:Q506 heterozygotes were more frequent in VTE patients (11%) than controls (5%; P =.04). The prothrombin G --> A 20210 mutation was present in only 3 patients and no controls (P =.10). In a logistic regression model for a history of VTE, the odds ratio (95% confidence interval) for FXIII Val/Leu or Leu/Leu genotype was 0.63 (0.38 to 0.82) and for possession of FV:Q506 2.40 (1.17 to 4.90). There was no evidence for an interaction between factor XIII Val34Leu genotype and FV:Q506, prothrombin G --> A 20210, sex, or age. It is concluded that possession of the Leu allele at factor XIII Val34Leu is protective against deep venous thrombosis.
Two types of cDNA encoding IgG1 heavy chain (gamma1) were isolated from a single domestic short-hair cat. Sequence analysis indicated a higher level of similarity of these Cgamma1 sequences to human Cgamma1 sequence (76.9 and 77.0%) than to mouse sequence (70.0 and 69.7%) at the nucleotide level. Predicted primary structures of both the feline Cgamma1 genes, designated as Cgamma1a and Cgamma1b, were similar to that of human Cgamma1 gene, for instance, as to the size of constant domains, the presence of six conserved cysteine residues involved in formation of the domain structure, and the location of a conserved N-linked glycosylation site. Sequence comparison between the two alleles showed that 7 out of 10 nucleotide differences were within the C(H)3 domain coding region, all leading to nonsynonymous changes in amino acid residues. Partial sequence analysis of genomic clones showed three nucleotide substitutions between the two Cgamma1 alleles in the intron between the CH2 and C(H)3 domain coding regions. In 12 domestic short-hair cats used in this study, the frequency of Cgamma1a allele (62.5%) was higher than that of the Cgamma1b allele (37.5%).
Anterior pituitary tumors arise sporadically, and also as part of the inherited multiple endocrine neoplasia type 1 (MEN 1) syndrome. To investigate the role of the recently isolated men1 gene in sporadic pituitary tumorigenesis, the complete coding sequence was screened for mutations in 45 sporadic anterior pituitary tumors, including 14 hormone-secreting tumors and 31 nonsecreting tumors, by dideoxy fingerprinting and sequence analysis. No pathogenic sequence changes were found in the men1 coding region. The men1 gene was expressed in 43 of these tumors with sufficient RNA, including one tumor with loss of heterozygosity (LOH) for several polymorphic markers on chromosomal region 11q13. Furthermore, both alleles were expressed in 19 tumors in which the constitutional DNA was heterozygous for intragenic polymorphisms. Thus, inactivation of the men1 tumor suppressor gene, by mutation or by imprinting, does not appear to play a prominent role in sporadic pituitary adenoma pathogenesis.
The entire nucleotide sequence for the coding regions of a Danish PMTV isolate 54-15 was determined and compared to other known and sequenced isolates of PMTV. Many nucleotide and amino acid changes were found in parts of RNA coding for the triple gene block (TGB) proteins and in the part of the RNA coding for the read-through region of the coat protein (CP). These regions for two other isolates, the mild one 54-10 and the severe one 54-19, were sequenced. Only two amino acid changes were found to correlate with the subdivision of isolates according to symptom development into mild and severe subgroups. In addition, the phylogenetic tree was obtained suggesting the closest relationship between isolates 54-15 and 54-10. Although the sequence comparisons indicate a high genetic stability of PMTV populations, a surprising change was found in the newly sequenced isolates--the replacement of the AUG start codon of the fourth gene of the TGB encoding RNA, coding for a cystein-rich protein, by the less efficient GUG start codon.
We have established high resolution methods for global monitoring of gene expression in Escherichia coli. Hybridization of radiolabeled cDNA to spot blots on nylon membranes was compared to hybridization of fluorescently-labeled cDNA to glass microarrays for efficiency and reproducibility. A complete set of PCR primers was created for all 4290 annotated open reading frames (ORFs) from the complete genome sequence of E.coli K-12 (MG1655). Glass- and nylon-based arrays of PCR products were prepared and used to assess global changes in gene expression. Full-length coding sequences for array printing were generated by two-step PCR amplification. In this study we measured changes in RNA levels after exposure to heat shock and following treatment with isopropyl-beta-D-thiogalactopyranoside (IPTG). Both radioactive and fluorescence-based methods showed comparable results. Treatment with IPTG resulted in high level induction of the lacZYA and melAB operons. Following heat shock treatment 119 genes were shown to have significantly altered expression levels, including 35 previously uncharacterized ORFs and most genes of the heat shock stimulon. Analysis of spot intensities from hybridization to replicate arrays identified sets of genes with signals consistently above background suggesting that at least 25% of genes were expressed at detectable levels during growth in rich media.
The Escherichia coli grpE gene (along with dnaK, dnaJ, groEL, and groES) was originally identified as one of the host factors required for phage lambda growth. The classical grpE280 mutation was the only grpE mutation that resulted from the initial screen and shown to specifically block the initiation of lambda DNA replication. Here we report the isolation of several new grpE missense mutations, again using phage lambda resistance as a selection. All mutants fall into two groups based on their temperature-dependent phenotype for lambda growth. Members of the first group (I), including grpE17 and grpE280, which was obtained again, are resistant to lambda growth at both 30 and 42 degrees C. Members of the second group (II), including grpE25, grpE66, grpE103, grpE13a, grpE57b, and grpE61, are sensitive to lambda growth at 30 degrees C but resistant at 42 degrees C. All mutations are recessive, since an E. coli grpE null mutant strain carrying these mutant alleles on low-copy-number plasmids are sensitive to infection by the lambda grpE+ transducing phage. Both group I and group II mutants are temperature sensitive for E. coli growth above 42 degrees C. The nucleotide changes were identified by sequencing analyses and shown to be dispersed throughout the latter 75% of the grpE coding region. Most of the amino acid changes occur at conserved residues, as judged by sequence comparisons between E. coli and other bacterial and yeast GrpE homologs. The isolation of these new mutations is the first step toward a structure-function analysis of the GrpE protein.
The role of aromatic amines in cancer inducing is mainly connected with their metabolism in the organism. During successive cell changes certain adducts are generated which may bind DNA. Their ability to cause mutations depends on whether a given adduct was generated with a free form or an acetylated amine. Adducts generated with non-acetylated amines are the main cause of mutations, i.e. changes of base in a DNA-coding triplet. Also, an important effect in cancerogenic activity of aromatic hydrocarbons is attributed to recently discovered oncogenes. Changes in oncogene expression may result in proliferations of the cells of the urinary bladder epithelium, which may induce their transformation into neoplastic cells. Diagnostic tests based mainly on cytological studies do not make it possible to detect early changes of the proliferation process in the cells of the urinary bladder epithelium. Only the recently introduced methods using monoclonal antibodies, which facilitate determination of oncogene protein products in organism's fluids, are sensitive indicators of initiating the neoplastic process in the urinary bladder.
The recording of posture has a long history in the study of ergonomics, but has generally been concerned with the assessment of mechanical strain on the human body. This paper extends the concern to the thermal implications of posture. A change in posture can change the effective body surface area available for heat exchange with the environment and therefore the metabolic rate per unit body surface area. This effect is systematised into a method of postural coding which reflects the extent of changes in effective body surface area available for heat exchange. The paper reports a brief assessment of the extent of the effect of posture in normal office work and the extent to which posture is temperature-related.
The sequential fulfillment of the principle of succession necessarily guides the main steps of the genetic code evolution to be reflected in its structure. The general scheme of the code series formation is proposed basing on the idea of "group coding" (Woese, 1970). The genetic code supposedly evolved by means of successive divergence of pra-ARS's loci, accompanied by increasing specification of recognition capacity of amino acids and triplets. The sense of codons had not been changed on any step of stochastic code evolution. The formulated rules for code series formation produce a code version, similar to the contemporary one. Based on these rules the scheme of pra-ARS's divergence is proposed resulting in the grouping of amino acids by their polarity and size. Later steps in the evolution of the genetic code were probably based on more detailed features of the amino acids (for example, on their functional similarities like their interchangeabilities in isofunctional proteins).
This final rule makes several changes affecting Medicare Part B payment. The changes include: implementation of resource-based malpractice insurance relative value units (RVUs); refinement of resource-based practice expense RVUs; payment for physician pathology and independent laboratory services; discontinuous anesthesia time; diagnostic tests; prostate screening; use of CPT modifier -25; qualifications for nurse practitioners; an increase in the work RVUs for pediatric services; adjustments to the practice expense RVUs for physician interpretation of Pap smears; and revisions to the work RVUs for new and revised CPT codes for calendar year 1999 and a number of other changes relating to coding and payment. Furthermore, we are finalizing the 1999 interim physician work RVUs and are issuing interim RVUs for new and revised codes for 2000. This final rule solicits public comments on the second 5-year refinement of work RVUs for services furnished beginning January 1, 2002 and requests public comments on potentially misvalued work RVUs for all services in the CY 2000 physician fee schedule. This final rule also conforms the regulations to existing law and policy regarding: removal of the x-ray as a prerequisite for chiropractic manipulation; the exclusion of payment for assisted suicide; and optometrist services. This final rule also announces the calendar year 2000 Medicare physician fee schedule conversion factor under the Medicare Supplementary Insurance (Part B) program as required by section 1848(d) of the Social Security Act. The 2000 Medicare physician fee schedule conversion factor is $36.6137.
The lexicon of illness terms used by Mexican American women is affected by the practice of speaking both Spanish and English and by the coexistence of several health systems. When there is changning participation in various health systems, with increasing interference and code switching, linguistic evidence for these changes may be found. In some cases an English disease name is borrowed. In others, a cognate is coined from an English disease name. Some terms, now no longer useful, are dropped. Finally, some Spanish disease names which do not have equivalents in English or in scientific medical theory may be retained, but there is a shift in the meaning of the words themselves. The direction of the shift is towards semantic correspondence with the concepts of scientific medicine. In these ways the medical lexicon is changed, with the changes reflecting a new medical culture.
Reaction-diffusion theory for pattern formation is considered in relation to processes of biological development in which there is continuous growth and shape change as each new pattern forms. This is particularly common in the plant kingdom, for both unicellular and multicellular organisms. In addition to the feedbacks in the chemical dynamics, there is then another loop linking size and shape changes with the reaction-diffusion patterning of growth controllers in the growing region. In studies by computation, the codes must incorporate, alongside the usual solvers of the partial differential dynamic equations, a versatile growth code, to express any kind of shape change. We have found that regulation of shape change in particular ways (e.g. to make narrow-angle branchings) demands new features in our chemical mechanisms. Our growth algorithm is for a surface growing tangentially, but moving outward and changing shape to accommodate the extra area. This is potentially applicable both to the tunica layer of multicellular plant meristems and to the growing tip of the cell surface, e.g. in the morphogenesis of single-celled chlorophyte algae which display branching processes: whorl formation in Acetabularia (Dasycladales) and repeated dichotomous branching in Micrasterias (Desmidiaceae). For computational studies, a hemispherical shell is a reasonable idealization of the initial shape. We describe results of two types of study: (1) Pattern formation by three reaction-diffusion models, with contrasted nonlinearities, on the hemispherical shell, particularly to find conditions for robust formation of annular pattern or pattern for dichotomous branching, both of which are common in plants. (2) Sequential dichotomous branchings in a system growing and changing in shape from the hemispherical start.
The viral component of Turnip mosaic virus (TuMV) determining virulence to the Brassica napus TuRB01 dominant resistance allele has been identified. Sequence comparisons of an infectious cDNA clone of the UK 1 isolate of TuMV (avirulent on TuRB01) and a spontaneous mutant capable of infecting plants possessing TuRB01 suggested that a single nucleotide change in the cylindrical inclusion (CI) protein coding region (gene) of the virus was responsible for the altered phenotype. A second spontaneous mutation involved a different change in the CI gene. The construction of chimeric genomes and subsequent inoculations to plant lines segregating for TuRB01 confirmed the involvement of the CI gene in this interaction. Site-directed mutagenesis of the viral coat protein (CP) gene at the ninth nucleotide was carried out to investigate its interaction with TuRB01. The identity of this nucleotide in the CP gene did not affect the outcome of the viral infection. Both mutations identified in the CI gene caused amino acid changes in the C terminal third of the protein, outside any of the conserved sequences reported to be associated with helicase or cell-to-cell transport activities. This is the first example of a potyvirus CI gene acting as a determinant for a genotype-specific resistance interaction.