Cystathionine in the brains of tree shrews and other mammals

The amino acid cystathionine is reported to show higher concentrations in the brains of man as compared to those of other species. Two-dimensional separation by electrophoresis-chromatography and densitometric analysis of amino acids showed that the brains of tree shrews had levels of cystathionine intermediate between those of man and other mammals such as tamarins, hedgehogs, and rats. Cystathionine may be involved in the circadian rhythms ofTupaiidae. In man a 10 fold variation in cerebral cystathionine is related to pathological conditions. Greater concentrations in white matter as compared to grey matter and other regional differences in brain tissue support the findings from inherited disorders that cystathionine plays an important role in the normal as well as the abnormal functioning of the brain.     

Influenza viruses: transmission between species

The only direct evidence for transmission of influenza viruses between species comes from studies on swine influenza viruses. Antigenically and genetically identical Hsw1N1 influenza viruses were isolated from pigs and man on the same farm in Wisconsin, U.S.A. The isolation of H3N2 influenza viruses from a wide range of lower animals and birds suggests that influenza viruses of man can spread to the lower orders. Under some conditions the H3N2 viruses can persist for a number of years in some species. The isolation, from aquatic birds, of a large number of influenza A viruses that possess surface proteins antigenically similar to the viruses isolated from man, pigs and horses provides indirect evidence for inter-species transmission. There is now a considerable body of evidence which suggests that influenza viruses of lower animals and birds may play a role in the origin of some of the pandemic strains of influenza A viruses. There is no direct evidence that the influenza viruses in aquatic birds are transmitted to man, but they may serve as a genetic pool from which some genes may be introduced into humans by recombination. Preliminary evidence suggests that the molecular basis of host range and virulence may be related to the RNA segments coding for one of the polymerase proteins (P3) and for the nucleoprotein (NP).     

On the Evolutionary Foundations of Language

New data on the cognitive capacities of other primates requires a reevaluation of our position on the nature of human language and the factors that led to its development. Pressures on the limited display system of the social primates may have made changes in the vocal tract anatomy of man associated with the development of upright posture of great selective importance. Human vocal tract anatomy may be at least as important as brain capacity in accounting for the origins of human language. An apparent upper age limit on efficient language acquisition in man leads to the "foreign accent" phenomenon. This may have been adoptively significant as a device which helped in the maintenance of a population structure in which rapid genetic change was possible. Embedding in language may represent a cognitive ability that is also reflected in the capacity for cultural variation, and may be extremely important in maintaining efficient population structure and in selecting for increasing intelligence.     

Participation of cGMP in realizing the effect of cholecystokinin-pancreozymin on the bile-excreting function of the human liver

The paper concerns studying the participation of cyclic nucleotides in the mechanisms of action of cholecystokinin on gallbladder function in man. Cyclic nucleosides (cAMP and cGMP) were identified by radioimmunoassay in the duodenal contents obtained from men in response to intravenous injection of cholecystokinin. The data obtained suggest that the action of cholecystokinin on gallbladder function in man is mediated via cGMP, whereas cAMP is not implicated in the effect of of cholecystokinin on gallbladder function in man. Disturbances in cyclic nucleotide systems may be viewed in the light of the evidence obtained as a possible pathogenetic factor in the development of gallbladder dyskinesia.     

Under what circumstances is the human XY bivalent tangled? A note on chromosomally-derived sterility

A microspread, early-mid diplotene nucleus of a man with a normal karyotype and presumably normal meiosis is compared with a similar, earlier described nucleus of a man with meiotic arrest, heterozygous for a (14;21) Robertsonian translocation (Rosenmann et al., 1985). The axes of the XY bivalent of normal diplotene have an extremely tangled configuration, whereas those of the meiotically-arrested cell are straight, recalling the shape of the XY which is normally found in early pachytene. The morphological reversal from the complex configuration to a simpler shape may be associated with reactivation of the sex chromosome(s). Such a reactivation may be responsible for the sterility of the carrier of the Robertsonian translocation which thus may be considered as chromosomally-derived. The diplotene cells shown here have autosomal bivalents with continuous axes and various degrees of focal separation as is typical for diplotene in general. The observations on axis continuity, bivalent segmental dilatations, and XY tanglement in diplotene are compared with findings by others in human ultrathin sectioned material.     

Maturation process of secondary ossification centers in the rat and assessment of bone age.

The maturation process from the appearance to the fusion of the secondary ossification centers of extremities was studied in Wistar rats aged 0 to 134 weeks. The examination of the secondary ossification centers made by radiography. The assessment of the stage of development was made in accordance with the criteria proposed by Ohwada and Sutow. The secondary ossification center was found to be take one of the following three types of maturation processes : (1) the acute ossification, (2) the delayed ossification, and (3) the incomplete ossification. No fusion was observed up to 134 weeks in certain epiphyses of the rat. This type of ossification designated as the incomplete ossification may be specific to the mouse and rat. The relative lengths of time required for appearance and fusion in the average prospective life were obtained for the rat. They were compared with those of the mouse and man. The relative length of time necessary for maturity of the secondary ossification centers was shown to be the shortest in the rat and the longest in man. The results suggested that the rat may reach maturity in the bone age at 17 to 21 weeks of age. The rat at this age may be regarded as being adult corresponding to age 17 weeks in mice and 18 to 24 years in man.     

Dental destruction in Broken-Hill man

The determination of the type of Broken-Hill man's diet by the study wear on occlusal surfaces may be complemented by the examination of striations left by the diet on the dental crown. Microscopic grooves of dental buccal surfaces yields new data as to what prehistoric man ate. It is suggested that Broken-Hill man allowed the development of rampant caries through his ignorance of the use of tooth picks.     

台湾海峡晚更新世人类肱骨化石

产自台湾海峡海底的人类右肱骨石化程度高; 个体大而粗壮 ,三角肌粗隆发育 ,骨干上下两半段不在同一纵轴上 ,形成 6 5°的夹角 ,这些显示不同于新石器时代和现代人的原始性状 ,其演化水平和日本的港川人及欧洲的克罗马农人相当。与人化石一同捞出的哺乳动物化石有古菱齿象、野马、最后鬣狗、达氏四不像鹿等 ,表明其时代为晚更新世晚期。     

Sequence of ossification of the foot in marmosets (Saguinus oedipus)

The cleared and alizarin-stained feet of eight marmoset (Saguinus oedipus) fetuses revealed a sequence of initial ossification of the 19 bones of the foot that is almost totally different from that of man. The most striking difference is in the order of ossification of the distal phalanx of the big toe; in man it is the first bone to commence ossification, in the marmoset it is the fourteenth. It is suggested that the sequence of initial ossification in the foot may be species specific among the primates and may serve as a useful marker of teratogenic action.     

ATP-sensitive K+ channels in human isolated pancreatic B-cells

Glucose-stimulated insulin release from rodent pancreatic B-cells is thought to be initiated by the closing of ATP-sensitive K+ channels in the plasma membrane as a consequence of glucose metabolism. We have identified an ATP-sensitive K+ channel in membrane patches excised from human B-cells which is similar to that found in rodent B-cells in conductance, kinetics, ATP sensitivity and its inhibition by sulphonylureas. In man, the ATP-sensitive K+ channel may also have a central role in glucose-stimulated insulin secretion and may be (linked to) the receptor for the hypoglycemic sulphonylureas.     

Class II genes of miniature swine. IV. Characterization and expression of two allelic class II DQB cDNA clones

Two cDNA clones coding for allelic miniature swine MHC class II Ag DQB chains have been isolated, characterized, and shown to be expressed after transfection into mouse fibroblasts. The two alleles differ at the nucleotide level by an overwhelming proportion of replacement substitutions, suggesting the influence of selection for polymorphism. Most of the resulting predicted amino acid replacements are in regions commonly polymorphic in mouse Ab and human DQB sequences, corresponding to the predicted Ag recognition site. Nucleotide and amino acid sequence comparisons to homologous mouse and human sequences show more similarity between swine and man than between either swine and mouse or man and mouse. This tendency is most pronounced when comparing the 3' untranslated regions. However, an examination of unique cross-species sharing of amino acid residues suggests a closer relationship between both man and miniature swine and man and mouse than between miniature swine and mouse. The simplest explanation we can envision for these findings is that the mouse DQB gene homologue (Ab) has been subject to a higher substitution rate than either swine or human DQB genes. An additional cytoplasmic exon expressed in mouse Ab gene products and in putative human DQB2 gene products is lacking in both swine and human DQB cDNA clones. Its absence suggests either that the expression of this exon in mouse Ab genes was activated after mammalian speciation or that the expression of this exon was independently inactivated in swine DQB and human DQB1 genes. Alternatively, the mouse Ab gene may be derived from the same primordial gene as human DQB2, whereas the pig DQB gene may be derived from the same primordial gene as the human DQB1 gene.     

Plants,insects, and man—their interrelationships

Plants constitute a vast cornucopia of chemical substances used for defense from attack by insects. These may be classified as insect attractants, repellents, toxicants, inhibitors of growth and development, sterilants, and feeding deterrents. An overview of the subject and its interrelationships with man is presented.     

Evaluation of mutagenicity and carcinogenicity using three-tier system

A three-tier approach to mutagenicity evaluation has previously been proposed [1] with three underlying general principles. (1) No generally mutagenic chemical should be released into the environment or be permitted to be used if there exists a satisfactory non-mutagenic substitute; (2) the extent and rigour of the screening procedures should be related to the extent to which man is, or is likely to be exposed to the agent; (3) a mutagenic substance may be used if the benefits are judged to be great enough to outweigh the hazards and if appropriate controls are exercised. The first tier contains short-term screening tests with sub-mammalian systems, the second tier contains short- and longer-term tests with whole mammals, and the third tier involves a risk-benefit evaluation which may entail further more specialized testing procedures and experiments on the detailed metabolism of the agent in vivo.Such a scheme may in principle be used wherever there exists a long-term hazard for which short-term predicitive tests exist. Carcinogenicity evaluation fits well into a three tier approach and evaluation for carcinogenicity and mutagenicity may be run in parallel with some degree of overlap [2]. Long term carcinogenicity trials fall into tier 2, for example, while tier 1 may include (in addition to mutagenicity) such tests as degranulation of endoplasmic reticulum [3] induction of biphenyl hydroxylase [4] and transformation of cells to malignancy in vitro.The third tier of risk-benefit evaluation involves the determination of risk. This is almost impossible to do in a quantitative manner at the present time. Nevertheless some guidance must be given to the decision-maker, however approximate and surrounded by reservations it may be. One approach is to use the radiation-equivalent dose concept using data from a system that is as closely related as possible to man [1]. Such a result may have some validity for the particular end-point and dose range used. Other end-points and dose ranges may give a different value for radiation equivalence and the weight given to it must be determined by the likely importance of the end-point in constituting a genetic hazard to man. The radiation-equivalent dose is thus a common unit of convenience for chemical mutagens which also has the advantage of being more readily understood by regulators and decision-makers without a genetic background. An example of a tentative and qualified radiation-equivalent calculation has been carried out for the fungicide captan [5]. The use of radiation-equivalent concept by Committee 17 [6] seems to imply a near constancy of radiation equivalent dose values over a wide range of species and end-points. This extensio of the radiation-equivalent concept from its use as an approximate common unit of effect to a philosophy for making extrapolations between widely different species does not seem to be justified at the present time.     

Well man clinic in general practice.

The establishment of a well man clinic run entirely by a nurse in general practice showed an appreciable number of men to be hypertensive, smokers, or overweight; it also showed some previously undetected disease. Efforts were made either to treat or to counsel men in whom these findings were made. A well man clinic may have greater value than a well woman clinic.     

Unexpected evidence for active brown adipose tissue in adult humans

The contention that brown adipose tissue is absent in adult man has meant that processes attributed to active brown adipose tissue in experimental animals (mainly rodents), i.e., classical nonshivering thermogenesis, adaptive adrenergic thermogenesis, diet-induced thermogenesis, and antiobesity, should be either absent or attributed to alternative (unknown) mechanisms in man. However, serendipidously, as a consequence of the use of fluorodeoxyglucose positron emission tomography (FDG PET) to trace tumor metastasis, observations that may change that notion have recently been made. These tomography scans have visualized symmetrical areas of increased tracer uptake in the upper parts of the human body; these areas of uptake correspond to brown adipose tissue. We examine here the published observations from a viewpoint of human physiology. The human depots are somewhat differently located from those in rodents, the main depots being found in the supraclavicular and the neck regions with some additional paravertebral, mediastinal, para-aortic, and suprarenal localizations (but no interscapular). Brown adipose tissue activity in man is acutely cold induced and is stimulated via the sympathetic nervous system. The prevalence of active brown adipose tissue in normal adult man can be only indirectly estimated, but it would seem that the prevalence of active brown adipose tissue in the population may be at least in the range of some tens of percent. We conclude that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.     

Recommendations for testing new chelating agents for removal of incorporated actinides from the body

Summary The body content of certain radionuclides and the consequences of accidental incorporation may be reduced by treatment with chelating agents. Such agents have been widely studied and have proved to be useful in man. Chelation therapy may also be advantageous in certain cases of heavy metal poisoning. There is still a need to develop new, more efficient and less toxic agents and better therapeutic schedules for using the existing agents. So far as possible the testing of potential new compounds should be carried out using standardized methods.Supported by the Radiation Protection Programme of the Commission of the European Communities-publication no 1889     

Oxidants and the pathophysiology of burn and smoke inhalation injury.

A skin burn is a common traumatic injury that results in both local tissue damage and a systemic mediator-induced response. There is evidence of both local and systemic oxidant changes manifested by lipid peroxidation in animal burn models and also in burned man. Both increased xanthine oxidase and neutrophil activation appear to be the oxidant sources. Animal studies have also demonstrated decreased burn edema, and also decreased distant organ dysfunction with the use of antioxidants, suggesting a cause-and-effect relationship, which needs to be tested in man. Smoke inhalation injury, a chemical injury to the airways caused by incomplete products of combustion, is frequently seen in conjunction with a body burn. Lipid peroxidation, both in lung and in distant organs, is also seen with this injury. The combined body burn and smoke inhalation injury lead to a marked increase in mortality rate and also an increase in the degree of generalized oxidant release and lipid peroxidation. Although data in man are limited, the available information, along with that from animal research on burns and smoke inhalation, indicates oxidants may well play a key role, and antioxidants may be of clinical therapeutic use.     

Frequency and coverage of trinucleotide repeats in eukaryotes

In the aim to assess whether the tri-repeat shortage reported in vertebrates affects specific motifs, such as those causing neuromuscular diseases in man, we detected approximate di-, tri- and tetra-repeats (STR) longer than 25 bases in human chromosomes 21 and 22, and in some model organisms (M. musculus, D. melanogaster, C. elegans, A. thaliana and S. cerevisiae). We found that overall STR are more represented in mouse and in man than in the other organisms. However, tri-repeats are less represented than di- and tetra- in man and mouse, but show intermediate values between di- and tetra- in the other organisms. In man, ACG shows the lowest both frequency and coverage, ATC the highest coverage and AAT the highest frequency. In general, coverage and frequency of tri-repeats are linearly related, except for ACC, ATC, AAG, AGG motifs in man and AAG, AGG in mouse, which exhibit unexpectedly long repeats. Often their copy numbers exceed that found responsible for the dynamic mutations, set at around 40. The shortage in frequency and coverage of tri- vs. di- and tetra-repeats observed in man and mouse can be ascribed to a subset of the remaining tri-repeat motifs, but among them those recognized as dynamically mutable (AAG, AGC and CCG) are not the least represented. Possible constraints in tri-repeat expansion seem to be structural and conserved along the evolutionary scale: a motif-specific relaxation of the relevant controls may be responsible for the occasional expansions found in mouse and man.     

Myopathies caused by three mutations of the mouse

Our studies indicate that comparison of the three hereditary myopathies in mice, dy and dy2J, and myd, may provide clues for the fact that "muscular dystrophy" of man defines a group of disorders having both similar and individual characteristics. We have previously suggested that multiple or pleiotropic gene effects as well as interaction of genes may occur not only in mice but also in man. In addition, more than one gene may control or influence pathways of muscle metabolism.