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Box-Jenkins modeling of chronological series of twin births and single births.

A time-series analysis by Box-Jenkins modeling of the monthly observations of twin births and singleton births was attempted. The study is population based. The single-birth series has been matched to the twin-birth series for maternal birth cohort, parity of the twin birth, and residence of the parents. Three-hundred forty-one twin pairs and 340 singleton births were grouped into chronological series spanning 72 months of observation. Univariate and bivariate time-series analyses were used. Box-Jenkins modeling shows that both series share the same basic demographic and reproductive risk factors, such as ovulation and conception rates, abortions, sexual intercourse, and the less well-known random events that determine the time of delivery. These factors are randomly related to both birth processes but exert a more important influence on twin births. Beyond these crude features, twin- and single-birth series differ by the frequency of their seasonal cycle. Twin births show low-frequency variations because of a rather limited number of factors that impinge markedly on the twinning process. Single births are subjected to higher frequency variations that can be ascribed to a greater number of structuring factors, the action of which is less pervasive. Only the January peak is common to both types of births. Aside from the common features, the bivariate analysis shows that both series of births are independent, neither being related to the other. It is concluded that the subtle structuring of both processes is largely distinct. The large fraction of the unaccounted variation of each birth process (about 70%) suggests that most of the variation is due to as yet unidentified factors. The search for environmental and geocosmic factors at the origin of conception and confinement should be considered in future undertakings.

Birth Order

Proteinases and their inhibitors in cells and tissues.

A large body of evidence has been assembled to indicate the substantial importance of proteolytic processes in various physiological functions. It has recently become clear too that endo-acting peptide bond hydrolases provisionally characterized and classified at present as serine, cysteine, aspartic and metallo together with unknown catalytic mechanism proteinases sometimes act in cascades. They are controlled by natural proteinase inhibitors present in cells and body fluids. In the first part of the present monograph the author was concerned to present an overview on the morphological and physiological approach to localization, surveying reaction principles and methods suitable for visualization of proteolytic enzymes and their natural and synthetic inhibitors. In the second part the roles played by proteinases have been summarized from the point of view of cell biology. The selection of earlier and recent data reviewed on the involvement of proteolysis in the behavior of individual cells reveals that enzymes, whether they be exogeneous or intrinsic, can be effective and sensitive modulators of cellular growth and morphology. There exists a close correlation between malignant growth and degradation of cells. It appears likely that as yet unknown or at least so far inadequately characterized factors that influence the survival or the death of cells may turn out to be proteinases. The causal role of extracellular proteolysis in cancer cell metastases, in stopping cancer cell growth and in cytolysis remains for further investigated. Ovulation, fertilization and implantation are basic biological functions in which proteolytic enzymes play a key role. The emergence of new approaches in reproductive biology and a growing factual basis will inevitably necessitate a reevaluation of present knowledge of proteolytic processes involved. The molecular aspects of intracellular protein catabolism have been discussed in terms of the inhibition of lysosomal and/or non-lysosomal protein breakdown. Peptide and protein hormone biosynthesis and inactivation are still at the centre of interest in cell biology, and a number of proteinases have been implicated in both processes. A number of conjectures partly based on the author's own work have been discussed which suggest the possibility of the involvement of proteolysis in exocytosis and endocytosis. The author's optimistic conclusion is that through the common action of biochemists, cell biologists, cytochemists, and pharmacologists the mystery of cellular proteolysis is beginning to be solved.

Animals

A general model for the African trypanosomiases.

A general mathematical model of a vector-borne disease involving two vertebrate host species and one insect vector species is described. The model is easily extended to other situations involving more than two hosts and one vector species. The model, which was developed from the single-host model for malaria described by Aron & May (1982), is applied to the African trypanosomiases and allows for incubation and immune periods in the two host species and for variable efficiency of transmission of different trypanosome species from the vertebrates to the vectors and vice versa. Equations are derived for equilibrium disease prevalence in each of the species involved. Model predictions are examined by 3-dimensional phase-plane analysis, which is presented as a simple extension of the 2-dimensional phase-plane analysis of the malaria model. Parameter values appropriate for the African trypanosomiases are derived from the literature, and a typical West African village situation is considered, with 300 humans, 50 domestic animals and an average population of 5000 tsetse flies. The model predicts equilibrium prevalences of Trypanosoma vivax, T. congolense and T. brucei of 47.0, 45.8 and 28.7% respectively in the animal hosts, 24.2, 3.4 and 0.15% in the tsetse vectors, and a 7.0% infection of humans with human-infective T. brucei. The contribution to the basic rate of reproduction of the human-infective T. brucei is only 0.11 from the human hosts and 2.54 from the animal hosts, indicating that in the situation modelled human sleeping sickness cannot be maintained in the human hosts alone. The animal reservoir is therefore crucial in determining not only the continued occurrence of the disease in humans, but its prevalence in these hosts as well. The effect of changing average fly density on equilibrium disease prevalences is examined, together with the effect of seasonal changes in fly numbers on disease incidence. In a seasonal situation changes in fly mortality rates affect both future population size and infection rate. Peak disease incidence lags behind peak fly numbers, and that in the less favoured host lags behind that in the more favoured host. Near the threshold fly density for disease transmission disease incidence is more changeable than at higher fly densities and may even exceed equilibrium prevalence at the same average fly density (because most hosts are susceptible at the time that fly numbers begin their annual increase).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Perinatal mortality and morbidity in rural West-Java, Indonesia. Part I: Vital statistics based on cross-sectional surveys.

The first part of this article gives the summary result of 4 cross-sectional surveys conducted in 3 rural villages in West Java. It is expected that these surveys provide the researchers with more precise data on perinatal mortality and its associated causes in order to plan and implement the Tanjungsari Intervention Study (1986-1990). This comprises a mapping and numbering survey, and a census survey. Based on a sampling frame of 7964 houses, a systematic sample (one in eleven) was drawn for the Household and for the Married Women Surveys. The survey results yield some basic demographic indicators, occupational information and data on education. Also data on environmental health and vital statistics are presented. It is shown that the crude birth rate is 40 per thousand and that the estimated infant mortality rate reaches a figure of 120%. Furthermore, during individual interviews data was collected on characteristics, attitudes habits as well as on reproductive behaviour, of all married women under 50 years of age.

Adolescent

[Diagnosis and management of habitual reproductive wastage].

Our recent 10 years statistical survey at Keio University indicates that 1,877 spontaneous abortions are recorded in total 9,200 pregnancies, thus showing approximately 16.95 per cent wastages in known conceptions. In the present study, possible statistics on reproductive wastages are collected and summarized, then comprehensive examinations on the causes of habitual abortion were performed on our registered patients. Appropriate therapy was selected and its clinical result was also analysed. Eight hundred and thirty eight couples were registered as repeatedly or habitually aborted patients. Among these, 124 women repeatedly aborted due to congenital uterine anomaly, mainly bicornuate or arcuate uterus. A new method to evaluate uterine deformities related to abortion rate was introduced, while basic research was also performed to elucidate exact mechanism of abortion in these uteri by analysing distribution of arteries in both abnormal and normal control tissues. The results indicate that numbers of uterine arteries were significantly reduced in congenital abnormal uterus as compared to control. An ideal metroplasty was introduced from the research results. Twenty four children were born after 27 metroplasties, while no full term baby was delivered in 96 pregnancies before surgical operation. Fifty four women were suffering from habitual abortions due to chromosomal abnormalities among 639 couples examined. Karyotype analysis indicates that most frequent abnormalities were translocations, inversions as well as other variants. Extremely high incidence of spontaneous abortions were observed in each type of abnormality, suggesting ample time should be payed for genetic consultation. Luteal insufficiency and other diseases including anti-phospholipid syndrome were detected, however other 351 cases showed no significant abnormality except HLA compatible among the couples.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Habitual

[An attempt of introduction to prosthodontics of a non-contact device for measuring small configurations. Determining configurational changes during the individual steps of denture fabrication].

Denture fabrication involves a number of complex operations that have an effect on reproduction accuracy during each step of the process. Traditionally, metal patterns act as the standard for the mechanical properties of the main materials used in denture making. This means that doubts still remain in cases where the mucous membrane, with its complex configurations, is the object of investigation. The non-contact measuring instrument using laser light (known hereafter as "measuring instrument") enabled measuring small configurations. The measuring instrument enabled measurement of physical configurations that up to now were considered impossible to measure. The fabrication process up to creation of a denture base with the mucous membrane as the basic pattern was divided into four steps for measurement: mucous membrane, impression material, plaster and resin. The measuring device simultaneously carried out qualitative and quantitative analysis in three dimensions for all steps. Processing of test materials was unnecessary so that measurements could be accomplished in a very short time. Measurements revealed a variety of features, including those that are not affected by the physical properties of the materials for measurement. It was also possible to systematically investigate the various changes that take place during denture fabrication with the mucous membrane acting as the basic pattern. The following results were obtained: 1. The experiment confirmed possible application in dentistry of a non-contact device that uses laser light to measure extremely small configurations. 2. Results hint at the possibility of quantitative measurement of objects that cannot be directly measured with conventional methods. 3. During fabrication of dentures, it is very easy for changes in the total configuration to occur when taking impressions. Minute changes in the configuration occur on the surface when taking the plaster cast. During the final stage of the resin base, the tiny configurations became flat and resembled the configuration of the impression more than the original configuration of the mucous membrane.

Denture Bases

Electrophysiological aspects of human sphincter function.

In order to investigate the electrophysiology of the human internal anal sphincter and two current concepts of sphincter function, simultaneous manometric and electrical recordings were made from circular smooth muscle of the internal anal sphincter in the resting state and during reflexly induced sphincter relaxation. Three groups were studied: seven normal subjects, 25 patients with functional bowel disease, and seven patients with external sphincter paralysis due to spinal cord lesions. In the resting state slow waves of alternating potential (basic electrical rhythm or BER) were recorded in all subjects. Two types of waves were present, a constant sinusoidal pattern or a spindleshaped pattern. Either pattern was consistent for a given individual. Frequency of BER in the internal sphincter was higher than that recorded in any other gastrointestinal muscle. Our findings indicate that the BER recorded from the internal anal sphincter originates in this muscle. This activity may represent a specialized feature of sphincteric muscle since BER cannot be recorded from isolated nonsphincteric circular muscle. Reproduction of the two patterns of BER by an electronic model suggests that BER, as recorded by this technique, results from a summation of a number of electrically active cells in contact with the recording electrodes. Inhibition of BER occurred when sphincter relaxation was reflexly induced by rectal distension. Both inhibition of BER and degree of sphincter relaxation were proportional to the strength of rectal stimulation, suggesting that strength of stimulus determines the number of active cells which are inhibited. The associations of high frequency of BER with high resting pressure, and of inhibition of BER with sphincter relaxation suggests that maintenance of sphincter tone is an active process that is governed by BER.

Adolescent

Genetics of factors affecting the life history of Drosophila melanogaster. I. Female productivity.

Starting from four basic strains of Drosophila melanogaster, two laboratory strains (cn bw, Tokyo) and two isofemale lines (B-102, B-103) originated from a wild population in Texas, we constructed by repeated backcrosses through females for 20 or more generations a total of 16 strains of all possible combinations between the chromosome sets and cytoplasmic classes. Females from these 16 synthesized strains were then examined for their reproductive performance during their entire life span.---The chromosome set from the cn bw strain was found to associate with the highest female productivity when the age of females was very young, but these females ceased their reproduction and died relatively earlier, resulting in a smaller number of total progeny. The B-102 and B-103 chromosome sets, on the other hand, were associated with the lowest productivity when the females were young, but they lived and continued reproduction longer, resulting in a larger number of total progeny. The Tokyo chromosome set was associated with female productivity intermediate between the other two groups.---Cytoplasmic factors were found to affect the productivity of young females, with the cytoplasm from the cn bw strain associated with the highest productivity. Longevity was not cytoplasmically affected.---There was a clear interaction in female productivity between the Tokyo chromosome set and the cytoplasm from the Texas isofemale lines; the lifetime female productivity, as well as longevity, associated with the Tokyo chromosome set was found to increase considerably when it was substituted into the cytoplasm of the Texas isofemale lines. This chromosome-cytoplasm interaction appeared to be independent of the two systems of hybrid dysgenesis.

Chromosomes

The role of Cayo Santiago in primate field studies.

Cayo Santiago has provided the opportunity to study primate biology in a free-ranging neutral environment free of provocative human influences. Rarely, if ever, does such a situation occur in natural rhesus habitats in Asia. This Cayo Santiago advantage has permitted fine-scale analyses of the details of behavior, ecology, reproduction, genetics, demography, and pathobiology with a greater degree of precision than is possible in the field. At the same time, research on Cayo Santiago has provided valuable baselines for comparative work with natural populations in Asia. Field and laboratory work with the Cayo Santiago colony has produced an impressive number of pioneering studies, from the first investigations of Carpenter in the late 1930's, to the recent demonstrations of Kessler and Rawlins on the demographic role of tetanus in rhesus population ecology and the effectiveness of an inoculation program in eliminating infectious disease. Few, if any, primate colonies have had such a productive interface of naturalistic studies of behavior and ecology with basic biomedical research.

Academies and Institutes

Women's reproductive health--challenges for the 1990s.

Health policy makers, program planners and donor agencies have paid little attention to issues surrounding women's reproductive health. This paper will look at reproductive health issues surrounding pregnancy and childbirth, the accessibility and safety of contraception, and reproductive tract infections. The gross social injustice caused by high maternal mortality can no longer be ignored. Nor can we ignore the much larger numbers of women who suffer life-long health impairment resulting directly from the health hazards associated with pregnancy and childbirth. The challenge is to reduce maternal mortality by at least 50% by the year 2000. If these challenges are not faced, the 1990s may very well be remembered as the decade that saw the largest numbers of women dying in childbirth and pregnancy. The 1990s will see the addition of some 300 million couples to the reproductive age group. These couples will need access to good sexual health care, including safe and effective contraception, and prevention of reproductive tract infections and sexually transmitted disease. The biomedical consequences of reproductive tract infections are, among others, fetal wastage, low birth weight, carcinoma of the cervix, infertility and ectopic pregnancy. In addition to these consequences, there are the psychological, social and economic costs of these diseases. Some suggestions for meeting these challenges are put forward. These include building on existing programs and expanding available resources to help women to attain health, dignity, and their basic human rights.

Female

The dynamics of vector-transmitted diseases in human communities.

The development of vector-transmitted disease models and their application to field studies is reviewed. The key concepts of the basic rate of reproduction and disease transmission threshold are explained, and their application to disease control briefly illustrated. The complications involved in producing appropriate models are discussed for the case of the trypanosomatid parasites Leishmania and Trypanosoma that frequently have more than one vertebrate host and are often fatal in the human host. A two-species, vector-borne disease model allows a quantification of the role of animal reservoirs in maintaining human diseases. Human prevalence may be determined more by the parasitological characteristics of wild reservoir species, about which little is generally known, than by any other single feature of the complex interaction between parasites, vectors and hosts. Domestic animals are often ideal reservoirs, maintaining large numbers of vectors and considerably enlarging the parasite pool. When vector-transmitted diseases are fatal to the human host, human and vector dynamics interact in ways which may cause epidemic cycles, low-level endemic equilibria or disease extinction. For both leishmaniasis and trypanosomiasis it is suggested that a very small number of chronic human cases can maintain the disease in the human population over long periods of time between epidemic outbreaks. They may also be important in the maintenance of geographically distinct foci, characteristic of human trypanosomiasis in Africa. Finally there is a plea to establish a tradition of field observation leading to, and being directed by, mathematical models which in turn are modified as the observations accumulate. All too often, one-way traffic between the two results in slow, or misguided, progress.

Animals

Controlled ovarian hyperstimulation for the new reproductive technologies.

The aim of controlled ovarian hyperstimulation (COH) is to induce multiple morphologically and functionally adequate follicles with the aim of harvesting multiple fertilizable oocytes. We compared several treatment regimens with different FSH/LH ratios: group I was the basic 2 human menopausal gonadotropins (2hMG) protocol in which 2 ampules of hMG were administered starting on day 3 of the cycle; group II was the basic 2hMG in which 2 ampules of "pure" follicle stimulating hormone (p-FSH) were added on day 3 and 4; group III was the 2 FSH protocol in which 2 ampules of p-FSH were administered beginning on day 3; finally, group IV was the 4FSH: 4 ampules of p-FSH on day 3 and 4 followed by 2 ampules of p-FSH daily. The reference regimen was the 2hMG. Except for the higher rate of immature oocytes in 2FSH and 2hMG protocols, the number of preovulatory oocytes and fertilization rate were similar in all protocols. No differences occurred in the pregnancy outcome. The low dose Lupron (LDL) stimulation was an experimental protocol applied to two groups of women who had previously failed COH. Eight women who had a premature luteinization and 8 women who showed a low response agreed to participate in the protocol. Ten micrograms of the GnRH agonist leuprolide acetate (Lupron) were injected subcutaneously every 6 hours starting on cycle day 2 and menotropin stimulation was begun on day 3-5, according to individual patient response. The LDL protocol was successful in determining a favourable estradiol pattern and fertilizable oocytes.

Drug Administration Schedule

Active cross-bridge model. Reproduction of the myocardial force-length-time relation and the left ventricular pressure-length-time relation in systole.

A mathematical model has been derived to describe cardiac contraction. This model assumes (1) a linear end-systolic force-length relation for the intact left ventricular (LV) myocardium with proportionality constant Ec, and (2) that the rate of increase in the number of active cross-bridges is proportional to the number of cross-bridges capable of being activated at that moment with a proportionality constant Ka. Quantitative evaluation of this model was performed using parameter values measured in the normal human LV. The model predictions agreed well with many earlier experimental data concerning the myocardial force-time relation, myocardial force-velocity-length relation, systolic time interval-afterload relation, time-varying elastance concept, several LV end-systolic relations, and LV dP/dtmax-end-diastolic volume relation. Moreover, two important basic properties of contractile proteins, i.e., the maximal force-generating capacity and the rate of activation of cross-bridges, were evaluated in the model from the values of Ec and Ka, respectively. Although no definitive biological proof has yet been provided for the assumptions, this model might mathematically integrate the myocardial and ventricular dynamics over the entire systole and then provides a new method for evaluation of the human LV systolic function from two basic properties of active cross-bridges.

Blood Flow Velocity

Synchronization of estrus in dairy heifers: a field demonstration.

Use of prostaglandin F2 alpha to synchronize estrus was demonstrated over 3 yr with 2966 dairy heifers in 45 herds. Reproductive status of all heifers was determined before any injections occurred. Anovulatory heifers (8.3%) were not injected or inseminated. Ovulatory heifers received one intramuscular injection and most heifers received two injections of prostaglandin F2 alpha spaced 11 d apart. Observations for estrus and insemination were scheduled and performed by dairy farmers. Insemination of heifers occurred 12 h after detection of estrus or at 80 h after second injection of prostaglandin F2 alpha. Pregnancy rate averaged 50.9% but varied from 0 to 100%. Pregnancy rate after insemination according to estrus (62.8%) was greater than when insemination was at 80 h (39.1%). Low pregnancy rates were associated with limitations in basic management of heifers before or during insemination. Managerial limitations were in timing insemination, range of ages or weights of heifers housed together, number and types of vaccinations, season and diet, frequency of observing heifers for estrus, and number of straws of semen thawed concurrently. Managerial factors that affect fertility are similar whether or not estrus is synchronized. Although agents used to synchronize estrus do not affect fertility directly, managerial limitations on fertility may be accentuated by increased intensity of activity associated with synchronization.

Animals

Effect of laval breeding conditions on the morphological, ovarian and behavioral characteristics of Anopheles pharoensis of the emerged females.

Under laboratory conditions, morphological, ovarian and behavioral characteristics of Anopheles pharoensis females were found to be affected by a combination of 3 larval environmental factors: quantity of food, density of larvae and salinity of the rearing medium. Size and weight of the emerged females were decreased by lowering the quantity of food (basic ration), increasing the population density of larvae (200 larvae/pan) and increasing the salinity of the rearing medium (1/5 dilution of Sea water). Embryogenesis and behavior of the female were also affected by the larval environmental factors; the female emerged with the undeveloped stag of the ovaries (Christophers's stage I), needs a multiple feeding with 2 blood meals required, at times, to reach the gravid stage and produce the first batch of eggs. The female emerged with fewer number of ovarian follicles and thus affecting the number of produced eggs. The emerged female takes as maximum 4 blood meals to lay 3 batches of eggs during the life cycle (8 days).

Animals

Monoclonal antibodies directed against basic fibroblast growth factor which inhibit its biological activity in vitro and in vivo.

A panel of four murine monoclonal IgG1 antibodies (mAbs) to a recombinant form of basic fibroblast growth factor (bFGF) was produced using somatic cell fusion techniques. Non-linear regression analysis of radioimmunoassay data for each mAb yielded the following dissociation constants (nM) for their interactions with bFGF: DE6 (0.822); AF11 (2.0); FE8 (2.31); and DG2 (20.0). One of the mAbs, DG2, was identified as a bFGF neutralizing antibody on the basis of its ability to inhibit, in vitro, the binding of [125I]-bFGF to high and low affinity bFGF sites on cultured baby hamster kidney cells and bFGF-induced [3H]-thymidine incorporation in cultured 3T3 cells, and in vivo, the angiogenic response to bFGF in a rat kidney capsule model of angiogenesis. The other mAbs displayed varying inhibitory activities in these assays. These mAbs, particularly DG2, may be well suited for a number of applications in bFGF research including immunoassays, immunohistochemical studies, and as functional antagonists of bFGF for examining its role in physiological processes such as reproduction, growth, and development.

Animals

Histological aspects of cervical ripening.

There is a close relationship between the rate of the uterine cervix opening during parturition and the presence or absence of a completely ripened cervix. In order to learn the basic pattern of the ripening of cervix, histological and histochemical studies were performed on the human uterine cervix during pregnancy. It was noted that the collagen bundles disintegrated into fine fibers and also underwent quantitative changes during the ripening process of the cervix. During pregnancy, the number of connective tissue cells was increased, but that of mast cells was decreased. Acid mucopolysaccharides in the cervical ground substance were found to increase in late pregnancy.

Adolescent

The ovarian prorenin-angiotensin system. Lessons from IVF.

Recent evidence suggests that prorenin and other active components of the renin-angiotensin system may be linked to ovarian physiology. Prorenin, the inactive form of the enzymatically active renin, is present in the fluid of mature human ovarian follicles in concentrations more than 10 times higher than that found in the plasma of women undergoing ovarian stimulation. Only 1% of the renin in follicular fluid is in active form. Concentrations of prorenin in fluid of immature follicles are lower than levels detected in concomitantly aspirated mature follicles. Study of prorenin levels disclosed a positive correlation to testosterone and E2 in fluids of mature follicles. Plasma prorenin increases about twofold at midcycle at the time of the LH surge; the peak of prorenin is sustained for about 40 hours. In patients undergoing ovarian stimulation for IVF, hCG administration results in much higher plasma prorenin levels and the height of prorenin response is directly related to the number of mature follicles. It peaked 4 to 6 days after hCG injection and then fell, close to baseline, by about 12 days after hCG administration. Examination of the time course of hormonal changes in response to hCG revealed a temporal relationship between prorenin and both plasma E2 and progesterone. In women who conceived, prorenin began to rise again on days 8 to 12 after embryo transfer when endogenous hCG was detected in the blood. No such changes in prorenin occurred in women with ovarian failure who conceived after transfer of a donor egg. These findings indicate that prorenin is produced by the mature follicle and the corpus luteum in response to LH/hCG. Since angiotensin II affects intracellular calcium and phospholipase activity, there are many potential roles for prorenin via angiotensin II action. Putative actions of the ovarian renin system may include control of oocyte maturation, ovulation, ovarian blood flow, and ovarian steroid biosynthesis. Future work to elucidate the function of this new renin system may have relevance to many basic and clinical aspects of human reproduction.

Enzyme Precursors