Enhancement by glucocorticoid deficiency of the increase in cycloleucine accumulation induced in rat thymocytes by triiodothyronine.

In previous studies, we have demonstrated that 3,5,3'-triiodothyronine (T3), either added to suspended media in vitro or injected acutely in vivo, increases the in vitro accumulation of the non-metabolized amino acid cycloleucine (CLE) by thymocytes harvested from weanling rats. We now report that this reponse is greatly enhanced by prior adrenalectomy of the donor rat. In vitro, a significant increase in CLE accumulation in thymocytes from adrenalectomized rats was induced by T3 at a concentration of 1 x 10-10 M, while a concentration of 1 x 10-6 M was required to produce a similar and significant effect in thymocytes from intact animals. In adrenalectomized animals, a single iv dose of T3 (0.5 microgram/100 G bw) significantly increased the in vitro accumulation of CLE in thymocytes harvested two hours later. In contrast, ten-times that dose was ineffective in control animals. Increased sensitivity to T3 was abolished by physiological replacement doses of hydrocortisone. The data are consistent with the well-known opposing effects of physiological levels of thyroid and glucocorticoid hormones on the growth and function of lymphoid tissue in vivo and, together with other findings, suggest that thyroid hormones modulate the cellular accumulation of amino acids in the intact animal.


Comparative characterization of the basic forebrain cortical zones in Emys orbicularis (Linnaeus) and Testudo horsfieldi (Gray).

The neuronal and synaptic organization of forebrain basic cortical zones in Testudo horsfieldi and Emys orbicularis and their dendritic spines have been studied using Nissle, Golgi and electron microscopic methods. It has been shown by comparison of the results that the two spicies have marked differences in the structural organization of the forebrain cortical zones. The cortical formation in Testudo horsfieldi is different from that of Emys orbicularis in a greater diversity of neuronal types, smaller size of neurons, smaller cell density in each cortical zones, the presence of horizontal dendritic terminals in dorsomedial dorsal cortex, the absence of the large neurons in dorsomedial medial cortex, ect. Moreover, in both species the dorsomedial dorsal cortex in comparison with medial and lateral cortex is characterized by a marked complexity of the structural organization (diverse neuronal composition, the presence of the stellate cells, the highest cell density, the smallest neuronal size). The investigation of spines in the different dendritic levels (proximal, middle and distal) of neurons in three cortical basic zones has been shown that in both species it has been observed the tendency to increasing of the spine density from proximal to distal part of dendrite. at all dendritic levels noninvaginated forms of spines predominated. Invaginated spines were recorded at the proximal and middle levels of dendrites and contain more organelles and inclusions than noninvaginated spines. In Testudo horsfieldi and Emys orbicularis differences of spine thin structure and spine density in the cortical basic zones were revealed. Moreover, in both species the spines of dorsomedial dorsal cortex were more numerous, more variable in shape, more abundant in organelles. It was there that a bush-like distribution of spines was found which in evidently a special form of synaptic organization of cortical neurons. The above features of this cortical zone indicates a higher degree of differentiation, suggesting that the dorsomedial dorsal cortex is phylogenetic youth as compared with hippocampus and lobus pyriformis.


[The structure of the neostriatum in the rat].

The neostriatum of the adult rat was investigated by means of the Golgi-rapid-impregnation technique. The fasciculi of the capsula interna which are embraced by the dendrites of the spiny neurons in a rank-like manner represent the structural framework of this brain region. The cellular population of the neostriatum is composed of at least five morphologically different neuron types: 1) Spiny neurons which by far outnumber the other types; 2) Few spiny neurons; 3) Large spiny neurons (giant neurons); 4) Small sized aspiny neurons; 5) Spider shaped aspiny neurons. The spiny neurons (type 1 neurons) and the small sized aspiny neurons (type 4 neurons) are considered to be striatal interneurons; the large sized aspiny neurons (type 3 neurons, giant neurons) and the spider-shaped aspiny neurons (type 5 neurons) are suggested to be striatal efferent neurons. The functional correlation of the few spiny neurons (type 2 neurons) is not possible as yet. A dense fiber plexus extends throughout the neostriatum unubiquitously. The axon type which appears to be distinctive according to morphological criteria - fine varicose axons, so called beaded axons - is supposed to be the terminals of the mesencephalic dopaminergic neurons. The heavily impregnated aggregations which are characteristic of the striatum after using the Golgi-rapid-treatment are thought to represent conglomerations consisting of neurons, glial cells and beaded afferent fibers.


The origin of reticulospinal fibers in the rat: a HRP study.

The distribution as well as morphological characteristics of brain stem reticular neurons projecting to spinal cord both of aminergic and non-aminergic natures in the rat was investigated by means of the retrograde horseradish peroxidase (HRP) method. For the identification of aminergic neurons, a combination of HRP technique and monoamine-oxidase staining as well as a pretreatment of 6-hydroxydopamine and 5,6-dihydroxytryptamine (5,6-DHT) was applied. Following the injection of HRP to the cervical, thoracic and lumbar cord, a remarkable number of neurons in the nuclei reticularis ventralis (rv), reticularis lateralis (RI; Meesen & Olszewski), reticularis gigantocellularis, reticularis pontis caudalis, reticularis pontis oralis (rpo), and a small number of cells in the nucleus reticularis dorsalis dorsalis as well as the mesencephalic reticular nuclei were found to be labeled. In the case of cervical injection, HRP labeled cells were also found in the nucleus reticularis parvocellularis, adjacent to the nucleus tractus spinalis n. trigemini oralis, in which labeled neurons were observed. Within Rl, ventral division of rv and lateral part of rpo, the labeled noradrenaline neurons in A 1, 3 and 7, respectively, were found intermingled with the non-aminergic labeled neurons. Many neurons in the nucleus raphe magnus (ram), obscurus (rao) and pallidus (rap) were labeled. From the fact that there was a marked decrease in the number of the labeled cells in rao, rap, and a slight decrease in ram after 5,6-DHT treatment, it was suggested that the majority of labeled cells in rao, rap and a partial number of labeled cells in ram are serotonergic.


Interaction between theophylline and oestrogen in the rat uterus.

Theophylline alone or in the presence of 0.001, 0.01, 0.1 or 1 microgram oestradiol-17 beta/100 g body wt increase uterine RNA and protein content 6 h after administration. Uterine oedema induced by physiological doses of oestradiol-17 beta was increased further in the presence of theophylline. Theophylline decreased the number of eosinophils in the blood and concurrently decreased oestrogen-induced uterine oesinophilia at doses of 0.01, 0.1, 1, 10 or 30 micrograms oestradiol-17 beta/100 g body wt. Oestrogen binding by uterine eosinophils in vitro increased in the presence of theophylline. This effect of theophylline could explain the increase of oestrogen-induced uterine oedema in vivo.


Biological and binding activities of equine pituitary gonadotrophins and pregnant mare serum gonadotrophin.

The biological and binding activities of pregnant mare serum gonadotrophin (PMSG) were compared with those of highly purified FSH and LH from the pituitary gland of the same species. Pregnant mare serum gonadotrophin showed activity in bioassays considered to be specific for both FSH (e.g. the Steelman-Pohley ovarian augmentation test and cyclic AMP production by rat seminiferous tubules) and LH(androgen production by rat Leydig cells), as well as activity in a variety of radioreceptor assay systems previously considered to be specific for one of the two types of gonadotrophin. The potency of PMSG was high compared with that of purified ovine FSH or LH standards in all assays but PMSG was considerably less active than equine FSH and LH in vitro. In radioreceptor assays employing rat, pig and horse tissues, the activity of PMSG was equivalent to only 1--5% of equine FSH in competing for FSH-binding sites and only 3--35% of equine LH in competing for LH-binding sites. Pregnant mare serum gonadotrophin was least active in homologous binding assays with horse testis and equine LH as radioligand. In the rat Leydig cell bioassay, the activity of PMSG was only 2.0% that of equine LH. Furthermore, in some assays equine LH was found to resemble PMSG in exhibiting a high degree of FSH-like activity that could not be accounted for by cross-contamination. The FSH immunoactivity of equine LH was less than 0.5% that of equine FSH, but equine LH was up to 63% as potent as equine FSH in competition for FSH-binding sites and it was 20% as active in the Steelman-Pohley ovarian augmentation bioassay. Equine LH did not, however, show the expected activity in the cyclic AMP production bioassay. Thus, the FSH-binding sites and physiological receptors may not be identical. Overall, comparison of PMSG with pituitary gonadotrophins from homologous species shows that the apparent dual activity of PMSG may not be a unique feature of this pregnancy hormone since equine LH also exhibits some FSH activities. The chemical resemblance between PMSG and equine LH is noteworthy in this regard.


Concentrations of luteinizing hormone in the plasma or hemicastrated cockerels.

The concentrations of LH in plasma were measured, using a radioimmunoassay, during sexual development of intact cockerels and cockerels hemicastrated at 2 weeks of age. The pattern of LH secretion during maturation was characterized by a series of at least four consistently observed periods of rising and falling blood levels of the hormone. Levels of luteinizing hormone were higher in hemicastrated than in intact cockerels between 2 and 4 weeks after the operation (4--6 weeks of age) and then fell to values below those seen in intact cockerels between 8 and 11 weeks of age. Thereafter, until 28 weeks of age, levels of LH in plasma in both hemicastrated and intact birds were similar. The transient changes in LH concentration after hemicastration were thought to be a direct consequence of an alteration in the concentration of testicular steroids in the blood after the removal of one gonad.


Determination of tamoxifen and an hydroxylated metabolite in plasma from patients with advanced breast cancer using gas chromatography-mass spectrometry.

An assay has been established for the selective measurement of tamoxifen and its monohydroxy derivative, metabolite B, in human plasma. The assay was used to examine the concentrations of these compounds, relative to oestradiol-17 beta, in the plasma of patients undergoing tamoxifen therapy for advanced breast cancer. Oral administration of the drug (20 mg twice a day) raised the level of tamoxifen in plasma to approximately 200 ng/ml 20 days after the commencement of treatment. This level was 3000-fold higher than the corresponding concentration of oestradiol which remained within the range for post-menopausal women. Metabolite B was present in plasma at a much lower concentration than tamoxifen although in considerable excess over oestradiol. The overall results are discussed in relation to the possible mechanism of action of the drug.


Genetic analysis of multiple sclerosis in Orkney.

In a family study of all patients with multiple sclerosis (MS) in Orkney, the number of inbred among patients, although high for Britain, is not higher than the number among controls, and the inbreeding coefficients appear to eliminate recessive involvement of rare genes from the aetiology. The kinship coefficients show that the ancestries of patients and controls are closely enmeshed, and eliminate from the aetiology involvement of recently introduced genes dominant or codominant in effect. Family histories show that single locus inheritance is unlikely unless penetrance is very low. Multifactorial genetic involvement is much more likely, and it is compatible with all recent findings; on this hypothesis heritability estimates, not altogether satisfactory because of the limited number of patients in the population, suggest that the genetic contribution to the aetiology of the disease in Orkney is only moderate.


Ischaemic heart disease mortality risks for smokers and non-smokers.

Although many studies have shown that smoking is associated with an increased risk of death from ischaemic heart disease (IHD), and that the increase appears to vary with age and amount smoked, there has been little formal specification or estimation of the relationship. In this paper two alternative models are tested, using data for different ages and levels of smoking from four major studies in three countries. One model explains 80% of the variation in mortality in terms of a positive linear function of the number of cigerettes smoked, the parameters of which decrease with age. We estimate that every cigerette smoked per day increases the risk of dying from IHD by as much as 35% at ages 35 to 44, reducing to 2% at ages 65 to 74. The risk attributable to smoking may account for more than 80% of IHD deaths of men aged 35 to 44, and 27% of those of men aged 45 to 64. Although the relative risk is highest for younger age groups, the absolute risk of death from IHD that is attributable to smoking increases with age. The evidence suggests that both are increasing with time.


The influence of obstetric procedures and social and cultural factors on breast-feeding rates at discharge from hospital.

The influence of obstetric factors on breast-feeding rates at discharge from St. Thomas's Hospital in 1969 and 1970 has been examined in 1356 primiparous mothers delivering healthy babies. Induction of labour and assisted delivery were significantly associated with lower breast-feeding rates. The association could not be explained by differences in social class, country of origin, birthweight, anaesthesia in labour, or medical reasons for induction and assisted delivery. The most likely explanation is that induction and assisted delivery are associated with delay in starting breast-feeding. However, trends in obstetric management of labour and delivery are unlikely to have a large influence on the incidence of breast-feeding compared with the influence of social and cultural factors.


Selective screening: theory and practice based on high-risk groups of cervical cancer.

Using data taken from the organised mass screening system in Finland, risk indicators of cervical cancer were identified in order to define a high-risk group which could then be used for selective screening of cervical cancer. Single risk factors classified at best 39% of the cases into a high-risk group of 8%. A combination of risk factors by different statistical methods was applied, but the results were essentially the same. In order to find a high-risk group small enough to yield a reduction in costs, the number of cases originating from the low-risk group was increased. Theoretical calculations showed that for selective screening to be effective, the risk of disease in the high-risk group relative to that in the low-risk group must be greater than that implied by current knowledge of cervical cancer epidemiology. It was concluded that selective screening has only a limited applicability.


Nurses in the community: a manpower study.

High priority is at present being given to the expansion of health visiting and home nursing services as part of the change of emphasis from institutional to community care. The aim of this study was to provide nurse managers in two regional health authorities with basic information about community nurses with could be used for service planning and development. The results of the study emphasise the particular problems of staffing the community nursing service in inner London, where home nurse and health visitors are younger, more recently appointed, and relatively less experienced than staff in other parts of the regions. High turnover rates and chronic recruitment difficulties in inner London prevent nurse managers from maintaining both the level and the quality of the services they aim to provide. Until these problems are remedied there is little prospect of achieving any significant shift in the balance of care in inner London.


Factors in child burn and scald accidents in Bradford 1969-73.

A study has been undertaken of burn and scald accidents to children in Bradford. In the first part, 1577 accidents treated in the Bradford Royal Infirmary between 1969 and 1973 were analysed by city ward of residence of the patient and these were correlated with 14 social and demographic characteristics of the wards. A correlation was found between burn and scald accidents and New Commonwealth immigrants and overcrowing. In the second part, 78 families at the burns clinic were interviewed. Similar patterns to those in the larger study were found. Although clinical impressions emerged concerning the details of the accidents the interviews did not provide any explanation for the main findings.


The influence of some correlates of blood pressure on its distribution in an Indian rural community.

A door-to-door investigation of casual blood pressure (BP) was carried out in 1325 adults in an Indian rural community to study its distribution and the influence on BP levels of some correlative factors--namely, age, sex, weight, build, and socioeconomic status. Systolic and diastolic levels of BP rose with increasing age, weight, and build. However, the socioeconomic status of respondents did not significantly influence their BP levels. After the age of 40, women had considerably higher levels of systolic blood pressure (SBP) than men. Evidence was found of multimodality, espically in diastolic blood pressure (DBP) distributions. The need is emphasised for an extensive investigation to obtain more accurate and generalised results, utilising the technique of blood pressure measurement recommended by the World Health Organisation (WHO, 1959).


Follow-up studies on the distribution of haemoglobin levels in female farm workers.

Haemoglobin concentrations in about 1000 women agricultural workers in Japan were measured every year, except in 1972, during the period 1967-77. Improvements were noted in the course of this investigation, and these were predominantly associated with the fact that those in the study community began to pay attention to the problem of low haemoglobin levels and to improve their diet, with an increase in daily food intake, particularly of animal protein and iron. In addition, a marked decrease in anaemia caused by hookworm also played an important role. In this paper, the change in haemoglobin concentration during the period of study are described and the aetiology is discussed.


Community diagnosis of physical growth of infants based on monitoring in a routine preventive service.

The physical growth pattern of infants aged from one month to two years was studied in a lower middle class community in Jerusalem. Weight and length were measured at one month and at three, six, 12, and 24 months. In each age and sex group there were at least 200 children. At one month and 24 months the percentage of children below the 10th percentile for weight and also for length was higher than expected, although severely impaired linear growth was observed in only 0.5% of males and 1.3% of females at 24 months. The percentage of overweight infants was highest at three months (6.2% of males and 5.2% females). In the light of these findings, we discuss the feasibility of accurate monitoring of physical growth in maternal and child health clinics; the possibility of an association between maternal stature and the high percentage of children below the 10th percentile for length; and the association between food intake and growth pattern.


A mathematical model of a heroin epidemic: implications for control policies.

An exponential model based on the infectious disease model of Kermack and McKendrick has been simplified to illustrate how the use of heroin spreads in epidemic fashion. A numerical simulation is arranged to show how the dynamics of spread are influenced by the original number of users, rates of conversion, and time of removal from the drug scene of those secondarily affected. The spread is significantly increased by small increases of those originally affected, in which case reduction of spread requires a large increase in rate of removal. The model indicates a strategy for intervention which is discussed in relation to policies for control of drug abuse.


Incidence of multiple births in an Indian rural community.

In this paper we report on the incidence of multiple births in a rural community of India in the period 1966-75. The incidence is an improvement on estimates reported earlier by various authors and the information would be useful for studying secular trends.


The relationship between retinal and tectal growth in larval Xenopus: implications for the development of the retino-tectal projection.

The modes of retinal and tectal histogenesis, as well as the patterns of terminal distribution of optic axons in larval Xenopus were studied, using anatomical techniques. We show that the retina grows by adding strips of cells at its ciliary margin. The pattern of retinal growth is asymmetrical along the dorso-ventral axis of the retina. On the other hand, the tectum grows by adding newly formed cells caudo-medially. The most rapid tectal growth takes place between stages 50 and 53, and thereafter only a small proportion of cells are added near the midline of the caudal tectum. Despite such incongruent modes of retinal and tectal growth, retinotopic order is maintained throughout larval life. We present here further evidence supporting the idea that connexions between the arrays of retinal and tectal cells shift progressively caudo-medially on the tectum during the period of growth. When the temporal pole of the retina is destroyed at various developmental stages, the density of degenerating synapses is always highest in the rostral pole of the tectum. Moreover, optic terminals stemming from the central retina spread caudally, invading newly maturing regions of the tectum. Quantitative analysis of the terminal distributions of optic axons suggest that orderly shifts in synaptic contacts between optic axons and tectal dendrites take place in the course of development. Ultrastructural observations on the maturing tectal neuropil are consistent with this view.


The utilization of an inhibitor of spermidine and spermine synthesis as a tool for the study of the determination of cavitation in the preimplantation mouse embryo.

The inhibition of spermidine and spermine synthesis by methylglyoxal-Bis(guanylhydrazone) (MeGAG) at concentrations of 5, 10 and 20 microM, induces a reversible metabolic quiescence of mouse embryos, cultured in vitro from the 2-cell stage, at an average of 10.2, 8.5 and 6.9 cell stages respectively. In contrast, the inhibition of putrescine synthesis by alpha-methylornithine (alpha-MeOrn) at concentrations up to 10 mM fails to inhibit blastocyst formation, as shown previously. Complete reversibility of this induced arrest of development is observed for treatments up to 31 h with MeGAG at 10 microM. In agreement with the biological clock theory of Smith & MacLaren's hypothesis, the delay in cavitation is proportional to the length of treatment. However, the average cell numbers of the 'delayed nascent blastocysts' of all treated embryos (21.8--24.2) are consistently lower than that of control embryos (33.6) irrespective of the duration of treatment. It seems therefore that under some experimental conditions, DNA and chromosome replication on the one hand and cytoplasmic maturation on the other may be desynchronized. This suggests a role for a cytoplasmic factor in the induction of cavitation.


Evidence for differential cellular adhesion as the mechanism of sorting-out of various cellular slime mold species.

Various authors have shown previously that if the amoebae of two species of slime molds are mixed they have the ability to sort themselves out. In the work reported here, the sorting-out of cells of several slime mold species was examined in clumps of cells in suspension. Cells of four species, Dictyostelium discoideum (Dd), D. mucoroides (Dm), D. purpureum (Dp), and Polysphondylium violaceum (Pv), were mixed in pairs in suspension and clumps of cells formed. Dd and Pv cells sorted out completely and formed separate clumps, each of single species. Both Dd and Dm, when mixed separately with Dp, formed clumps containing both species. Sorting-out took place in these clumps such that the cells of Dd and Dm partially enveloped the Dp cells. Finally, in the Dd-Dm mixtures, the Dm cells always sorted out such that they surrounded the Dd cells. When mixed in a 1:2 ratio (Dd:Dm) the Dm cells formed a complete shell around a sphere of Dd cells. Sorting-out of cells in clumps in suspension can occur by either of two possible mechanisms: response of cells to a chemotactic gradient or differences in cell surface strengths of adhesion (Steinberg, 1964). Mixing of two species in a clump of cells and observing the process of sorting-out permits one to distinguish between these two mechanisms (Steinberg, 1964). By such an analysis it was found that the sorting-out observed in mixtures of Dd and Dm is consistent with the mechanism of differential cellular adhesion. The major reasons for this are (1) when the adhesive properties of the cells are known to change the Dd cells began to move inside the clumps, (2) the Dd cells coalesced into islands rather than streaming inward independently, and (3) the Dd cells and cell masses did not lie at the center of the clumps but rather lay randomly within the clumps. The partial envelopment observed in the Dd-Dp and Dm-Dp mixtures and the separate clumps formed by the Dd-Pv mixtures are also consistent with differential cellular adhesion. They represent cases in which the interspecific strengths of adhesion are low (Dd-Dp and Dm-Dp) and near zero (Dv-Pv).


Changes in collagen ultrastructure, macroscopic properties and chemical composition of chick embryo cartilage induced by administration of beta-D-xyloside.

Nine-day chick embryos were injected with a beta-xyloside and their sternal cartilage was examined 3 days and a week later. Sterna from 16-day embryos showed a reduction in size as compared to controls, with little or no change in the fraction of extracellular space, and a significant decrease in tensile strength. At the ultrastructural level, collagen fibrils in control sterna were dispersed evenly in the interstitial space, with few contacts between adjacent fibrils. In sterna from treated embryos, almost all collagen fibrils were aggregated into clumps and arrays throughout the interstitial space, with fibril-free areas in between. No abnormalities could be detected in the morphology of individual fibrils or in the ultrastructure of the chondrocytes. The changes in spatial distribution of collagen were fully evident 3 days after drug administration. The hydroxyproline/DNA ratio was the same in control and treated sterna, and no change was observed in the type of collagen. The uronic acid/DNA ratio was reduced by 14% 3 days after drug administration and by 40% after a week. The degree of sulfation of chondroitin sulfate was reduced from 80% in control sterna to 40% in treated sterna; almost all of this chondroitin sulfate was attached to peptide and the sedimentation pattern of the proteoglycan resembled that of normal cartilage proteoglycan. The function of chondroitin sulfate in embryonic cartilage is discussed in terms of our results and others. It is suggested that a major physiological role of the proteoglycan is to control the spatial distribution of collagen fibrils as they assemble to form a cross-linked gel.


The time of action of three mutations affecting Drosophila eye morphogenesis.

Histology and clonal analysis are used to look at the time of action of the mutant Drosophila genes eyeless, eyeless dominant and sine oculis. The findings suggest that eyeless dominant has its effect during the first two larval instars, whilst eyeless and sine oculis act during the third larval instar.


The use of avian double monsters in studies on induction of the nervous system.

Ninety-eight duck double monsters (siamese twins) were studied between 48 and 72 h of incubation in whole-mount or serial-sectioned preparations. Each case was classified into one of four categories depending on the orientations of the two embryonic axes. In all classes, defects in primary neural induction of various parts of the embryonic nervous system were observed which depended to a large extent on the distance separating the anterior tips of the two notochords or on the relative positions of the notochords. Our observations suggest that: when the same inducing field of one embryo overlaps to a critical extent with that of the twin, the two inducers act as one; induction of forebrain and optic vesicles is purely prechordal; the notochord exerts an inhibition on induction of forebrain by prechordal mesoderm; and the presence of rhombencephalic structures depends on both prechordal and chordamesodermal interactions.


Cell number in relation to primary pattern formation in the embryo of Xenopus laevis. II. Sequential cell recruitment, and control of the cell cycle, during mesoderm formation.

Morphological evidence is presented that definitive mesoderm formation in Xenopus is best understood as extending to the end of the neurula phase of development. A process of recruitment of cells from the deep neurectoderm layers into mesodermal position and behaviour, strictly comparable with that already agreed to occur around the internal blastoporal 'lip' during gastrula stage 20 (earliest tail bud). Spatial patterns of incidence of mitosis are described for the fifteen hours of development between the late gastrula and stage 20--22. These are related to the onset of new cell behaviours and overt cyto-differentiations characterizing the dorsal axial pattern, which occur in cranio-caudal and then medio-lateral spatial sequence as development proceeds. A relatively abrupt cessation of mitosis, among hitherto asynchronously cycling cells, precedes the other changes at each level in the presumptive axial pattern. The widespread incidence of cells still in DNA synthesis, anterior to the last mitoses in the posterior-to-anterior developmental sequence of axial tissue, strongly suggests that cells of notochord and somites in their prolonged, non-cycling phase are G2-arrested, and thus tetraploid. This is discussed in relation to what is known of cell-cycle control in other situations. Best estimates for cell-cycle time in the still-dividing, posterior mesoderm of the neurula lie between 10 and 15 h. The supposition of continuing recruitment from neurectoderm can resolve an apparent discrepancy whereby total mesodermal cell number nevertheless contrives to double over a period of approximately 12 h during neurulation when most of the cells are leaving the cycle. Because of pre-existing evidence that cells maintain their relative positions (despite distortion) during the movements that form the mesodermal mantle, the patterns presented in this paper can be understood in two ways: as a temporal sequence of developmental events undergone by individual, posteriorly recruited cells as they achieve their final positions in the body pattern, or alternatively as a succession of wavefronts with respect to changes of cell state, passing obliquely across the presumptive body pattern in antero-posterior direction. These concepts are discussed briefly in relation to recent ideas about pattern formation in growing systems.


Correction of the maternal effect linked to the ac mutation, by injury of the egg, in the salamander Pleurodeles waltlii.

At the gastrula stage, deep irregular furrows appear on the animal hemisphere in embryos arising from ac/ac females and characterize a maternal effect (Beetschen, 1970). Disturbed morphogenetic movements (epiboly and invagination) frequently elicit exogastrulation or anomalies of later embryonic development. Pricking the animal hemisphere of the uncleaved egg with a micropipette prevents the occurrence of anomalies during gastrulation and neurulation in many embryos. Injection of normal oocyte nuclear sap or of normal egg cytoplasm into mutant female eggs does not improve that result. The partial correction of the maternal effect therefore appears to be consecutive to the injury of the cortical cytoplasm and/or the plasma membrane. Assuming that activation could be deficient, an electric shock was applied to freshly laid fertilized mutant eggs. It did not correct ectodermal anomalies but nevertheless seemed to increase the corrective effect of pricking when both treatments were applied.


Effects of x-rays on nerve-dependent (limb) and nerve-independent (jaw) regeneration in the adult newt, Notophthalmus viridescens.

The newt limb requires nerves for successful regeneration, but the jaw appears to be nerve independent. Among the current hypotheses for the regeneration-inhibitory action of X-rays is one proposing inactivation of nerves as the main cause. We decided to test this hypothesis by comparing the irradiation levels necessary for inhibition of limb and jaw regeneration. Jaws and left front limbs were exposed locally to doses of ionizing X-irradiation ranging from 250 to 2000 R at least 6 weeks prior to amputation of the jaw and both front limbs. After 90 days post-amputation all surviving animals were examined grossly for signs of regeneration. In addition, some of the controls and most of those receiving 250, 500 and 1000 R were processed for histological examination. All unirradiated limbs and jaws supported regeneration. Those exposed to 250 R also regenerated, but a third of the jaws were hypomorphic. At 500 R and above, neither jaws nor limbs regenerated. Since both systems were affected by similar doses of X-rays, it appears that nerves are not the primary X-ray target in adult newts.


Crinkly-tail, a mild skeletal mutant in the mouse.

Crinkly-tail, cy, is a new recessive mutant with imperfect penetrance, in chromosome 4 of the mouse. The only abnormality is in the shape of the vertebrae for one, more rarely two, lengths of the region C9 to C14. This is expressed briefly in the 11-day-old embryo as a duplicated tail gut. None of the mechanisms operating in most of the 20 known tail mutants in the mouse operates in crinkly-tail. The defect is probably due to misallocation of the tissue derived from the primitive streak.


Molecular differentiation of inside cells and inner cell masses isolated from the preimplantation mouse embryo.

Clusters of inside cells (ICs) were isolated immunosurgically from morulae and early cavitating blastocysts, and cultured for varying periods in vitro. The ICs responded to their changed position by transformation to a blastocyst-like vesicle and also showed a correlated synthesis of trophectodermal-marker polypeptides. Both changes were inhibited by alpha-amanitin, indicating that transcriptional events are involved in this response to changed position. Inner cell masses (ICMs), isolated immunosurgically from expanded blastocysts, did not undergo a morphological transformation to a blastocyst-like structure and did not show a corresponding and complete change in synthesis of trophectodermal-marker polypeptides. Elements of the change in polypeptide activity were, however, present, suggesting an ineffective response to position by the ICMs.


The orientation of the visuotectal map in Xenopus: developmental aspects.

Rotations and translocations of the eye anlage were performed in Xenopus embryos of stages ranging from 21/22 to 30. Some of the operations involved grafting wild-type eye anlagen into albino host orbits. Operations were performed under a variety of operating media and conditions. In later larval life, or after metamorphosis, the visuotectal maps from the operated eyes were recorded electrophysiologically. Results fell into two classes. In the majority, the orientation of the visuotopic map corresponded to the orientation of the eye at the time of recording. In the minority the visuotopic maps were 'compound', consisting of two parts each with its own independent orientation. The organization of the compound maps was such that one component was oriented in correspondence with the orientation of the eye, while the other component was normally oriented. Histological analysis and observations on genetically marked grafts indicated that the component parts of the compound eye were of dual cellular origin. The component giving the rotated (or translocated) map belonged to the originally operated eye tissue; whereas the component giving the normally oriented map was derived from newly grown eye tissue coming from the optic stalk. In no case was a normally oriented map obtained from a rotated or translocated eye. The results are discussed in relation to mechanisms proposed to account for the determination of map-related retinal specificity.


The target tissue of limb-bud polarizing activity in the induction of supernumerary structures.

When polarizing mesoderm from the posterior border of the 4-day chick limb bud is placed adjacent to anterior limb mesoderm and ectodermal ridge, the anterior ridge thickens and mesodermal outgrowth ensues, resulting in supernumerary limb structures. This apposition of anterior and posterior limb tissues can be accomplished by cutting off the apical one third of the limb bud and reimplanting it on the stump with its anteroposterior axis reversed. The preaxial response to polarizing activity can be obtained after only 12--18 h in the reoriented position. Reversed apical mesoderm develops supernumerary digits when combined with untreated ectoderm. The reciprocal combination, reversed ectoderm and untreated mesoderm, fails to develop supernumerary structures. We have interpreted this as evidence that, in inducing supernumerary limb structures, polarizing activity acts only on the mesoderm.


Palate morphogenesis. IV. Effects of serotonin and its antagonists on rotation in embryo culture.

Previous studies have localized non-muscle contractile systems in the posterior (region 2) and the anterior (region 3) ends of mouse palates at the time of shelf movement. In order to determine whether these contractile systems function in shelf rotation, effects of pharmacologic agents have been analyzed in embryo culture. First, it was shown that the posterior end of the palate rotates before the anterior end, and its rotation in culture was proportionally greater as development of the embryo progressed. Generally, the posterior end of the palate was more easily inhibited in embryo culture than the anterior end. Serotonin at 10(-8) M to 10(-5) M was shown to significantly stimulate rotation at the anterior end of the palate after 2 h in embryo culture. The effect on the posterior palate was less pronounced. To investigate further the role of this neurotransmitter on palate shelf rotation, serotonin antagonists were employed. Methysergide (10(-4) M) inhibited anterior shelf rotation to 12% of control values (P less than 0.005), while not significantly affecting the posterior end. Ergotamine (10(-6) M) significantly inhibited the stimulation induced by 10(-5) M serotonin (P less than 0.025). Cyproheptadine (10(-9) M) partially inhibited anterior and posterior shelf rotation in embryo culture. When injected into the pregnant dam, cyproheptadine partially inhibited shelf rotation and fusion. The palate was examined histologically after embryo culture. In the presence of 10(-4) M methysergide, the elongated contractile cells in region 3 at the anterior and midpalatal mesenchyme were prevented from rounding. Thus, serotonin may be regulating rotation of the anterior end of the palate by an effect on cell-mediated process.


Reversible inhibition of chondrogenic expression by certain hyaluronidase preparations.

Embryonic chick chondrocytes were cultured in the presence or absence of different preparations of testicular hyaluronidase. This treatment inhibited the accumulation of cartilage matrix as indicated by phase-contrast microscopy, by Alcian green staining, and by accumulation of 35S-labeled material. In addition, most preparations of testicular hyaluronidase caused a conversion of the cells to a fibroblastic phenotype characterized by a faster growth rate and the synthesis of type-I collagen. This effect was found to be concentration-dependent and was not observed at the minimum concentration of hyaluronidase required to inhibit matrix accumulation. Since two more highly purified hyaluronidase preparations prevented matrix accumulation but did not cause the fibroblastic transformation, it is likely that the conversion to a fibroblastic phenotype is caused by a contaminant in the other hyaluronidase preparations.


The development of interlimb co-ordination during swimming in postnatal rats.

The postnatal ontogeny of interlimb co-ordination was studied in rats from day 1 after birth to day 22. Swimming rather than walking was studied in order to minimize any effect of weak limb muscles in very young rats. Videotape records of swimming were analysed on a frame-by-frame basis to determine stroke cycle duration for individual limbs and interlimb latency and phase relationships. Interlimb co-ordination typical of swimming (or trotting) in adult quadrupedal vertebrates was already present on postnatal day 1, and so apparently the neural pattern generating circuitry for this behaviour is already established by this stage. In young rats it was possible to see 1 limb, or almost any combination of 2, 3 or 4 limbs, moving during swimming, and usually with proper phase relationships. This suggests that each limb has its own separate neural pattern generator and that there are effective interlimb co-ordinating mechanisms controlling moving limbs during swimming, even at very early stages. There was a gradual decrease in stroke cycle duration (increase in frequency) during the first two postnatal weeks. This may be due to maturing sensory input.


Non-simultaneous auditory masking in the goldfish, Carassius auratus.

Auditory thresholds were determined for 500 HZ pure tone pulses of 15, 25 and 50 ms duration presented leading, following or simultaneously with noise pulses of 50 or 250 ms duration. Masking by the noise decreased: (i) with an increase in tone pulse duration; (ii) with a shortening of the noise pulse duration; and (iii) as the interval between tone and noise pulses was increased from 0 to 350 ms. The effect of the noise was independent of whether the noise led or followed the pure tone. It is suggested that the most significant factor affecting masking was the duration of the interval between tone and noise, and that the site for the interactions between signals is central to the inner ear.


Behavioural and physiological aspects of swimming in cercariae of the digenetic trematode, Proterometra macrostoma.

1. Cyclical swimming behaviour of the cercariae of the digenetic trematode, Proterometra macrostoma, involves a highly regular alternating swim-sink sequence. During periods of swimming the cercariae are propelled upward through the water by alternating lateral contractions of the tail. Following each burst of swimming the cercariae passively drift downward. 2. Suction electrode recordings from the tail during swimming reveal that a single biphasic potential precedes each contraction in a burst. 3. The site of initiation of the rhythmic activity is the transverse band at the junction of the furcae and body of the tail. Sensory feedback does not play a major role in maintenance of the rhythm. 4. A burst of swimming can be initiated by tactile stimulation of the tail. At no time is a cercaria refractory to tactile stimulation. 5. The tail of P. macrostoma cercariae is an autonomous locomotor organ specialized for the brief free-living period between emergence from the snail host and infestation of the primary host.


Cinematographic and electromyographic analysis of vertical standing jump in the dog.

The electromyograms of 37 skeletal muscles were obtained using the bipolar wire electrode method in the vertical standing jump of a dog. Their electromyographic patterns were analyzed in conjunction with cinematographic films. Co-contraction of muscles of the extremities was observed during take-off and landing. Electromyograms also revealed that the forelimbs were accelerated against the body just after take-off and that the fore quarters transferred the centre of gravity of the body in a much more complicated movement than the hind quarters. In the floating phase, the muscles of the lower extremities had no activity, apart from some proximal ones. That the muscles of the four extremities exhibited their activity just before landing indicates that the activity may have been controlled by a central programme. In the vertical standing jump, the dog brings the centre of gravity of the body near to the kicking or landing paws by skillful movement of the axial skeleton. Cinematography revealed that, in the leaping gallop gait, the dog makes a similar movement of its axial skeleton.


Neurophysiological correlates of the dopaminergic cilio-inhibitory mechanism of Mytilus edulis.

The neurophysiological regulation of gill ciliary activity by the CNS of the bivalve mollusc Mytilus edulis was studied by recording electrophysiological activity of the branchial nerve while simultaneously observing ciliary activity of the lateral ciliated cells of the gill by stroboscopic microscopy. The addition of dopamine to the visceral ganglion slowed and stopped ciliary activity by increasing the firing rate of the cilio-inhibitory dopaminergic neurones of the visceral ganglion which innervate the gill. This could be antagonized at the ganglion by pre-applications of ergonovine or methysergide, or by prior treatments of intact animals with the neurotoxin 6-hydroxydopamine. The study confirms earlier work showing the inhibitory functioning of dopaminergic neurones of the CNS and demonstrates the manner in which they may exert their effects.


Pharmacological properties of axonal sodium channels in the cockroach Periplaneta americana L. I. Selective block by synthetic saxitoxin.

Voltage-clamp experiments on isolated giant axons of the cockroach Periplaneta americana L. show that chemically synthesized saxitoxin specifically and reversibly blocks the transient inward sodium current without affecting the steady-state outward potassium current. From the concentration depending of sodium current suppression it is concluded that individual sodium channels are blocked by single molecules of synthetic saxitoxin which bind reversibly to part of the channel with a dissociation constant of 3.0 x 10(-9) M. Synthetic saxitoxin blocks sodium channels in cockroach axons at a lower concentration than tetrodotoxin. Sodium channel block by synthetic saxitoxin is more readily reversed than tetrodotoxin-induced block.


Development of acetylchilinesterase during embryogenesis of the ascidian Ciona intestinalis.

We have characterized the embryonic muscle cell cholinesterase of the solitary ascidian, Ciona intestinalis (L.). The effects of selective enzyme inhibitors and the inhibition of enzyme activity at high concentrations of substrate suggest that the muscle cell enzyme is an acetylcholinesterase (E.C. 3.1.1.7). After gastrulation and before hatching, acetylcholinesterase activity increased 35- to 40-fold; after hatching (18 hours postfertilization) this activity continued to increase, leveling off at about 36 hours of development. Histochemical observations showed that before hatching acetylcholinesterase  was located principally in the muscle cells of the tail and, after hatching, it began to develop in cells of the adult musculature and brain. Inhibition of protein syntnesis by puromycin and of RNA synthesis by actinomycin D, suggest that both protein and RNA synthesis were required for the increase in acetylcholinesterase activity observed in unhatched embryos. Although the continued increase in enzyme activity duirng embryonic development was sensitive to puromycin at all times tested, the actinomycin D sensitivity of this increase was restricted to a discrete time that was completed by about 11 hours of development.


Calcium-induced dehiscence of cortical granules in Xenopus laevis oocytes.

Microinjection of 0.1 microgram of Ca++ into Xenopus laevis oocytes induces breakdown of the cortical granules. The cortical granules disappeared in both full grown (Stage VI) and small growing (Stage IV) oocytes. Microinjection of Mg++, K+, or Na+ had no effect on cortical granules in either Stage IV or Stage VI oocytes. Small quantities (0.03 microgram) of Ca++ induced dehiscence of the cortical granules only in proximity to the injection site.


Pigment synthesis in the Himalayan mouse.

The effect of temperature on pigment synthesis in adult and juvenile Himalayan mice was investigated. Since pigment synthesis only occurs in actively growing hair, adult mice were plucked to induce hair growth. The extent of darkening of the hair was recorded by photography against a reference scale. The presence of pigment granules in hair follicles was investigated histologically. Housing adult and juvenile mice at 15 degrees C results in the synthesis of pigment in growing hair follicles whereas housing at 30 degrees C results in the absence of pigment granules in the growing hair follicles.


Injection of sperm heads into immature rat oocytes.

When sperm heads are injected into rat oocytes at the germinal vesicle stage the sperm heads remain intact until the germinal vesicle breaks down. Then they decondense but do not form pronuclei. This observation agrees with the results reported for in vitro fertilization of immature oocytes from rats, mice and hamsters.


Lizard and newt tail regeneration: a quantitative study.

Almost perfect fits of the Gompertz equation to the growth in length of tail regenerates in the lizard, Lacerta lepida, and the newt, Notophthalmus viridescens, were obtained. Comparison of certain parameters of the equation with published mitotic index data suggests that the Gompertz equation characterizes each system at least from the time that significant mitotic activity is first observed histologically. An objective method for comparing the regeneration periods of the two species is described and applied. A unified hypothesis derived from consideration of properties of the Gompertz equation successfully accounts for the following phenomena reported, but previously unexplained, in the literature: (1) proximal amputations result in longer regenerates than do distal amputations; (2) proximal amputations elicit greater absolute rates of elongation (in mm/day) than do distal amputations; (3) the percent replaced of the length removed is rather constant, regardless of the absolute length regenerated; and (4) one of the parameters of the Gompertz equation appears to be lognormally distributed in a regenerating population. (See text for references.) A computerized interactive graphical system for normalizing growth equations of individual regenerates and integrating the mathematical model with potential candidates for biological control factors is briefly described.


Acute and chronic hypoxia in rats. I. Effect on organismic respiration, mitochondrial protein mass in liver and succinic dehydrogenase activity in liver, kidney and heart.

The objective of this investigation was to characterize organismic, organ and mitochondrial alterations in rats over the course of 27 days at 0.4 atm. In the adjustment phase (day 1 through 5) a significant decrease in systemic oxygen uptake and body weight (23% of pre-altitude values) occurred. In the acclimating state (day 7 to 27) body weight was regained but oxygen consumption remained depressed. Hematocrit increased hyperbolically from 45% in 0-day rats to 79% in 27-day rats. Liver, kidney and heart weights and total organ protein paralleled the changes observed in body weight. Total organ succinic dehydrogenase activity showed a wave-like oscillation for liver and kidney; activity was decreased in both organs by day 5, showed a transient but significant increase on days 16 through 18 and a return to diminished activity on day 27. Succinic dehydrogenase activity for heart became depressed in the adjustment phase but showed a stable level comparable to pre-altitude values in the accliminating phase, days 7 through 27. Liver mitochondrial protein mass was unchanged from pre-altitude values on days 5 and 27 even though succinic dehydrogenase activity was significantly depressed. Therefore, the changes in succinic dehydrogenase activity are not representative of altered mitochondrial mass but suggest that mitochondrial function was altered.


Interactions between normal and pigment cell populations mutant at the dominant-spotting (W) and steel (Sl) loci in the mouse.

Through the use of dermal-epidermal recombination methods a competition between mouse embryo melanoblasts of the genotype Wv/w C/C, w/w c/c, Sld/sl C/C and sl/sl c/c was established. Control combinations were made between C/C and c/d components. The extent of pigment found in hair of grafts after three weeks growth in mouse testes was used as evidence of an interaction between populations. Normal and albino melanoblasts were found to be similar in viability, whereas melanoblasts of the genotype Wv/w C/C were largely excluded from hair follicles when placed in competition with w/w c/c melanoblasts. No difference in competitive advantage was observed between Sld/sl C/C and sl/sl c/c populations. These results confirm that the W and sl loci act at different sites. In addition they suggest that Wv/w melanoblasts are marginally viable cells that cannot compete with normal melanoblasts when the popuolations interact. The Wv/w melanoblast failure can also explain the spotting pattern and pigment dilution characteristic of dominant-spotting heterozygous mice.


Ultrastructural changes in cells associated with interkinetic nuclear migration in the developing chick neuroepithelium.

Changes in fine structure of cells associated with interkinetic nuclear migration in the developing chick neuroepithelium were investigated. Interphase cells are elongated and span the entire thickness of the neuroepithelium. As cells round up in preparation for mitosis, they sever their contacts with the basement membrane, but retain their apical junctions. Meanwhile, microtubules lose their apico-basal orientation and the apical microfilament bundle relaxes to allow broadening of the luminal surface. These changes in the cytoarchitecture together with an increased cytoplasmic viscosity may cause rounding of mitotic cells and their juxtaluminal position. Mitotic cells remain at the lumen from late prophase through early telophase. By late telophase, daughter cells start to elongate toward the base of the neuroepithelium. The ultrastructural changes during elongation recapitulate, in a reverse order, the events of rounding up in preparation for mitosis. Daughter cells are connected for some time after mitosis by a thread of cytoplasm. The thread is filled with microtubules representing a remnant of the spindle complex and has an electron-dense midbody at about the middle of its length. During the final stage of separation of daughter cells, the thread is split at the level of the midbody.


Fast and slow steps in the activation of sodium channels.

Kinetic features of sodium conductance (gNa) and associated gating current (Ig) were studied in voltage-clamped, internally perfused squid axons. Following a step depolarization Ig ON has several kinetic components: (a) a rapid, early phase largely preceding gNa turn-on; (b) a delayed intermediate component developing as gNa increases; and (c) a slow component continuing after gNa is fully activated. With small depolarizations the early phase shows a quick rise (less than 40 mus) and smooth decay; the slow component is not detectable. During large pulses all three components are present, and the earliest shows a rising phase or initial plateau lasting approximately 80 mus. Steady-state and kinetic features of Ig are minimally influenced by control pulse currents, provided controls are restricted to a sufficiently negative voltage range. Ig OFF following a strong brief pulse also shows a rising phase. A depolarizing prepulse producing gNa inactivation and Ig immobilization eliminates the rising phase of Ig OFF. gNa, the immobilized portion of Ig ON, and the rising phase reappear with similar time-courses when tested with a second depolarizing pulse after varying periods of repolarization. 30 mM external ZnCl2 delays and slows gNa activation, prolongs the rising phase, and slows the subsequent decay of Ig ON. Zn does not affect the kinetics of gNa tails or Ig OFF as channels close, however. We present a sequential kinetic model of Na channel activation, which adequately describes the observations. The rapid early phase of IgON is generated by a series of several fast steps, while the intermediate component reflects a subsequent step. The slow component is too slow to be clearly associated with gNa activation.


Magnesium content and net fluxes in squid giant axons.

The Mg content of axons freshly dissected from living specimens of the tropical squid Doryteuthis plei was determined by atomic absorption spectroscopy to be 4.2 +/- 0.2 mmol/kg axoplasm. The axon's ability to maintain this physiological content of total intracellular Mg([Mg]i) was studied. Mgi was shown to be a linear function of Mgo when Mgo of incubating fluid was varied between 0 and 250 mM. When Mgo = 15 mM, Mgi was found to be the same in incubated fibers as in fibers freshly dissected. Mgi levels were unaffected by depolarization of the membrane by high Ko. Stimulation resulted in an extra influx of Mg of 0.05 pmol/(cm2 . impulse) when Mgo = 55 mM. Mgi was found to be a complicated function of the concentration of extracellular Na or Li (Xo), which was substituted for Tris. With 385 mM Lio the Mgi level was found to be 2.5-fold larger than the level observed with 385 mM Nao after incubation for 3 h. The function relating Mgo to Xo was qualitatively unaffected in axons poisoned with the mitochondrial uncoupler carbonyl cyanide, p-trifluorome-thoxy-phenylhydrazone (FCCP) and the inhibitor of glycolysis, iodoacetic acid (IAA); the absolute levels of Mgi, however, were some 30% higher in the poisoned axons at all [X]o explored. 2 h incubation of axons in a 333 mM Mg, 40 mM Li solution increased Mgi 3.5-fold in control axons and 5-fold in poisoned axons. These Mg-loaded axons were able to recover physiological levels of Mgi with a half-time of 3-5 h only if kept in a solution which contained Na (220 mM) regardless of whether the axons had been inhibited with FCCP + IAA. Therefore, it may be concluded that the physiological Mgi concentration can be maintained by the Na electrochemical gradient, even when the axon is metabolically poisoned.


Facial asymmetries: problems in genetic counselling.

The nosology of the facial asymmetries was studied and illustrated by 4 personal cases: two of incomplete oculo-auriculo-vertebral dysplasia, one of probable Saethre-Chotzen syndrome and one of Klippel-Trenaunay-Weber syndrome. Hints for the recurrent risk counselling are given.


[Pseudodiastrophic dwarfism: a case report].

On the occasion of one new possible observation of the pseudodiastrophic dworfism observed in a femal newborn, first child of young, non-consanguineous parents, authors discuss the differential diagnosis as well as the problem of genetic counselling in the present case since the child's father is a technician in radiology and exposed to X-rays during 7 years.


[Exclusion of MNSS, Kidd and Gm from the extreme end of the short portion of chromosome 8].

11 blood and seric group markers were studied in a case of 46,XX,del(8)(qter yields p22 :) in order to contribute to the exclusion map. MNSs and Jk are informative and could be excluded from the region. The proband is also definitly heterozygous for immunoglobulin Gm groups which were tentatively assigned to the short arm of chromosome 8 or 12.


[Omphalocele: hereditary disease with dominant transmission?].

The authors report a familial case of exomphalos affecting a mother and her daughter; they discuss the possibility of a dominant transmission.


Interaction of hepatitis B surface antigen with polymerized human serum albumin.

HBsAg binds to a solid-phase adsorbent consisting of polymerized human serum albumin (HSA) on glass particles. Both AD and AY antigenic subtypes of hepatitis B surface antigen (HBsAg) display this interaction. In either case, the binding to polymerized HSA is reduced in the presence of human serum, suggesting significant attachment of serum components at the locations on HBsAg particles where polymerized HSA binds. The temperature dependence of the interaction goes through a maximum above room temperature, in contrast to the increasing reaction with temperature of the HBsAg--anti-HBs antibody system. The interaction between HBsAg and polymerized HSA is discussed in relation to previous findings of HSA polymers and anti-polymerized albumin antibodies in hepatic patients. A mechanism for production of an autoimmune, antialbumin antibody condition, in association with hepatitis B virus infection is proposed.


Cryptic association of e antigen with different morphologic forms of hepatitis B surface antigen.

When highly purified HBsAg particles, separated by rate zonal centrifugation into populations differing in predominant size, were tested for HBeAg, the e1 specificity was detected preferentially in association with particle fractions containing large filaments and Dane particles. These results were obtained both by agar gel diffusion and by radioimmunoassay for e antigen. The e antigen activity present in these fractions was potentiated by prior treatment of particles with Tween 80, suggesting cryptic localization of e1 specificity within or under the outer membrane. The HBeAg released by detergent treatment from a purified preparation composed predominantly of small-particle forms of HBsAg was separated by electrofocusing into a peak of nonparticulate e antigen in the pH range of 5.7--6.0. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed three major polypeptides in this preparation with approximate molecular weights of 25,000, 55,000, and 70,000. Furthermore, two additional peaks of e antigen activity were detected which migrated in association with HBsAg particles at isoelectric points of 4.4 and 5.5--5.6. The major portion of e antigen remained in association with particles after further purification by rate zonal centrifugation.


Immunoglobulins to tick-borne encephalitis in the cerebrospinal fluid of man.

Antibodies of IgM and IgG type were detected in the CSF of patients with recent tick-borne encephalitis (TBE) by means of ELISA. No false-positive results were obtained with CSF specimens from patients suffering from meningitis or other illnesses. The ratio of the antibodies in serum to CSF clearly indicated that both IgM and IgG antibodies were produced in the brain itself. In patients who had previously suffered from TBE now with a different inaseptic meningitis, TBE antibodies could also be detected in CSF but only of the IgG class. Again the serum-to-CSF antibody ratio indicated that the antibodies were produced within the central nervous system. For routine diagnosis the micro-ELISA method was found to be useful; antigen-coated plates can be stored as long as three months at +4 degrees C.


Indications of anticonvulsant plasma levels monitoring in medical and surgical treatment of epilepsy.

The results of long-term (19-21 months) intensive anticonvulsant plasma levels monitoring in two patients with partial complex epilepsy resistant to therapy are reported. In the first case the qualitative and quantitative therapeutic adjustment based on the monitoring data caused the disappearance of the seizures. In the second case, in which a right mid-temporal calcification (abscess) was demonstrated by CT-scan, the attacks were not controlled by different drugs. The patient became seizure-free after a right temporal lobectomy. The importance of long-term anticonvulsant plasma levels monitoring in partial complex epilepsies unresponsive to pharmacological therapy is discussed in detail in view of possible surgical treatment.


Renal cortical imaging and the detection of renal mass lesions.

Tc-99m gluceptate renal imaging was compared with the intravenous urogram in 41 patients. While the specificity of the examination was essentially the same for both techniques, the sensitivity for the detection of renal mass lesions was better with gluceptate imaging. The study suggests the desirability of a shift in emphasis from the IVU to the Tc-99m gluceptate scintigram in the early evaluation of suspected renal mass lesions, and merits further clinical evaluation.


Anterior neck abscess masquerading as acute suppurative thyroiditis.

Two patients with extrathyroidal anterior neck abscesses are discussed. Normal thyroid scans ruled out acute, suppurative thyroiditis.


The dysraphic state of the posterior fossa. Clinical review of the Dandy-Walker syndrome and the so-called arachnoid cysts.

The Authors report their case material concerning some basic items of the dysraphic pathology of the Posterior Fossa: 22 cases of Dandy Walker syndromes (DWS) and "Arachnoid Cysts" (PFC). The mean clinical findings (predominant involvement of the vestibular structures of the brain stem in the DWS, frequent epileptic seizures and some cases of hypothalamic disturbances in the PFC) are discussed in the light of current embryological theories on Weed's "area membranacea". Finally the results of differential surgical treatments are examined: good or satisfactory results were obtained with shunts, while still debatable seems to be the direct surgical approach.


Scintillation-proximity assay of antigen-antibody binding kinetics: concise communication.

Tritiated latex particles and scintillant latex particles have been covalently coated with an antigen (human albumin) and both types of particles are than combined in dilute aqueous suspensions. The formation of antibody-induced dimer and higher-order aggregation resulted in scintillations that could be measured in a standard liquid-scintillation counter, energy-gated for H-3. Rabbit anti-human antiserum was easily detected at a titer of 1:10(6). Human albumin, in the inhibition mode, was also easily detected at 0.1 ng/ml. Since the samples are nondestructively assased, it was possible to examine the kinetics of aggregation under a variety of conditions.


The phenomenon of ipsilateral innervation. One case report.

A patient with an anterior communicating artery aneurysm successfully treated surgically by occluding its major feeding vessel, the left anterior cerebral artery, displayed a homolateral hemiparesis. The possibility of ipsilateral innervation is strongly suggested based on clinical grounds and the post operative follow-up angiographic studies, EEG and PEG.


A study of the relationship between chemical structure and bone localization of Tc-99m diphosphonic acids: concise communication.

The study was undertaker to evaluate the effect on bone localization of substitutions at the bridge carbon atom of methylenediphosphonic acid. Two monosubstituted compounds (ethylidenediphosphonic acid and benzylmethylenediphosphonic acid), and one disubstituted compound (isopropylidenediphosphonic acid), were synthesized. The biological behavior was compared with that of MDP and dichloro-MDP in the rat, using Tc-99m as a label. Ethylidenediphosphonic acid showed the highest femur-to-liver and femur-to-muscle ratios. MDP exhibited a slightly faster blood clearance than ethylidenediphosphonic acid.


In vivo labeling of red blood cells with Tc-99m with stannous pyridoxylideneaminates.

Several stannous pyridoxylideneaminates were evaluated as stannous ion sources for the in vivo labeling of red blood cells (RBCs) with Tc-99m. In spite of a considerable variety of stannous preparations, rapid and efficient RBC labeling was obtained with each stannous chelate. These results suggest that the role of the ligands is merely to stabilize the divalent state of the tin. The optimal time interval between Sn(II) and 99mTcO4- injections, and the best stannous-ion concentration, was found using stannous pyridoxylideneisoleucine (Sn-P.isoL). Maximal in vivo labeling of the RBCs was obtained with an i.v. dose of 10-20 micrograms Sn(II)/kg of Sn-P.isoL followed 15-30 min later by i.v. administration of pertechnetate.


Scintillation-camera simulator for remote-data acquisition testing.

A device based on an 8080 microprocessor was assembled for the generation of image data in a manner similar to that of the scintillation camera. This "simulator" thus permits testing of the integrity of systems for the acquisition of data over long transmission lines, without tying up the portable scintillation camera. The simulator has improved the reliability of remote-data collections and has increased the efficiency of utilization of the camera.


A new container geometry for better sensitivity in radiometric measurements.

A new two-compartment liquid scintillation vial system for radiometric measurement has been evolved, such that the light attenuation by the inner vial is minimized. The increase in relative efficiency is over 70% better than in an earlier design. The system is compact and versatile, and is suitable for automated, cumulative, or continuous radiometric measurements.


A study of age-dependent changes in thyroid function tests in adults.

Total serum thyroxine (T4), triiodothyronine (T3), T3 resin uptake (T3U), thyrotrophin (TSH), and reverse T3 (rT3) were measured in 209 healthy adults 20--89 yr old. Mean T4 values for men were stable throughout life, but in females under age 60, T4 values were significantly higher than in older women. Values for T3U in males were significantly higher than in females throughout all decades, although females had a significant increase in T3U after age 60. TSH values increased significantly in females over age 60. Throughout all decades, males had stable TSH levels that were slightly higher than the female results before age 60 and lower thereafter. Mean serum T3 declined similarly for both sexes with increasing age, although not to the extent previously reported. Men had significantly higher mean rT3 values over all decades than females, although female rT3 levels decreased after age 50 whereas males maintained stable values. The physiologic reasons for these findings may be due to sex-related changes in binding proteins and alterations in metabolic clearance rates, production, and degradation of these hormones with increasing age.


The normal dexamethasone-suppression adrenal scintiscan.

To establish the parameters of adrenal imaging under dexamethasone suppression (DS), 18 normotensive, normal male volunteers underwent dexamethasone-suppression adrenal scintiscanning. Five control groups were established and given dexamethasone, either 8 mg for 2 days or 4 mg for 7 days before 6 beta-[131I]iodomethyl-norcholesterol (NP-59) administration. NP-59 was given in doses of 2, 1, or 0.5 mCi. Early visualization (3--5 days) of the adrenals was noted in the groups on the 8 mg DS regimen with either 1 or 2 mCi of NP-59. Late visualization (5--7 days) was noted in the groups that received 4 mg DS and either 2, 1, or 0.5 mCi of NP-59, respectively. The normal adrenal will demonstrate uptake of NP-59 under DS, and the duration of DS before imaging is the critical factor as to when discernible adrenal visualization will occur. The documentation of the noraml suppression interval on these DS regimens provides a basis for the correct diagnostic interpretation of adrenal hyperfunction as seen on the dexamethasone-suppression NP-59 adrenal scan.


Partition of thallium-201 in isolated myocardial tissue of rats previously injected at rest or after exercise.

The kinetics and distribution of TI-201 in isolated myocardial tissue of rats injected i.v. with this radionuclide are compared at rest and after exercise (2 hr of forced swimming). At 1/2 and 3 hr after injection, a myocardial segment was obtained and subjected to continuous washout with the radioactivity remaining in the tissue recorded each 10 sec for 1 hr. Altogether there were four groups of ten animals each. A three-compartment model (extracellular, main intracellular, and subcellular) was found to describe adequately the kinetics of TI-201. In the groups studied 1/2 hr after TI-201 injection the most dramatic effect of exercise was a translocation of TI-201 into the subcellular compartment. The change was also present but less marked in samples from exercised rats obtained 3 hr after TI-201 injection, which suggests a transition to the resting stage. The findings suggest the possibility of structural subcellular differences in myocardial uptake for TI-201 in clinical images visualized after exercise and at rest.


A study of irradiated bone: I. histopathologic and physiologic changes.

Histologic and tracer techniques were used to investigate and document alterations in bone pathophysiology subsequent to irradiation of the left hind limb of rabbits. Numerous time-dependent changes were observed. Among these were an inflammatory response shortly after irradiation, and an increase in the remodeling of cortical bone, which peaked between 3 and 6 mo after irradiation. The changes in bone remodeling correlated with changes in vascular patency in a manner consistent with the hypothesis that radiation damage in mature bone is mediated primarily through alterations in the fine vasculature. The findings of this study provide important information on the time course of changes in bone pathophysiology following regional irradiation. They are used in the second of this series of papers to help establish which mechanisms are responsible for postirradiation alterations in the localization of Tc-99m pyrophosphate in these rabbits.


Studies of skeletal tracer kinetics: II. evaluation of a five-compartment model of [18F]fluoride kinetics in rats.

We have evaluated a five-compartment model of [18F]fluoride kinetics in rats. The initial fluoride distribution was found to be similar to that of [77Br]bromide, a known extracellular-fluid (ECF) tracer, in agreement with the hypothesis underlying the model, and the measured uptake rate in rat bones compared well with the digital computer solution. Simpler models did not give a better fit. In dead rats, fluoride movement was found within the skeleton, presumably from bone ECF to bone substance, although not as rapidly as predicted or found in the live animal. Evaluation of the rate constants permitted estimates to be made of cardiac output, skeletal blood flow, and bone ECF volume, all in accord with independent measurements. It is suggested that skeletal blood flow at rest is a constant fraction of body weight, and probably subserves a hematopoietic as well as a mineralization function.


In vivo measurement of body nitrogen by analysis of prompt gammas from neutron capture.

A method for the in vivo determination of body nitrogen by prompt gamma photons from neutron capture is described. An 85-Ci 238Pu-Be source provides the neutrons. The gamma detection system consists of two 15.24 x 15.24 cm Nal(TI) detectors placed above the patient. Absolute value of body nitrogen is determined using body hydrogen as an internal standard. The reproducibility of the method is +/- 3% for a body dose of 26 mrem.


Cerebral venous angioma: correlation of radionuclide brain scan, transmission computed tomography, and angiography.

Three cases of intracerebral venous angioma, a rare vascular malformation, were studied by radionuclide brain scan, transmission computed tomography (TCT) and angiography. In each case, the radionuclide flow study demonstrated a typical area of abnormal increase in activity during the venous phase; in two of the cases the arterial phase was also abnormal. Each contrast angiogram demonstrated a normal arterial distribution and a characteristic network of abnormal veins that converged to a large transcerebral draining vein. The TCT scans showed enhancing, curvilinear densities; while not specific, this finding should suggest the possibility of venous angioma in the brain.


Tantalum-178-labeled agents for lung and liver imaging.

Despite its 9.3-min half-life, Ta-178 can be used to produce radiopharmaceuticals for lung and liver imaging. A variety of human serum albumin microspheres and other particulate radiopharmaceuticals were labeled with Ta-178. A period of approximately 10 min was required for their preparation and administration to rats. Extrapolation to the clinical situation suggests that imaging could take place after one half-life of the nuclide has elapsed. We found that satisfactory imaging is possible using Ta-178 radiopharmaceuticals with the Anger camera and a pinhole collimator. Since short imaging times, high spatial resolution, and low patient doses are reasonable objectives in pediatric scintigraphy, these new radiotracers may prove useful for lung and liver imaging in children.


Membrane transport of Tc-99m-labeled radiopharmaceuticals, I. Brain uptake by passive transport.

The membrane transport properties of twelve Tc-99m complexes were studied by determining each complex's brain uptake index (BUI), extent of protein binding, and octanol-to-saline partition coefficient. The chelating agents used were classified as either N-substituted carbamoylmethyliminodiacetates, substituted oxines, N,N'-diesters of EDTA, or N-substituted derivatives of DTPA. The Tc-99m complexes were found to cross the blood--brain barrier in proportion to their lipophilicity. Of the four types of chelating agents tested, substituted oxines appear to be most suitable for the development of diffusible Tc-99m-labeled compounds for imaging nonexcretory organs.


In vivo distribution of Tc-99m(Sn)pyridoxylideneisoleucine: effects of storage and labeling conditions. Concise communication.

Various conditions for the storage of the stannous pyridoxylideneisoleucine (Sn-P.isoL) kit reagent, and also for the preparation of Tc-99m(Sn)P. isoL, have been evaluated experimentally using rats. Both the frozen (-30 degrees C) and the freeze-dried state were found to be suitable for storage of the kit reagent. For the labeling procedure, at least 40 min incubation time (Sn-P.isoL + 99mTcO4-) was necessary at room temperature, but the same superior results could be obtained quickly by heating the mixed solution for 2 min in a boiling-water bath. The pertechnetate could be added in a volume up to four times that of the kit reagent. MoVI) and/or AI(III) in the pertechnetate solution did not interfere with the formation of Tc-99m(Sn)P.isoL up to the highest tested concentration of 40 micrograms/ml each.


Correction for out-of-focal-plane blurring in a simulated multiplane tomographic scanner.

A technique has been developed to remove out-of-focal-plane blurring from coronal and axial images made using a multiplane tomographic scanner. The technique uses a combined smoothing and differential operator that is applied to the axial images. It has been tested using computer-simulated images, with favorable results. The usefulness of the technique in a real system has yet to be determined.


Use of technetium-99m as a radioactive label to study migratory patterns of leukocytes.

Technetium-99m had been used as a radioactive label to study the migratory patterns of neutrophils. In a previous in vitro study, neutrophils were labeled with Tc-99m and infused into patients with and without various hematological disorders. Increased pulmonary localization was detected by scintillation camera within 10 min; this decreased gradually within 3 hr. Accumulation was seen in the liver and spleen at 3 hr. The same results were noted by using neutrophils labeled with Tc-99m sulfur colloid. In a patient with severe ulceration in the oral cavity, due to acute leukemia, Tc-99m-labeled transfused neutrophils that were collected by filtration leukopheresis were concentrated in the infected lesions.


Myocardial imaging with thallium-201: the controversy over its clinical usefulness in ischemic heart disease.

Several uses of thallium myocardial imaging (assessment of questionable stenosis and detection of infarction) provide unique information and are useful adjuncts in the diagnostic workup and treatment of patients with coronary artery disease. Screening studies with thallium to detect the presence or absence of coronary artery disease have generated considerable controversy. Much of this conflict can be resolved by a careful analysis of the purpose of the screening study, the sensitivity and specificity of the imaging test, and the prevalence of disease in the subgroup under study. With the principles outlined, thallium imaging can be used to make patient-care decisions with a reasonable degree of confidence.


The appearance of bone scans following fractures, including immediate and long-term studies.

Bone scans were performed on 204 patients at intervals ranging from 6 hr to several years after traumatic fractures. The minimum time for a bone scan to become abnormal following fracture was age-dependent; however, 80% of all fractures were abnormal by 24 hr, and 95% by 72 hr, after injury. Three distinct temporally related phases were noted on bone scans as sequential studies showed a gradual return to normal. The minimum time for a fracture to return to normal on a bone scan was 5 mo. Approximately 90% of the fractures returned to normal by 2 yr after injury.


The significance of augmented radiocolloid uptake by the spleen in patients with malignant melanoma.

Increase in splenic uptake of Tc-99m sulfur colloid was noted in 47 of 147 (32%) patients with cutaneous malignant melanoma early in the coure of disease. Patients with disseminated disease and/or clinical or laboratory evidence of hapatic dysfunction were excluded from study. Recurrence rate of 2 yr was higher for those patients with splenic scans demonstrating augmented uptake compared with patients having normal scans, 36% against 16% (p less than 0.02). These differences resulted from a much more favorable prognosis in women with normal scans contrasted with women with increased uptake, 6% against 26% (p less than 0.05). Women with increased splenic uptake, and all men regardless of scan status, seemed to have a higher rate of recurrence than women with normal spleen scans. Scan status may be an adjunctive prognostic marker in women.


Axillary lymphoscintigraphy by radioimmunodetection of carcinoembryonic antigen in breast cancer.

In seven women with carcinoma of the breast I-131-labeled antibodies to carcinoembryonic antigen (CEA)  were administered subcutaneously in the finger webs. Subsequent scintigraphic immages demonstrated localization of radioactivity in the ipsilateral axillary metastases of all patients and in the contralateral axillae of three. Fifteen patients with either gastrointestinal or genitourinary cancers were studied as controls; in 12 both the hands and feet were injected with antibodies to CEA and in the other three either the hands or feet. Radioactivity was observed in the inquinal nodes of four control patients with tumors below the diaphragm and in the axillary nodes of one patient with a tumor above the diaphragm. The concentration of antibody in lymph node metastases from breast carcinoma was 100% specific. In those lymph nodes that presumably contained no metastatic tumor but demonstrated localization of labeled antibody, retention of CEA in the nodes from tumor drainage is postulated as the receptor site for the antibody.


Transmission computed tomography, Tc-99m MAA scintigraphy, and plain chest radiography after experimentally produced acute pulmonary arterial occulusion in the dog.

We have occluded segmental and subsegmental pulmonary arteries in the dog with Swan-Ganz balloon catheters or i.v. injection of autologous clot, and have studied the chest with transmission computed tomography (TCT), Tc-99m-MAA gamma imaging, and plain radiographs. The arterial occlusions were between 1 and 5 hr old at the time of imaging. Radiographs revealed no lesions. Tc-99m MAA scanns revealed ten of 11 lesions. When a TCT image was made before i.v. injection of Renografin-60, two of 11 lesions were identified; after Renografin the score was four out of ten. The appearance of lesions on TCT was highly variable. Tc-99m-MAA gamma imaging, therefore, is far more accurate than TCT in the identification of small experimentally produced acute pulmonary arterial occlusions in the dog, and our study fails to suggest a secure place for TCT in the diagnosis of small, acute human pulmonary emboli. The commonly-held assumption that postembolic lung is oligemic is questioned.


Studies of skeletal tracer kinetics. III. Tc-99m(Sn)methylenediphosphonate uptake in the canine tibia as a function of blood flow.

Experiments were performed in 14 dogs to study the effect of changes in bone blood flow on the tibial uptake of the skeletal tracer Tc-99m(Sn)methylenediphosphonate (Tc-99m MDP). Aortic blood was diverted through a pulsatile-flow pump in order to monitor and control femoral arterial blood flow. Tibial nutrient perfusion, as measured with labeled microspheres, paralleled the changes in arterial flow. We found that increments in bone blood flow up to four times normal produced only minimal augmentation of Tc-99m MDP uptake (mean = 33%), a markedly nonproportional relationship. The data points clustered about a predicted curve produced by perturbing the rate constants of a seven-compartment model obtained in normal dogs. These findings indicate that bone uptake of Tc-99m MDP is diffusion-limited, and they therefore cast doubt upon the validity of a method used for many years for estimating bone blood flow, the so-called skeletal tracer clearance technique. Nerve section, performed in 14 other dogs, augmented Tc-99m MDP uptake by about 50% at supranormal flows, suggesting a parallel-flow model of the microcirculation in bone, under sympathetic control. Such a model satisfactorily explains many scintigraphic findings in disease states.


The value of the bone scan in idiopathic regional migratory osteoporosis.

Idiopathic regional migratory osteoporosis is a self-limited entity of unknown origin, which has received little attention in the nuclear medicine literature. It is characterized by severe joint pain, typically in a hip, with normal laboratory and normal early radiographic findings. Spontaneous recovery occurs, but recurrence is frequent in another joint, often the opposite hip. Recurrence in the same joint has never been reported. The bone scan is shown to be positive with first symptoms and is important in the diagnosis and management of this entity. Three cases are presented.


Diverse bone scan abnormalitites in "shin splints".

Four young patients who presented with pain over the anterior compartment of the legs, gave a recent athletic history suggesting stress fractures. Although radiographs were initially normal in all four cases, the bone scintigrams were positive. The individual findings, however, were quite different. In one there was a single focal area of increased radioactivity in each of the tibias; the second patient had uneven uptake of radiotracer and several foci of accumulation in the fibulas; the third showed diffuse linear tibial uptake suggesting periosteal lesions; and the fourth case revealed uptake in the lateral malleolus and in bones of the foot.


Biological distribution and excretion of DTPA labeled with Tc-99m and In-111.

For the purpose of radiation dose estimates, organ assays and excretion measurements of the Tc-99m and In-111 complexes with DTPA were conducted in dogs at various time intervals up to 24 hr, and the results compared with available human data. The peak concentration of the Tc-99m complex, at 3 min after injection, was 5% of the administered dose for one kidney, 3.5% for the liver, and 3.5% for the small bowel. No organ system except the urinary tract reached a concentration higher than that in blood for several hours after the injection. The biliary excretion of these agents was extremely low, and their elimination in the feces was negligible. In man, it appears that the residual 4-5% of an administered dose not eliminated in the urine by 24 hr is widely distributed in various tissues. The distribution of the In-111 complex is similar but not identical to that of the Tc-99m complex.


The low-temperature scintillation properties of bismuth germanate and its application to high-energy gamma radiation imaging devices.

Bismuth germanate is a scintillation material with very high z, and high density (7.13 g/cm3). It is a rugged, nonhygroscopic, crystalline material with room-temperature scintillation properties described by previous investigators as having a light yield approximately 8% of that of NaI(Tl), emission peak at approximately 480 nm, decay constant of 0.3 microsec, and energy resolution congruent to 15% (FWHM) for Cs-137 gamma radiations. These properties make it an excellent candidate for applications involving the detection of high-energy gamma photons and positron annihilation radiation, particularly when good spatial resolution is desired. At room temperature, however, the application of this material is somewhat limited by low light output and poor energy resolution. This paper presents new data on the scintillation properties of bismuth germanate as a function of temperature from -- 196 degrees C to j0 degrees C. Low-temperature use of the material is shown to greatly improve its light yield and energy resolution. The implications of this work to the design of imaging devices for high-energy radiation in health physics and nuclear medicine are discussed.


Absorption-edge transmission technique using Ce- 139 for measurement of stable iodine concentration.

We have investigated a technique for measuring stable iodine concentrations by absorption-edge transmission measurements using a Ce 139 radiation source. The lanthanum daughter emits characteristic x-rays whose energies just bracket the absorption edge of iodine at 33.2 keV. Relative transmission of these x-rays is sensitive to iodine concentration in the sample, but is relatively insensitive to other elements. By applying energy-selective beam filtration, it is possible to determine the relative transmission of these closely spaced x-ray energies with NaI(Tl) detectors. Optimizations of sample thickness, detector thickness, and Ce-139 source activity are discussed. Using sample volumes of about 10 ml, one can determine iodine concentration to an uncertainty (standard deviation) of +/- 5 microgram/ml with a 5-mCi source in a measurement time of 400 sec. Potential clinical applications of the in vitro technique are discussed, along with comparative aspects of the Ce-139 technique and other absorption and fluorescence techniques for measuring stable iodine.


Resolution rates of pulmonary embolism assessed by serial positron imaging with inhaled O-15-labeled carbon dioxide.

Embolic obstruction of pulmonary blood flow results in delayed regional clearance of inhaled C15O2. Focally retained C15O2 appears as zones of increased O-15 activity on serial positron scintigrams, which show the locations of occluded pulmonary segments. Inhalation of C15O2, with serial imaging by a multicrystal positron camera, was used to locate and assess the magnitude of occluded pulmonary segments in eight patients with arteriographically documented pulmonary emboli. The imaging with C15O2 inhalation was repeated after 1 wk of i.v. heparin therapy to evaluate the ability of this technique to determine resolution rates of pulmonary emboli during anticoagulant therapy. In all patients, zones of increased C15O2 activity corresponded with sites of emboli identified arteriographically. After 1 wk of continuous heparin therapy, zones of focally retained C15O2 were totally resolved in three patients, diminished in four, and unchanged in one. The regional pulmonary clearance rate of C15O2 was delayed over embolized pulmonary segments in all patients (men clearance half-time = 42.2 sec +/- 11.2 s.e.m.) and improved after heparin therapy (13.9 +/- 3.9 sec; p less than 0.05). Serial C15O2 inhalation imaging is a rapid noninvasive radionuclide technique for detection of pulmonary emboli. It can be repeated at frequent intervals to assess the resolution of emboli during anticoagulant therapy.


Early and delayed Tc-99m glucoheptonate brain scintigraphy: are routine early images indicated?

Both early and delayed Tc-99m glucoheptonate brain images were evaluated in 859 patients in order to determine whether the early imaging with this agent is clinically useful. The results suggest that the early brain images are inferior to the delayed ones in detecting CNS lesions. Use of both, however, may help to differentiate skull or scalp abnormalities from true lesions of the brain.


Radionuclide venography and lung scanning: Concise communication.

In 102 patients suspected of pulmonary embolism, we have assessed the ability of a radionuclide (emission) venogram to complement the pulmonary perfusion scintigram in establishing a diagnosis. The efficacy was compared using decision analysis and Bayes's theorem. Two criteria for a positive test were compared: Criterion 1--the test is positive if the lung scan a) indicates a high probability of pulmonary embolus, or b) is abnormal but indeterminate for pulmonary embolus; Criterion 2--the test is positive a) if the lung scan indicates a high probability of pulmonary embolus, or b) if the emission venogram is positive in a patient with a lung scan considered abnormal but indeterminate for pulmonary embolus. The use of Criterion 2 decreased the sensitivity from 100% to 95% and increased the specificity from 74% to 93%. We conclude that a simultaneous emission venogram assists in improving the specificity, accuracy, and the predictive value of a standard pulmonary perfusion study in the diagnosis of pulmonary embolus.


Survival of red blood cells in rabbits after acute administration of unlabeled stannous pyrophosphate: Concise communication.

We investigated the possibility that acute administration of unlabeled stannous pyrophosphate may adversely affect red blood cells in the rabbit. Our method was similar to the in vivo labeling of RBCs with technetium-99m for blood-pool scanning. The investigation showed that dosages recommended in the literature produce no demonstrable difference between pre- and postdose RBC survival, which strongly suggests that the stannous content of the pharmaceutical is not harmful to red blood cells.


Concentration of radiolabeled cholesterol in a feminizing adenoma of the testis.

Quantitative tissue studies demonstrated increased 19-[131I]-iodocholesterol concentration in a feminizing adenoma of the testis. The potential application of iodocholesterol and its isomers in the detection of steroid-secreting neoplasms of the testis and ovary is suggested.


An efficient, gaseous detector with good low-energy resolution for (less than or equal to 50 keV) imaging.

An imaging detector with good energy resolution and reasonable spatial accuracy has been designed for biomedical applications. It is based on a scintillating proportional gas chamber. The energy resolution is typically 5.4% (FWHM) at 27 keV and the spatial resolution is 2.7 mm (FWHM) for 22-keV x-rays. The physical processes involved in this detector are discussed along with its main limitations and merits.


A computerized rotating laminar radionuclide camera.

We have constructed a radionuclide camera that embodies a unique detector-collimator concept and provides a radically new approach to imaging. The heart of the instrument is a linear array of semiconductor detectors separated by thin tungsten plates that confine the field of view of each detector to one dimension. This collimator design has a higher collection efficiency than the standard parallel-hole collimator but cannot directly produce a two-dimensional image. When multiple measurements are taken as the array rotates through 180 degrees, a computerized image restoration algorithm can then produce two-dimensional images with resolution determined by the width of the detectors. A small prototype camera has produced images with resolution superior to conventional Anger cameras.


Thyroid scintigraphy with time-coded aperture.

Coded aperture imaging (CAI) and multiple-view pinhole imaging (MVPI) of the thyroid were compared in 19 patients to determine whether CAI's theoretical advantages of high resolution, high efficiency, freedom from distortion, accurate size representation, and tomographic presentation could be realized in the clinical setting, and to determine whether CAI offers any advantage over conventional MVPI. The coded aperture images were judged better than the pinhole images in five cases, equal in 13 cases, and worse in one case. The major problem with CAI was the long reconstruction time. Further development and an extended clinical trial appear warranted.