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PubMed2003

Process of care and preliminary outcome in limited-stage small-cell lung cancer: results of the 1995-1997 patterns of care study in Japan.

PURPOSE: To evaluate the practice process using the national average (NA); to compare differences in the process of care by age group; and to provide a preliminary outcome data for limited-stage small-cell lung cancer in Japan. METHODS AND MATERIALS: The Patterns of Care Study conducted a nationwide survey of the care process for Stage I-III small-cell lung cancer in Japan. Patients were divided into three age groups: <65 years (younger group, n = 73); between 65 and 74 years (intermediate group, n = 81); and >or=75 years (elderly group, n = 20). RESULTS: The NA for the total dose was 49.0 Gy, and for use of photon energy >or=6 MV, chemotherapy, and prophylactic cranial irradiation was 77.3%, 93.2%, and 1.69%, respectively. Age stratification had no impact on the variables of radiotherapy (RT) such as total dose and field size. Only 37% of patients received chemotherapy and thoracic RT concurrently. The proportion of patients who received chemotherapy and RT concurrently was 44%, 27%, and 25% of the younger, intermediate, and elderly groups, respectively (p = 0.029). Etoposide and cisplatin were less frequently used in the elderly group (>or=75 years old). Overall survival at 3 years for the entire group was 26%. The 3-year survival rate was 30% in the younger group, 28% in the intermediate group, and 9% in the elderly group. Variables found to have a significant impact on survival by multivariate analysis were the use of chemotherapy (p = 0.030), age (p = 0.032), and T stage (p = 0.042). CONCLUSION: Calculated NAs showed that the results of clinical study had favorably penetrated into the practice process in Japan. The results demonstrated that patient age significantly influenced the process of chemotherapy such as the use of etoposide and cisplatin for limited-stage small-cell lung cancer in Japan. More concurrent chemotherapy and thoracic RT and the application of prophylactic cranial irradiation for complete responders need to be investigated in the future.

Age Factors↗
PubMed2002

Hydroa-like cutaneous T-cell lymphoma: a clinicopathologic and molecular genetic study of 16 pediatric cases from Peru.

Hydroa-like cutaneous T-cell lymphoma (hydroa-like CTCL) is an unusual pediatric malignancy with a poor prognosis. An impressive cutaneous rash characterized by edema, blisters, ulcers, crusts, and scars, resembling hidroa vacciniforme, is seen mainly on the face and sometimes on the extremities. The lesion consists of lymphomatous T-cell infiltration of the skin and subcutis with variable exocytosis and angiocentricity. It has been also called edematous, scarring vasculitic panniculitis and hydroa-like lymphoma. An association with Epstein-Barr virus has been suggested. The differential diagnosis includes other cutaneous lymphomas, particularly the cutaneous nasal type T/natural killer-cell lymphoma, mycosis fungoides, precursor T-cell lymphoblastic lymphoma, nonspecific peripheral T-cell lymphoma, cutaneous anaplastic large cell lymphoma, and subcutaneous panniculitic T-cell lymphoma. Other differential diagnoses are inflammatory dermatopathies and panniculitides. Based on a series of 16 such cases referred to the Institute of Neoplastic Diseases, the objective of this report is not only to provide a better clinicopathologic understanding of this entity but also a reappraisal of it as a malignancy. The male/female frequency ratio was 1:1. The median age was 10 years old. All cases showed predominant facial involvement with edema, blisters, ulcers, crusts, and scars. Chemotherapy and/or radiotherapy had little or no benefit. The prognosis was usually dismal. The lymphoma extended from the epidermis to the subcutis, with frequent angiocentric and periadnexal array. Lymphoma cells were mostly of intermediate size with dense hyperchromatic nuclei, inconspicuous nucleoli, and infrequent mitosis. A scanty and variable inflammatory background was found. The lymphoma cells displayed T-cell cytotoxic phenotype. In addition, they were negative for the natural killer cell antigens CD56 and CD57. Epstein-Barr virus in situ hybridization was positive in the six cases in which it was assayed. T-cell receptor gamma (TCRgamma) displayed monoclonal-type rearrangement in four cases studied. Our findings indicate that hydroa-like CTCL is an independent clinicopathologic entity that affects children. Consequently, it should be considered an independent subset of CTCLs and be included as such in the classification of neoplastic diseases of the lymphoid tissues.

Adolescent↗
PubMed1999

Anatomical study of vestibulospinal neurons in lampreys.

The present study was carried out to characterize anatomically the vestibulospinal (VS) system of lampreys. Cobalt-lysine or Texas Red dextran amines were applied in vitro to the rostral spinal cord. Two distinct populations of VS neurons were labeled in the ventral nucleus of the area octavolateralis. The rostral group, comprising the intermediate octavomotor nucleus (ION), contained between 100 and 150 neurons, having somata of variable size and morphology. Intracellular injections of Lucifer Yellow in single neurons revealed ION VS neurons with dendrites extending in the ventrolateral alar plate as well as medially in the basal plate. The caudal group, comprising the posterior octavomotor nucleus (PON), contained approximately 65 neurons, most of which were unipolar with round or oval somata. To study the projections of VS axons, cobalt-lysine was injected into the ION or PON regions in the brainstem. Axons from the ION projected to the ipsilateral spinal cord, whereas PON axons decussated within the basal plate giving out descending and ascending branches. The descending branch projected to the contralateral spinal cord. Injections of two fluorescent dextran-amines, each restricted to one side of the spinal cord, did not double-label VS cells in either octavomotor nuclei, indicating that the projections of each nucleus are restricted to one side. Injections of horseradish peroxidase further caudally in the spinal cord revealed that VS axons from the ION reached past the gill region. Our results indicate that the organization of the VS system of lampreys is similar to that observed in other vertebrates.

Animals↗
PubMed2002

Fluxional processes in diamagnetic and paramagnetic allyl dicarbonyl and 2-methylallyl dicarbonyl molybdenum histidinato complexes as revealed by spectroscopic data and density functional calculations.

This work describes a detailed study on the structure and dynamics of pseudooctahedral low-valent complexes of the type [Mo(His-N(epsilon)-R)(eta-2-R'-allyl)(CO)(2)] (His=N(delta),N,O-L-histidinate; R=H, R'=H (1); R=C(2)H(4)CO(2)Me, R'=H (2); R=H, R'=Me (3); R=C(2)H(4)CO(2)Me, R'=Me (4)). These diamagnetic 18-electron complexes were comprehensively characterized spectroscopically and by X-ray crystallography. In the solid state, the (substituted) allyl ligand is in an endo position in all compounds, but it is trans to the His-N(delta) atom in 1 and 2, whereas it is trans to the carboxylate O atom for the 2-Me-allyl compounds 3 and 4. In solution, both isomers are present in a solvent-dependent equilibrium. The third isomer (allyl trans to His-NH(2)) is not spectroscopically observed in solution. This is in agreement with the results from density functional (DFT) computations (BPW 91 functional) for 1 and 3, which predict a considerably higher energy (+6.3 and +5.9 kJ mol(-1), respectively) for this isomer. A likely path for isomerization is calculated, which is consistent with the activation energy determined by variable temperature NMR measurements. At least for 3, the preferred path involves several intermediates and a rotation of the 2-Me-allyl ligand. For the paramagnetic 17-electron congeners, DFT predicts the exo isomer of 3(+) with the 2-Me-allyl ligand trans to the carboxylate O atom to be by far the most stable isomer. For 1(+), an endo-exo equilibrium between the isomers with the allyl ligand trans to the carboxylate O atom is suggested. These suggestions are confirmed by EPR spectroscopy on the electrochemically generated species, which show signals for one- (4) and two- (2) metal-containing compounds. The appearance of the EPR spectra may be rationalized by inspection of the SOMOs from DFT calculations of the species in question. The notion of a metal-centered oxidation is also substantiated by IR spectroelectrochemistry and by UV/Vis spectra of the 17-electron complexes. Upon depleting the metal of electron density, the stretching vibrations of the carbonyl ligands shift more than 100 cm(-1) to higher wavenumbers, and the carbonyl vibration of the metal-coordinated carboxylate shifts by about 50 cm(-1). A color change from yellow to green upon oxidation is observed visually and quantified by the appearance of a new band at 622 nm (2(+)) and 546 nm (4(+)), respectively.

Crystallography, X-Ray↗
PubMed1980

Early development of the brain and spinal cord in dysraphic mice: a transmission electron microscopic study.

The hindbrain and spinal cord were studied by transmission electron microscopy with and without lanthanum nitrate treatment in nine-day embryos of the loop-tail (Lp) mutant mouse. Homozygous (Lp/Lp) individuals exhibit dysraphism from the hindbrain caudally throughout the embryo; in +/+ and Lp/+ individuals, the brains and spinal cords are normal. In contrast, the ventricular cells in the abnormal hindbrain and spinal cord showed increased amounts of intercellular space in an area intermediate between the luminal border and basal zone, and a flattening which occurs variably in their luminal surfaces. A most striking difference occurred in the frequency of gap junctional vesicles, circular structures bounded by a double membrane and containing ribosome-like material. A quantitative analysis of the distribution of these organelles revealed that they are more numerous in the dysraphic hindbrain and lumbosacral spinal cord of the abnormal animals than in comparable regions of the normal; however, in the cervicothoracic spinal cord, the frequency of these vesicles is similar. In specimens treated with lanthanum, the tracer freely penetrated the luminal junctional complexes in both normal and abnormal animals, but was not present between the membranes of the gap junctional vesicles. The developmental significance of gap junctional vesicles frequently located in juxtaluminal regions of mitotic cells, but also found deeply in dividing cells, is not known; they may relate to cell-to-cell attachment and/or communication. In any event, further study of them may prove valuable in understanding normal and abnormal development of the neural tube.

Animals↗
PubMed1986

Motor endplate position of rat gastrocnemius muscle.

In this study, the relative endplate position of fibers of rat gastrocnemius caput mediale (GM) muscle was determined by counting numbers of sarcomeres. Isolated fibers were teased from the proximal, intermediate, and distal regions of the muscle. Endplates of distal fibers were located on the proximal third of their lengths. Endplates of intermediate fibers were located at half fiber length, and for proximal fibers, a variable endplate position was obtained: in half of the muscles studied, endplates occurred around the proximal one-third and in the other half near the midpoint of the fiber. Endplate position relative to fiber length was thus found to be dependent on the region of the muscle. Changes in the orientation of endplate zone relative to the muscle belly is likely to take place with changes in muscle length, as shown by a planimetric muscle model. It is argued that architecture of pennate muscles may highly affect characteristics of motor unit potentials.

Animals↗
PubMed1993

Environmental effects on fitness-sets shape and evolutionarily stable strategies.

Most models on the evolution of sex allocation and life-history traits are based on the existence of compensations between these traits, and often consider them as linear. With a simple model of physiological response to richness of the environment, we show that not only can these compensations take many different shapes, but also that this shape varies as a function of the resource level. Consequently, evolutionarily stable strategies (ESSs) calculation can give different results for the same two functions according to resource level. Thus, selection can act in different directions depending on the "quality" of the environment. Moreover, genetic variability in the resource allocation strategies is likely to be shown better in intermediate environments, where the proportions of allocation have the most crucial effect on the phenotype.

Animals↗
PubMed1995

Vitamin D receptor gene polymorphism, bone mass, body size, and vitamin D receptor density.

We determined vitamin D receptor (VDR) gene alleles (based on the BsmI restriction site polymorphism), duodenal mucosal receptor density, bone mass at spine and total body, and body size in 32 healthy premenopausal females. While we found no relationship between allele and receptor density in duodenal mucosa, bone mineral content (BMC) at both spine and total body was significantly associated with VDR gene alleles. BMC was highest for the bb allele, lowest for BB, and intermediate for Bb. A similar association was noted between allele and body size variables, particularly weight. When BMC was adjusted for body weight, the association with VDR polymorphism disappeared. The VDR gene polymorphism may be affecting bone mass not through classical nutritional mechanisms (e.g., intestinal calcium absorption), but through an influence on body size.

Adult↗
PubMed1984

Astrocyte cell lineage. III. The morphology of differentiating mouse astrocytes in colony culture.

Disaggregated cells of newborn DBA/1J mouse neopallium were grown in colony cultures, and colonies of cells at various stages of differentiation along the astrocyte cell lineage were examined after 3 days, 1, 2 and 4 weeks by electron microscopy and by NBD-phallacidin which demonstrates the distribution of microfilaments. The earliest astrocyte precursor cells or glioblasts are closely apposed epithelial cells that rarely have junctions. Their scanty cytoplasm contains many free ribosomes but few microfilaments. The cells in the next stages of astrocyte lineage or proastroblasts are flat and are separated from each other to a variable degree. They have intercellular junctions associated with microfilaments and contain singly dispersed intermediate filaments. The proastroblasts gradually differentiate into astroblasts which have a similar morphology except that in addition to the singly distributed intermediate filaments they also contain intermediate filaments arranged into bundles of various sizes. The mature fibrous astrocytes have well-defined processes and distinct perikarya. They form from astroblasts in culture and also contain numerous bundles of intermediate filaments. The dibutyryl-cyclic AMP (dBcAMP)-induced astrocytes in culture in contrast are large stellate cells similar to reactive astrocytes found around sites of injury in the brain. On the basis of these and previous immunocytochemical studies of the formation and distribution of intermediate filaments in the cytoplasm of differentiating astrocytes, criteria are proposed for identification of different cells along the astrocyte lineage.

Animals↗
PubMed2004

Matching total body oxygen consumption and delivery: a crucial objective?

The strength of the rationale for incorporating total body oxygen consumption (VO(2)) and delivery (DO(2)) into our decision making strategies contrasts with the absence of demonstrated benefits of bedside calculations in clinical practice. This situation mandates a careful reappraisal of the theoretical limitations of bedside calculations of DO(2) and VO(2), including a re-evaluation of the clinical situations in which these calculations are valid. Three levels of complexity can be distinguished when analysing a patient's hemodynamic status: 1) simple cases where investigations can be limited to clinical monitoring, including lactate changes over time; 2) intermediate situations requiring invasive investigations in which continuous monitoring of VO(2)-related variables such as cardiac output and mixed venous oxygen saturation often provide enough information to guide clinical decision; and 3) complex situations where assessment of VO(2) and VO(2)/DO(2) analysis might be recommended. Although studies that support such recommendations are limited they are based on a widely accepted physiological model. VO(2) and DO(2) analysis is also limited by theoretical and technical difficulties. In this article, we discuss the validity of these limitations in the bedside assessment of VO(2) and DO(2), and review data supporting the use of VO(2)/DO(2) analysis in the clinical evaluation of complex cases.

Cardiac Output↗
PubMed1993

How do physiological components of balance affect mobility in elderly men?

The purpose of this study was to assess the relationship between physiological components of balance and mobility in elderly men without significant disease. Our a priori hypothesis was that physical function is influenced more by accumulated modest impairments than by a single deficit. We examined 39 ambulatory men (> 69 years). Subjects were classified functionally as high, intermediate, or low. Assessment included mobility functions (6-minute walk, mobility skills, reach, 10ft walk time) and physiological components of balance: sensory (vibration, proprioception, vision, vestibular), effector (ankle, knee, hip strength, range of motion), and central processing (response time to perturbations). All mobility functions were significantly (p < .05) different between groups. Impairments in components of postural control were rarely different between groups: the major differences were in ankle strength and visual fields. The number of impaired domains differed across the three groups. Nineteen percent of the low group had at least three domains impaired; none of the intermediate or high groups were impaired in three domains. Fifty-six percent of the low, 20% of the intermediate, and 7% of the high were impaired in two or more domains. Variability in specific mobility measures was also predicted by the number of impaired domains. The decline in physical function may be better explained by the accumulation of deficits across multiple domains than by any single specific impairment.

Accidental Falls↗
PubMed1984

Axon strata of the cerebral wall in embryonic mice.

The stratification of principal fiber systems affiliated with the developing neocortex has been analyzed by means of HRP tracing methods, monoamine histofluorescence and silver impregnations in mouse embryos ranging from the 15th to 16th embryonic day (E15/16) to the end of gestation (E19 = the day of birth). As early as E15/16 a fiber stratum divides the subplate and marks the inferior boundary of the developing cortex. Axons coursing in this fiber plane, termed the external sagittal stratum (ESS), include components of at least 5 identifiable systems: thalamocortical, corticothalamic, ipsilateral corticocortical, callosal and monoaminergic. The neocortical afferents of extrinsic origin, i.e., the thalamocortical, callosal and monoaminergic systems, cross the intermediate zone from their separate directions and converge upon the ESS. After a variable course through this stratum, single fibers ascend from their parent fascicles to ramify densely in the cortical subplate (CSB). Fibers of each of the extrinsic afferent systems mingle with each other and with locally arising axons within the CSB. Axons of the monoaminergic projection as well as fibers of the thalamic projection cross the cortical plate to ramify in the marginal zone. Other axons apparently of local intracortical origin course tangentially through the cortical plate. Otherwise, the cortical plate is devoid of proliferating axons at this early developmental stage. The set of observations illustrates the existence of sharply defined boundaries between axon-rich and axon-poor strata of the developing neocortex. These boundaries also compartmentalize postmigratory neurons with respect to their state of differentiation.

Animals↗
PubMed1995

In situ gene expression of growth hormone (GH) receptor and GH binding protein in adult male rat tissues.

Pituitary growth hormone (GH) acts as a growth promoter in a wide range of tissues after binding to its specific GH receptor (GHR) or to a cytosolic circulating GH binding protein (GHBP). To further characterize GH target cells in the rat, in situ hybridization was used to investigate the tissue and cell distribution of mRNAs encoding GHR and GHBP, and their hepatic developmental expression was examined. Cryostat sections of adult male rat tissue were hybridized with [35S]dATP-labeled oligonucleotide antisense probes, one directed against a specific sequence of the intracellular domain of rat GHR mRNA, the other against the hydrophilic tail of rat GHBP mRNA. Several tests were carried out to validate the in situ detection of mRNA. Co-expression of the two transcripts in liver, spleen, thymus, kidney, adrenal, skin, muscle, heart, and pituitary was autoradiographically detected. However, relative expression levels, as demonstrated by computer-assisted microdensitometry, appeared to be variable. Both transcripts showed higher levels of expression in the liver, anterior and intermediate pituitary lobes, outer kidney medulla, adrenal cortex, skin epidermis, heart and muscle, but lower levels in spleen, thymus, hypodermis, adrenal medulla and posterior pituitary lobe. As a physiological control, hepatic levels of expression were examined during development, and the two forms of mRNA were found to be present at low levels in fetal liver, increasing considerably after birth. These results permit the identification in the adult male rat of cells that might be directly responsive to GH, and demonstrate the differential expression of rGHR and rGHBP transcripts.

Adrenal Glands↗
PubMedDate not supplied

Ethanol reinforcement and its relationship to saccharin preference in Wistar rats.

Forty rats were given a choice between 0.1% sodium saccharin and water. Based on their intakes, three groups of six rats representing high, intermediate, and low saccharin preferences were selected. These rats were reduced to 80% of their free-feeding weights. Ethanol was established as a reinforcer by use of a food-induced drinking procedure. Between-group differences were assessed based on response rates across acquisition sessions (0, 1, 2, 4, 5.7, 8%, w/v), a fixed-ratio series (1, 2, 4, 8, 1), and a concentration series (8, 5.7, 4, 2, 2, 4, 5.7, 8, 11.3, 16, 22.6, 32, 8%, w/v). In 29 of 32 conditions which were analyzed, the mean number of responses for ethanol was higher for the high saccharin preference group than for the low, and in 25 of 32 conditions, the intermediate group fell between the high and the low. However, there was considerable variability within groups across all conditions, such that mean between-group differences were not significant. This variability may be reduced by considering diet preferences in addition to saccharin preference. Nonetheless, these results offer limited support for the increasing body of evidence indicating a relationship between the factors mediating ethanol self-administration and those involving ingestion of palatable foods and fluids.

Animals↗
PubMed1999

Whole blood serotonin and plasma beta-endorphin in autistic probands and their first-degree relatives.

BACKGROUND: Whole blood serotonin (5-HT) and C-terminally directed beta-endorphin protein immunoreactivity (C-ter-beta-EP-ir) are known to be elevated in autistic subjects and might be possible markers of genetic liability to autism. This study thus investigates the familial aggregation of 5-HT and of C-ter-beta-EP-ir levels in first degree relatives of autistic probands. METHODS: In a sample of 62 autistic subjects and 122 of their first-degree relatives, compared to age and sex-matched controls, we measured 5-HT by radioenzymology and C-ter-beta-EP-ir by radioimmunoassay. RESULTS: We confirm the previously reported familiality of hyperserotoninemia in autism as mothers (51%), fathers (45%) and siblings (87%) have elevated levels of 5-HT, and we reveal presence of elevated levels of C-ter-beta-EP-ir in mothers (53%) of autistic subjects. CONCLUSIONS: Familial aggregation of quantitative variables, such as concentration of neurotransmitters, within unaffected relative could serve as an intermediate phenotype and might thus help the search of genetic susceptibility factors in autism.

Adolescent↗
PubMed2002

Histology of the bone-tendon interfaces of limb muscles in lizards.

Lizards exhibit continual bone growth at the epiphysis, and their limb muscles are distributed differently from those of mammals because of differences in weight bearing. We therefore characterized the bone-tendon (B-T) interface (also termed the enthesis) in lizards. Using the forelimbs of five monitor lizards and three iguanas, we performed histological investigations on 57 B-T interfaces. Most reptilian tendons were very short and were often composed of wavy fiber bundles. Fibrocartilage (FC)-mediated direct insertion was observed at all epiphyses, whereas periosteum-mediated indirect insertions, including fleshy attachments, were often located on the flat surfaces of the pectoral girdles and at the diaphyses of the limb bones. The reptilian B-T interface was characterized by variability in the morphology of the FC-mediated insertions, especially by morphologies intermediate between those of FC- and periosteum-mediated interfaces; i.e., 1) various degrees of absence of the clear FC zonation seen in mammals, including the tidemark; 2) involvement of the periosteum in the FC; 3) the presence of various types of FC cells in the tendon near the interface, to reinforce the tendon against compression or shear stress; and 4) both FC and hyaline cartilage (lateral articular cartilage) receiving the tendon at the epiphysis. Overall, variations in the connective tissue, especially the FC tissue, were very evident in the reptilian B-T interface. The specific structures of the interfaces probably represent adaptations to the continuous growth and loose joint structures of lizards.

Animals↗
PubMed1991

Relation of giant cell arteritis to polymyalgia rheumatica.

Polymyalgia rheumatica and temporal arteritis appear to be separate syndromes rather than two manifestations of an underlying giant cell arteritis. Polymyalgia rheumatica is a synovitis that may be persistent or recurrent, while temporal arteritis is almost always a single episode; documented recurrences are rare. The two syndromes frequently occur in the same patient although not necessarily at the same time and they may be separated by a long interval. In some patients with polymyalgia rheumatica, giant cell arteritis is found on biopsy of an asymptomatic temporal artery. The frequency of this concurrence is variable in different populations. It is high in Scandinavia, low in Israel and intermediate between these extremes in other populations that have been studied.

Giant Cell Arteritis↗
PubMed2001

Fibroid calcification after uterine artery embolization: ultrasonographic appearance and pathology.

PURPOSE: To describe the ultrasonographic (US) appearance of fibroid calcification occurring after uterine artery embolization (UAE) and discuss its etiology and pathology. MATERIALS AND METHODS: Twenty-seven of a total of 38 patients were followed up clinically and with duplex US for longer than 6 months after UAE for uterine fibroids. At US, changes in uterine size, fibroid vascularity, and morphology have been recorded. Pathologic studies were performed by one of the authors on resected specimens from a different cohort of patients, at intervals ranging from 4 months to 1 year after UAE. RESULTS: Twenty patients reported complete resolution of symptoms. In 16 of these, a reduction in fibroid volume of 70%-85% was recorded and, at US, the development of a peripheral hyperechoic rim around an increasingly hypoechoic fibroid was noted. Computed tomography in two patients revealed it to be a rim of calcium. Histologic studies in a different cohort of patients who had undergone hysterectomy at variable intervals after UAE demonstrated early aggregation of polyvinyl alcohol (PVA) particles, an intermediate giant cell inflammatory reaction, and calcification in the periphery of the infarcted fibroid at 6-12 months. CONCLUSION: Calcification is the end stage of hyaline degeneration. However, its peripheral location is unlike that of natural fibroid involution and hyaline necrosis. Pathologic studies in resected human fibroids after embolization suggest that its development is the end result of aggregation of PVA particles in peripheral fibroid arteries.

Adult↗