Degranulating cytotoxic lymphocytes inflict multiple damage pathways on target cells.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
M S Williams
Publications and source records attributed to M S Williams.
Cystic neuroblastoma of infancy.
Cystic neuroblastoma is exceedingly rare; only 29 cases have been reported in the medical literature. The authors treated two children with cystic neuroblastoma. The first was a 2-week-old boy with an adrenal lesion; the second was a 15-month-old girl with solitary thoracic cystic neuroblastoma. Cystic neuroblastoma is located, almost exclusively, in the adrenal gland. In contrast to solid neuroblastoma, cystic neuroblastoma has a benign course. Cystic neuroblastoma is diagnosed earlier than solid neuroblastoma, and the former rarely presents with metastatic lesions. All previous reported cases of cystic neuroblastoma were diagnosed before 21 months of age. The presence of calcification was rare, and only 9.5% had documented elevation of the vanillylmandelic acid or homovanillic acid level. Surgical resection of all gross tumor was accomplished in 86% of children with cystic neuroblastoma, and in this group none of the patients had reported recurrent disease. Both present cases also had surgical resection of the entire gross tumor, and likewise have had no evidence of recurrent disease. This report brings the total number of reported pediatric cases of cystic neuroblastoma to 31; to the authors' knowledge, this is the first report of a child with solitary cystic neuroblastoma in an intrathoracic location.
Adrenal Gland Neoplasms↗
Patterson-Lowry rhizomelic dysplasia: a possible second example.
We present a possible example of Patterson-Lowry rhizomelic dysplasia. If so, this is only the second reported individual with this disorder and the first instance of its recognition in a child. Clinical features in this child are compared with the other described individual and differential diagnosis is discussed. Primary features include rhizomelic foreshortening most markedly affecting the arms, limitation of shoulder abduction, mild generalized foreshortening of the long bones, mild short stature, coxa vara, and specific radiological features.
Body Height↗
Apoptotic cell death induced by intracellular proteolysis.
To mimic the injection of granzymes into target cells by cytotoxic lymphocytes or the activation of endogenous proteases in programmed cell death, the proteases chymotrypsin, proteinase K, or trypsin were loaded into the cytoplasm of several different cell types using the osmotic lysis of pinosomes technique. Internalization of these proteases caused cell lysis within several hours, accompanied by extensive nuclear damage in most but not all combinations of target cells and proteases. This nuclear damage, quantitated by DNA release from nuclei, was associated with apoptotic features including DNA fragmentation into nucleosomal ladders, chromatin condensation, nuclear fragmentation, and membrane blebbing. Agents reported to block programmed cell death, including aurintricarboxylic acid, inhibitors of energy metabolism, and protein or RNA synthesis, failed to block this protease-induced death, although some inhibited nuclear damage. In separate experiments, introduction of staphylococcal nuclease into cells led to near complete (at least 75% of total) nucleosomal DNA fragmentation within 6 to 8 h. Condensation of chromatin did not accompany this fragmentation to the same extent, and there was approximately a 10-h lag between half-maximal DNA fragmentation and 50% loss of membrane integrity. The results suggest that activation of intracellular proteases during cell death by any molecular pathway could give rise to apoptotic morphology and DNA fragmentation.
Apoptosis↗
Effect of 3'-amino-2',3'-dideoxycytidine on DNA replicative intermediates.
3'-Amino-2',3'-dideoxycytidine (3'-NH2-ddCyd) is a 3'-modified deoxycytidine analog that specifically inhibits DNA synthesis. Inhibition of chain elongation at the replication fork was examined utilizing a batch hydroxylapatite chromatography method. Exponentially growing cells were exposed to 3'-NH2-ddCyd and the diterpene aphidicolin for 9.5 hr at concentrations that inhibited DNA synthesis by approximately 60 and 90%, as determined by precursor uptake. Both agents demonstrated a concentration-dependent inhibition of pulse labeling of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) generated by a limited alkaline lysis procedure. Upon removal of drug, the rate of elongation of pulse-labeled DNA was similar to that of untreated cells at both concentrations of aphidicolin and at the low concentration of the amino analog. Under these conditions, no reduction in cell survival was observed using the clonogenic assay technique. However, at the high concentration of 3'-NH2-ddCyd, the rate of elongation following drug removal was one-third that of untreated cultures, and a 50% loss in cell viability was observed. Furthermore, upon incubation of purified dsDNA with the Klenow fragment of Escherichia coli DNA polymerase I or purified ssDNA with calf thymus terminal deoxynucleotidyl transferase, only DNA from cells treated with the high concentration of 3'-NH2-ddCyd served as a poor template for further synthesis. The results indicate that 3'-NH2-ddCyd, in a concentration-dependent manner, inhibits DNA synthesis by reducing the rate of chain elongation at the replication fork, which subsequently leads to a functional blocking of 3'-ends in DNA. The data suggest that there may be a relationship between loss of cell viability and reduction in the number of 3'-ends available for DNA replication.
Animals↗
Investigation of thermoregulatory characteristics in patients with Prader-Willi syndrome.
A survey instrument is used to assess temperature regulation characteristics in children with Prader-Willi syndrome (PWS) compared to 3 control groups: sibs of PWS patients (SIB), neurodevelopmentally handicapped children (ND), and age and gender matched well children (WC). Significant differences were found between PWS patients, SIB controls, and WC controls in the prevalence of febrile convulsions, fever-associated symptoms, and temperature less than 94 degrees F. No differences were noted in any variable between the PWS patients and the ND controls, suggesting that these abnormalities are not unique to PWS, but can occur in any neurodevelopmentally handicapped individual, further suggesting these do not necessarily reflect syndrome-specific hypothalamic abnormalities.
Body Temperature Regulation↗
Effect of epidural analgesia for labor on the cesarean delivery rate.
OBJECTIVE: To use meta-analysis to evaluate the effect of epidural analgesia on the cesarean delivery rate. DATA SOURCES: The MEDLINE data base was searched for articles published in English between January 1981 and April 1992. We also interviewed experts and conducted a bibliographic follow-up and manual review of recent journals published from April to July 1992. METHODS OF STUDY SELECTION: We excluded articles with irrelevant titles, and those case studies, book chapters, or articles that did not provide primary and relevant data. Two hundred thirty articles were read, including articles that reported on women of standard obstetric risk and on cesarean delivery rates for an epidural group and for a concurrent no-epidural group. These criteria yielded six studies for a primary analysis and two others for a secondary analysis. DATA EXTRACTION AND SYNTHESIS: The sample size of the epidural and no-epidural groups and the number of cesareans within each group were extracted. Tests of homogeneity were conducted. The pooled cesarean delivery risk difference as a result of epidural analgesia was estimated. The cesarean rate for women undergoing epidural analgesia was ten percentage points greater than for no-epidural women (P < .05). More than a nine percentage point increase was shown for cesarean deliveries for dystocia (P < .05), when pooling either all studies or only randomized studies. CONCLUSIONS: The results of this meta-analysis strongly support an increase in cesarean delivery associated with epidural analgesia. Further research should evaluate the balance between analgesia associated with the use of epidurals, and postpartum morbidity and costs associated with cesarean deliveries.
Analgesia, Epidural↗
Single-radial-immunodiffusion as an in vitro potency assay for human inactivated viral vaccines.
Single-radial-immunodiffusion (SRID) assays have been used to determine the potency of all human inactivated influenza virus vaccines licensed by the Food and Drug Administration for use in the United States since 1978. SRID replaced less reliable tests which were based on the aggregation of erythrocytes by the hemagglutinins of influenza viruses. Similar SRID assays have been used experimentally to determine the potency of inactivated polio and rabies vaccines. In each case, the assays are based on the diffusion of viral antigen into an agarose gel containing specific antibodies to the antigen being measured. For influenza and rabies, disruption of the virions with a detergent is necessary to permit the diffusion of the appropriate antigens, where as with polio, intact virions are allowed to diffuse. The interaction between antigen and antibody produces a zone of precipitation whose size is directly proportional to the amount of antigen applied. A potency value for unknowns is obtained by comparing the sizes of zones produced by unknown preparations to the sizes of zones obtained with a calibrated reference of known antigen content. Once the specific reference antigens and antibodies are prepared and the test standardized, it is a remarkably simple technique which unlike agglutination assays is very reproducible, relatively unaffected by minor variations in test conditions and is far less time consuming and cumbersome than in vivo assays for potency such as those done by inoculating mice or monkeys. More importantly, clinical studies demonstrate that standardization of influenza vaccines by SRID provides a better correlate of human immunogenicity than previous methods.
Drug Evaluation, Preclinical↗
Patterns of contraceptive use and pregnancy among young Hispanic women on the Texas-Mexico border.
Our objective was to identify significant family planning and health access problems of young Hispanic women on the Texas-Mexico border. Samples of 300 young Hispanic women living in each of the twin cities of El Paso and Juarez were interviewed regarding their knowledge, attitudes, and experiences with respect to birth control, pregnancy, maternal and child health, and health-care services. Knowledge and attitudes of the women about birth control technology were assessed along with their beliefs regarding the use of such technology. Results showed that contraceptive knowledge and usage patterns for young Hispanic women in Juarez and El Paso were significantly different. They relied on different types of birth control methods and also differed with respect to confidence in these methods and related medical services. Both groups reflected positive attitudes toward both child bearing and use of birth control although Juarez women were significantly more favorable toward child bearing. Both groups overwhelmingly favored female doctors. The young women studied have accepted the need for birth control, prefer fewer children, and have some degree of confidence in medical services. Their knowledge and use of reliable versus unreliable birth control devices appear to be major areas requiring culturally sensitive intervention.
Acculturation↗
Marden-Walker syndrome: a case report and a critical review of the literature.
We present a patient with blepharophimosis, joint contractures, immobile facies, decreased muscular bulk, postnatal growth retardation, developmental delay, micrognathia, cleft palate, camptodactyly, arachnodactyly, pectus, kyphoscoliosis, hypospadias, and absent deep tendon reflexes. These findings are consistent with Marden-Walker syndrome (MWS). Twenty-two additional cases in the literature are reviewed. Diagnostic criteria are proposed, and the spectrum of variability is discussed. Evidence for autosomal recessive inheritance is reviewed as is the differential diagnosis. Possible pathogenetic mechanisms are considered.
Abnormalities, Multiple↗
The anatomy of dopamine in monkey and human prefrontal cortex.
This chapter reviews recent evidence establishing the comparable organization of dopamine afferents and dopaminergic receptors in the human and monkey prefrontal cortex. Light microscopy using a dopamine-specific antibody reveals that the dopamine innervation in the human prefrontal cortex exhibits a distinct bilaminar distribution with dense bands of fibers in the upper and deeper strata of the cortex, closely resembling the patterning of dopamine fibers in the monkey prefrontal cortex. Also, EM-immunohistochemistry has now revealed identical synaptic complexes both in human and monkey. In both species, dopamine axons from symmetric synapses predominantly on the spines of pyramidal cells. In many cases, the same spine is apposed by an asymmetric, putatively excitatory synapse. Finally, both in human and monkey prefrontal cortex, the dopamine D1-specific ligand, 3H-SCH23390, and the D2-specific ligand, H3-raclopride, label binding sites in laminar positions which match the location of the densest dopamine innervation. These results indicate that the organization of the cortical dopamine system is essentially the same in macaque monkey and human and that the nonhuman primate is a suitable animal model for analysis of dopamine function in prefrontal cortex.
Afferent Pathways↗
Cross-reactive antibodies induced by a monovalent influenza B virus vaccine.
Influenza viruses related to the markedly antigenically divergent strains B/Yamagata/16/88 and B/Victoria/2/87 are circulating in human populations. Adults develop cross-reacting antibodies against recent and earlier influenza B virus strains after vaccination with B/Yamagata/16/88, probably because of previous influenza B virus infections or immunizations. Vaccines containing B/Yamagata/16/88 should adequately protect adults against B/Victoria/2/87 infections.
Adult↗
Antibody responses to influenza B viruses in immunologically unprimed children.
The cocirculation in several parts of the world of influenza viruses B/Yamagata/16/88 and B/Victoria/2/87, which are genetically and antigenically divergent, has prompted the question of whether immunization with one viral antigen is sufficient for protection against both strains. Twenty-three high-risk infants and young children were immunized with a commercial trivalent influenza vaccine containing the antigens of influenza virus B/Yamagata/16/88. When antibodies against influenza viruses B/Yamagata/16/88 and B/Victoria/2/87 were determined, increases developed uniformly to both in the sera of primed children previously exposed to influenza virus B/Victoria/2/87 by immunization or infection. Antibodies against B/Yamagata/16/88 developed in the sera of unprimed children with titers similar to those of the primed children. However, antibodies to B/Victoria/2/87 were not detected in the sera of the unprimed children. These data suggest that children without appropriate immunologic priming may not be protected against an infection with a B/Victoria/2/87 strain after vaccination with a B/Yamagata/16/88 strain. Immunization with more than one influenza B virus strain may be desirable in some high-risk pediatric patients if divergent influenza B viruses circulate.
Antibodies, Viral↗
Specific inhibition of DNA biosynthesis induced by 3'-amino-2',3'-dideoxycytidine.
3'-Amino-2',3'-dideoxycytidine (3'-NH2-dCyd) produced an S-phase-specific block in exponentially growing L1210 leukemia cells. The monophosphate and triphosphate forms of the drug were detected within a few hours of 3'-NH2-dCyd treatment of intact cells. No significant change in the deoxynucleoside triphosphate levels was observed during the early stages of treatment. However, by 24 h a 2-fold increase in the amount of the deoxynucleoside triphosphates was seen. The triphosphate form of the drug competitively inhibited dCTP incorporation into calf thymus DNA using highly purified DNA polymerase alpha. The Ki was determined to be 9.6 microM with respect to dCTP. Incorporation of the analogue into DNA was not detected. On the other hand, sucrose gradient analysis suggested that incorporation of the analogue into actively synthesized DNA may account for the biological activity of this compound. Treatment with 3'-NH2-dCyd induced single-strand breaks in actively synthesized DNA, but no double-strand breaks were observed in the presence of the analogue. The data indicate that 3'-amino-2',3'-dideoxycytidine specifically interferes with DNA replication at the level of DNA polymerase by inhibiting chain elongation.
Animals↗
Phenotypic variation in the del(12p) syndrome.
Previous reports suggested the existence of a del(12p) syndrome. Phenotypic abnormalities associated with del(12p) appear to be mental retardation, microcephaly, and micrognathia. The patient with del(12p) reported here was normocephalic and large for gestational age. She probably had sclerocornea, a finding not previously associated with del(12p). Phenotypic variation in del(12p) syndrome is probably caused by differences in the size of the deleted segment and/or the presence or absence of mutant genes on the homologous 12p segment.
Abnormalities, Multiple↗
Experimental infection of ectoparasitic arthropods with Rickettsia prowazekii (GvF-16 strain) and transmission to flying squirrels.
Epizootiologic studies conducted during the past few years showed the existence of widespread natural infection of the southern flying squirrel, Glaucomys volans, with epidemic typhus rickettsiae, Rickettsia prowazekii. The ecological findings strongly implicated transmission of the etiologic agent by an arthropod vector. Studies were conducted under controlled laboratory conditions to determine whether ectoparasites naturally associated with flying squirrels (squirrel fleas, lice, mites and ticks) were capable of acquiring, maintaining and transmitting the infection. Also studied were the cat flea, oriental rat flea and the human body louse. Flying squirrels inoculated with the GvF-16 strain of R. prowazekii circulated rickettsiae in their blood for 2-3 weeks, thus providing ample opportunity for arthropods feeding on them to become infected. The results with Dermacentor variabilis ticks indicated that the rickettsiae did not consistently survive in this insect and were not passed to the eggs of adult females that had been infected subcuticularly. Mites became infected by feeding on infectious blood but failed to sustain the infection. Also, mites fed on an infected flying squirrel did not transmit the infection to a normal squirrel. Squirrel, cat, and oriental rat fleas readily became infected by feeding on a rickettsemic host or on infectious blood through membranes, but failed to transmit the infection to susceptible flying squirrels. In the studies with flying squirrel lice, however, transmission of epidemic typhus from infected to uninfected flying squirrels was demonstrated. Infection of the human body louse with the GvF-16 flying squirrel strain of R. prowazekii was similar to that previously observed with classical human strains, viz., multiplication of the rickettsiae and excretion in the feces.
Animals↗
New developments in the measurement of the hemagglutinin content of influenza virus vaccines by single-radial-immunodiffusion.
Explore the source record for details and available documents.
Detergents↗
Comparative antigenicity and immunogenicity of 1976 influenza virus vaccines: results of mouse protection experiments.
Explore the source record for details and available documents.
Animals↗