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At least 361 records · Page 20Linked to original sources

Pressure-regulated volume control ventilation vs synchronized intermittent mandatory ventilation for very low-birth-weight infants: a randomized controlled trial.

OBJECTIVE: To test the hypothesis that pressure-regulated volume control (PRVC), an assist/control mode of ventilation, would increase the proportion of very low-birth-weight infants who were alive and extubated at 14 days of age as compared with synchronized intermittent mandatory ventilation (SIMV). STUDY DESIGN: Ventilated infants with birth weight of 500 to 1249 g were randomized at less than 6 hours of age either to pressure-limited SIMV or to PRVC on the Servo 300 ventilator (Siemens Electromedical Group, Danvers, Mass). Infants received their assigned mode of ventilation until extubation, death, or meeting predetermined failure criteria. RESULTS: Mean +/- SD birth weights were similar in the SIMV (888 +/- 199 g, n = 108) and PRVC (884 +/- 203 g, n = 104) groups. No differences were detected between SIMV and PRVC groups in the proportion of infants alive and extubated at 14 days (41% vs 37%, respectively), length of mechanical ventilation in survivors (median, 24 days vs 33 days, respectively), or the proportion of infants alive without a supplemental oxygen requirement at 36 weeks' postmenstrual age (57% vs 63%, respectively). More infants receiving SIMV (33%) failed their assigned ventilator mode than did infants receiving PRVC (20%). Including failure as an adverse outcome did not alter the overall outcome (39% of infants in the SIMV group vs 35% of infants in the PRVC group were alive, extubated, and had not failed at 14 days). CONCLUSION: In mechanically ventilated infants with birth weights of 500 to 1249 g, using PRVC ventilation from birth did not alter time to extubation.

Apgar Score↗

A longitudinal study of three brain damaged children. Infancy to adolescence.

The developmental course of three children with brain damage (now 14 to 16 years of age) was followed since early infancy in the New York Longitudinal Study. Data on behavioral characteristics, patterns of parental attitudes and practices, clinical neurological, and psychiatric evaluation, and psychometric findings at different age periods are available. Each child has shown a different behavioral course that could not be explained only in terms of motor dysfunction, intellectual deficit, patterns of parental management and attitudes, or more general features of environmental demand alone, but also required a consideration of the constellation of temperamental organization. Patterns of adaptation and levels of functioning were the complex product of the interaction of all these factors. One child developed the clinical syndrome of childhood schizophrenia.

Adolescent↗

YAC transgene-mediated olfactory receptor gene choice.

In the mouse, individual olfactory neurons express one of a thousand distinct olfactory receptor genes. Furthermore, only one allele of the expressed gene is transcribed. This phenomenon, random allelic inactivation, along with the observation that the olfactory receptor genes reside in large chromosomal arrays, suggests a role for long-range gene regulation in olfactory receptor gene choice. We have constructed a 300-kb yeast artificial chromosome (YAC) transgene in which a single receptor gene is marked while maintaining its coding region. This 300-kb piece of DNA functions as an independent olfactory receptor gene locus in directing olfactory receptor gene choice in both the olfactory system and the accessory olfactory system (vomeronasal organ, VNO). Furthermore, the transgene, like endogenous olfactory receptor loci, is subject to allelic inactivation.

Alleles↗

Temperament and follow-up to adulthood.

A follow-up of the New York longitudinal study at the 18-22-year period has been completed. Only one of the 133 subjects was not interviewed and evaluated. A temperament questionnaire for this age period has also been developed and given to 70 of the subjects. From the interview, ratings of temperament, adjustment and clinical psychiatric status were made. Statistical correlations showed significant relationships between 'difficult-easy' temperament at three and five years of age and early adult 'difficult-easy' temperament, adjustment, and presence or absence of a clinical psychiatric diagnosis. The importance of qualitative analyses of idiosyncratic developmental factors in individual cases is emphasized.

Adult↗

Phenotypic heterogeneity of human T-cell malignancies: demonstration by monoclonal antibodies and cytochemical markers.

The present study sought to delineate the phenotypic heterogeneity of the human T-cell malignancies. Twenty T-cell neoplasms were investigated for reactivity with the OKT hybridoma monoclonal antibodies and expression of acid alpha-naphthyl acetate esterase (ANAE), beta-glucuronidase (BG), and acid phosphatase (AP) activity. Twelve cases (Mycosis fungoides, Sezary syndrome, cutaneous T-cell lymphoma, chronic lymphocytic leukemia) were OKT3'T4', ie, expressed the phenotype commonly associated with mature T-helper cells. These cases were further divisible into ANAE+BG+ (6 cases), ANAE-BG+ (5 cases), and ANAE-BG- (1 case) phenotypes. In contrast to the 12 OKT3+T4+ cases, the remaining 8 cases showed considerable inter- and intratumor heterogeneity with respect to reactivity with the OKT antibodies. Six of these cases (acute lymphoblastic leukemia, lymphoblastic lymphoma) expressed phenotypes consistent with various intrathymic stages of T-cell differentiation. Five of the latter 6 cases were AP+BG+ANAE-, analogous to the majority of normal cortical thymocytes; an OKT3+T4-T8+T10+ neoplasm was ANAE+, analogous to normal medullary thymocytes. Two cases expressed the previously undescribed OKT3+T4-T8-T10+ phenotype. These studies demonstrate that the T-cell malignancies are divisible into phenotypes which correspond to normal maturational stages of T-cell differentiation and functionally distinct T-cell subsets. Phenotypic analysis of the human T-cell malignancies may provide a basis for understanding their biological heterogeneity and may aid in the identification of transitional stages of T-cell differentiation and minor T-cell subsets.

Adolescent↗

Neuropathy and anti-myelin-associated glycoprotein IgM M proteins: T cell regulation of M protein secretion in vitro.

In patients with plasma cell dyscrasia, individual clones of antibody-producing cells proliferate abnormally and secrete monoclonal antibodies or M proteins in excess. The cause of the monoclonal proliferation of lymphocytes and M protein secretion is unknown and it is not known whether the M protein-secreting B cells are autonomous or capable of responding to regulatory T cells. We carried out experiments using lymphocytes from a patient with neuropathy and plasma cell dyscrasia whose IgM M protein bound to the myelin-associated glycoprotein (MAG) to determine whether secretion of the M protein in vitro was responsive to T cell help or suppression. M protein secretion was measured by an enzyme-linked immunosorbent assay system for measuring anti-MAG IgM, and the number of M protein-secreting lymphocytes was enumerated by a reverse hemolytic plaque assay specific for the M protein idiotype. The patient's B cells were maximally stimulated by pokeweed mitogen-activated autologous OKT4+ T-helper cells and the helper effect was inhibited by OKT8+ suppressor/cytotoxic T cells. Low levels of M protein secretion in the absence of T cells were also observed and there was partial stimulation of M protein secretion by T cells in the absence of pokeweed mitogen.

Autoantibodies↗

Immunohistologic analysis of renal CD40 and CD40L expression in lupus nephritis and other glomerulonephritides.

OBJECTIVE: To investigate potential mechanisms by which CD40L-mediated signals may be involved in the pathogenesis of lupus glomerulonephritis (GN). METHODS: Renal in situ CD40L and CD40 expression was examined in patient biopsy specimens. Immunohistochemical studies were performed on frozen sections utilizing anti-CD40L monoclonal antibody (MAb), anti-CD40 MAb, or control MAb. As controls, we analyzed normal kidney specimens and specimens obtained from patients with IgA nephropathy, focal segmental glomerulosclerosis, minimal change disease, idiopathic membranous GN, and antineutrophil cytoplasmic antibody-positive pauci-immune GN. Staining distribution was noted and staining intensity scored on a semiquantitative scale of 0 (no staining) to 3+ (intense staining). RESULTS: In normal kidney, CD40 was expressed on parietal epithelial cells, mesangial cells, endothelial cells, and distal tubules but not proximal tubules. Glomerular and tubular CD40 expression was markedly up-regulated in class III and class IV lupus GN, where there was intense staining of crescents, proximal and distal tubules, and interstitial mononuclear cells. In contrast, CD40 expression in class V lupus GN was similar to that in normal kidney. Interstitial mononuclear cells expressing CD40L were present in class IV lupus GN. However, these findings were not unique to lupus GN: up-regulation of CD40 and CD40L expression was similarly observed in other inflammatory renal diseases. CONCLUSION: This study shows that CD40 is expressed on a variety of renal parenchymal and non-parenchymal cells in normal kidney. Renal CD40 expression is up-regulated in class III and class IV lupus nephritis, as well as in other inflammatory renal diseases, and is associated with the presence of CD40L+ mononuclear cells.

Adolescent↗

60-Hz electric-field effects on pineal melatonin rhythms: time course for onset and recovery.

Rats exposed for 3 weeks to uniform 60-Hz electric fields of 39 kV/m (effective field strength) failed to show normal pineal gland circadian rhythms in serotonin N-acetyl transferase activity and melatonin concentrations. The time required for recovery of the melatonin rhythm after cessation of field exposure was determined to be less than 3 days. The rapid recovery suggests that the overall metabolic competence of the pineal is not permanently compromised by electric-field exposure, and that the circadian rhythm effect may be neuronally mediated.

Animals↗

Mass spectral characteristics of derivatized metabolites of benzo [A] pyrene.

The electron impact (EI) mass spectra of the permethyl, peracetyl and per(trifluoroacetyl) derivatives of hydroxylated benzo[a]pyrene (B[a]P) metabolites were determined and the fragmentation chemistry producing the spectra elucidated. The metabolites investigated were: 3-hydroxy-B[a]P; 7,8-dihydro-7,8-dihydroxy-B[a]P; 7,8,9,10-tetrahydro-7,8,9-trihydroxy-B[a]P; and 7,8,9,10-tetrahydro-7,8,9,10-tetrahydroxy-B[a]P. In addition, the positive and negative methane chemical ionization spectra were determined for the derivatives of the BP-tetrol. The EI fragmentation patterns of the methylated metabolites that contained partially saturated rings were complex and, in the case of the di- and trimethoxy compounds, included apparent violations of the even-electron rule. The permethylated triol and tetrol cleaved through a retro-Diels-Alder reaction. The EI spectra of the peracetates were dominated by losses of acetic acid and ketene. The per(trifluoroacetyl) species fragmented by losing elements of trifluoroacetic acid, trifluoracetate radical and trifluoroacetyl. The spectra obtained from the permethylated tetrol permitted accurate prediction of the corresponding permethylated derivatives of tetrol metabolites of chrysene and benz[a]anthracene. The ability to predict spectra may be useful in trace analysis of hydrocarbon metabolites in biological samples.

Benzo(a)pyrene↗

The mass spectra of 4-aminophenanthrene and its trifluoroacetic anhydride and perfluoropropionic anhydride derivatives.

Several aminophenanthrenes have been examined with electron impact mass spectrometry. The trifluoroacetic anhydride (TFAA) and perfluoropropionic anhydride (PFPA) derivatives of 4-aminophenanthrene have been studied with electron impact as well as both positive and negative ion chemical ionization mass spectrometry utilizing methane as a reagent gas. The resulting mass spectra indicate a loss of water from the derivatives and a mechanism is proposed to account for this loss. The spectra also indicate unique fragmentation patterns associated with the position of the substituent, particularly the four position which is in the region of the molecule termed the bay region. Another interesting aspect is the spectral differences observed for the TFAA and PFPA derivatives of 4-aminophenanthrene. The positive ion chemical ionization mass spectrum of the TFAA derivative indicates an ion [M + H - H2O]+; however, the mass spectrum of the PFPA derivative of 4-aminophenanthrene indicates no water loss from the [M + H]+ ion. The negative ion chemical ionization mass spectra of the two derivatives are also very different. The mass spectrum of the TFAA derivative shows an [M - 18]- ion and the PFPA derivative shows successive losses of HF with no apparent loss of water.

Mass Spectrometry↗

Sequence and organization of the human T cell delta chain gene.

A novel human T cell receptor (TcR) gene, located 85 kbp upstream to the C alpha coding regions, was isolated using human genomic clones to identify cDNA homologous to messages encoded by this region. The deduced protein sequence of this gene is highly homologous to that of the newly identified constant region found in the murine TcR alpha chain locus. This gene undergoes rearrangements and is expressed at the RNA level in human thymocytes, peripheral T cells and several leukemic T cell lines which have been shown to express the surface gamma-delta heterodimer, suggesting that this gene encodes the human T cell delta chain.

Amino Acid Sequence↗

VH gene usage in humans: biased usage of the VH6 gene in immature B lymphoid cells.

Preferential usage of JH-proximal VH genes has been demonstrated in immature murine B cell repertoires. To determine whether this phenomenon is also evident in human repertoires, we studied utilization of VH6, the most JH-proximal human VH gene. Examination of VH gene usage in a panel of precursor B cell acute lymphoblastic leukemia samples indicated that 15% of the IgH rearrangements utilized VH6. VH6 is a single-member family in a total repertoire of 100-200 VH genes; thus, if usage were purely random, one would expect VH6 rearrangement frequency to be less than 1%. Analysis of VH gene usage in normal lymphoid tissues also revealed biased usage of VH6. VH6 was preferentially utilized in 16- to 24-week-old fetal liver as compared to adult peripheral blood mononuclear cells or spleen. Possible implications of the conservation of preferential usage of JH-proximal genes in both immature murine and human repertoires are discussed.

Adult↗

Human epidermal keratinocytes are induced to secrete interleukin-6 and co-stimulate T lymphocyte proliferation by a CD40-dependent mechanism.

Although the expression and function of CD40 on B lymphocytes has been well studied, the significance of CD40 on non-lymphoid cells such as keratinocytes (KC) is not as well characterized. We demonstrate in this report that CD40 is expressed by virtually all human KC, and that it functions as an important signaling molecule. Flow cytometry of undifferentiated and terminally differentiated KC indicated that both cell types expressed CD40, as determined by binding to monoclonal antibodies and a recombinant CD40 ligand fusion protein; interferon-gamma (IFN-gamma) treatment of KC increased CD40 expression. Cultured KC also expressed 1.5-kb CD40 transcripts. Activation of KC cell surface CD40 using the monoclonal antibody G28.5 resulted in the rapid generation of a 50-kDa tyrosine phosphorylated polypeptide, as well as a dose-dependent increase in the secretion of interleukin-6, a cytokine that has been linked to KC proliferation. KC also co-stimulated a significant T lymphocyte proliferative response to the mitogen phytohemagglutinin that was CD40 dependent. These data indicate that KC constitutively express a low level of functional CD40 and regulate their expression in response to IFN-gamma. These data support the concept that KC, via their expression of CD40, have the capacity to amplify inflammation in the skin by interacting with CD40 ligand-bearing T cells.

CD40 Antigens↗

Contribution of nitropyrene to the mutagenic activity of coal fly ash.

Stack-collected coal fly ash from western low-sulfur coal was extracted with 60:40 benzene/methanol. This extract was fractionated by preparative-scale high performance liquid chromatography (HPLC) and the mutagenic activity of 14 fractions was evaluated by microbial assay with Salmonella typhimurium TA1538. A widespread distribution of direct-acting mutagens, which probably includes both mono- and dinitroaromatics, was detected. HPLC methods were also used to isolate 1-nitropyrene from the total benzene/methanol extract. The identification of 1-nitropyrene was based on gas chromatographic and HPLC retention measurements and mass spectral data. The concentration of 1-nitropyrene in the ash extract was determined by quantitative HPLC analyses. Mutagenicity assays of the total extract and an authentic 1-nitropyrene standard with Salmonella strains TA1538, TA100, and TA98 indicated that the 1-nitropyrene accounts for approximately 0.03-0.16% of the total mutagenic activity of the extract.

Chromatography, Gas↗

APC/CTNNB1 (beta-catenin) pathway alterations in human prostate cancers.

Genetic alterations serve as beacons for the involvement of specific pathways in tumorigenesis. It was previously shown that 5% of prostate tumors harbor CTNNB1 mutations, suggesting that this tumor type may involve a deregulated APC/CTNNB1 pathway. To explore this possibility further, we searched for mutations in genes implicated in this pathway in 22 samples that included cell lines, xenografts, and primary tumors. We identified seven alterations: two in CTNNB1, three in APC, and two in hTRCP1 (also known as BTRC) which controls the degradation of CTNNB1. Alterations in the CTNNB1 regulatory domain, APC, and hTRCP1 were mutually exclusive, consistent with their equivalent effects on CTNNB1 stability. These results suggest that CTNNB1 signaling plays a critical role in the development of a significant fraction of prostate cancers. Moreover, they provide the first evidence that hTRCP1 plays a role in human neoplasia.

Animals↗