Effects of CO2 and acetazolamide on bicarbonate and fluid transport in rabbit proximal tubules

Early superficial (SF) and juxtamedullary (JM) proximal convolutions of the rabbit kidney were perfused in vitro to determine the effects of carbonic anhydrase inhibition (10(-4) M acetazolamide) and acute changes in PCO2 (decreases to approximately equal to 15 and increases to approximately equal to 74 mmHg) on potential differences (PD in mV), volume reabsorption (Jv in nl x mm-1 x min-1), and bicarbonate reabsorption (JCO2 in pmol x mm-1 x min-1). At PCO2 37 mmHg early JM exhibited a more lumen-negative PD (-7.5 vs. -5.3), greater Jv (1.13 vs. 0.82), and greater JCO2 (86.7 vs. 44.4) than early Sf. Sf and JM had similar responses to acetazolamide: PD became more negative (-5.2 to -5.9 in SF; -8.8 to -10.1 in JM), Jv decreased (0.92 to 0.68 in SF; 1.11 to 0.76 in JM), and JCO2 decreased (35.7 to 7.7 in SF; 99.2 to 27.4 in JM). Increasing PCO2 to approximately equal to 74 mmHg decreased lumen-negative PD, increased Jv, and increased JCO2 in SF and JM (-5.5 to -4.8, 0.72 to 0.95, and 47.6 to 80.4 in SF; -6.6 to -5.7, 1.19 to 1.47, and 78.0 to 111.3 in JM). Decreasing PCO2 to approximately equal to 15 mmHg increased lumen-negative PD, decreased JCO2, but had no effect on Jv in both segments (-4.9 to -5.8, 51.3 to 6.3, and 0.80 to 0.79 in SF; -7.0 to -7.9, 75.3 to 19.6, and 1.34 to 1.41 in JM). It is concluded that 1) early SF and JM display quantitative heterogeneity, 2) PCO2 changes within the physiologic range produce large changes in HCO3 absorption in early proximal tubules and 3) large changes in HCO3- reabsorption are dissociated from changes in volume reabsorption during hypocapnia.     

Soluble CD14 enhances membrane CD14-mediated responses to peptidoglycan: structural requirements differ from those for responses to lipopolysaccharide

The purpose of this study was to identify the functional significance of the binding of soluble CD14 (sCD14) to bacterial peptidoglycan (PGN) and to compare the structural requirements of sCD14 for the binding to PGN and lipopolysaccharide (LPS) and for sCD14-mediated enhancement of PGN- and LPS-induced cell responses. sCD14 did not facilitate the responses of membrane CD14 (mCD14)-negative pre-B 70Z/3 cells to PGN, although it facilitated the responses of these cells to LPS and although mCD14 facilitated the responses of 70Z/3 cells to PGN. sCD14 enhanced mCD14-mediated cell activation by both PGN and LPS, but only the responses to LPS, and not to PGN, were enhanced by LPS-binding protein. Four 4- or 5-amino-acid-long sequences within the 65-amino-acid N-terminal region of sCD14 were needed for binding to both PGN and LPS and for enhancement of cell activation by both PGN and LPS. However, deletions of individual sequences had different effects on the ability of sCD14 to bind to PGN and to LPS and on the ability to enhance the responses to PGN and to LPS. Thus, there are different structural requirements of sCD14 for binding to PGN and to LPS and for the enhancement of PGN- and LPS-induced cell activation.     

Arousal responses to somatosensory and mild hypoxic stimuli are depressed during quiet sleep in healthy term infants

STUDY OBJECTIVES: To compare arousal responses to somatosensory and hypoxic stimuli in sleeping human infants and to determine whether sleep state and postnatal age exerted similar changes in these arousal responses. DESIGN: We delivered somatosensory (nasal air-jet) stimulation and mild hypoxia (15% oxygen) to 10 healthy term infants aged 2 to 4 weeks, 2 to 3 months, and 5 to 6 months during identified sleep states. Hypoxic challenges were terminated at arousal, when the oxygen saturation fell below 85%, or at 5 minutes (failure to arouse). RESULTS: Infants failed to arouse to a greater percentage of hypoxia tests during quiet sleep (QS) than during active sleep (AS) at 2 to 3 months and 5 to 6 months of age (P < 0.01). Infants failed to arouse to a greater percentage of hypoxic challenges during QS at 2 to 3 months and 5 to 6 months than at 2 to 4 weeks of age. Arousal latency to hypoxia was significantly longer in QS than in AS at each study age; however, arousal latency was not affected by postnatal age. Arousal thresholds to somatosensory stimulation were significantly greater in QS than in AS, except at 2 to 4 weeks of age. In AS, arousability to the air-jet was greater at 2 to 3 months compared to 2 to 4 weeks of age (P < 0.05); in QS it was lower at 5 to 6 months compared to 2 to 4 weeks of age (P < 0.05). Arousal latency to hypoxia and arousal thresholds to air-jet stimulation were not correlated within infants. CONCLUSION: We conclude that arousal responses of infants to somatosensory and respiratory stimuli are similarly affected by sleep state and postnatal age. Infants are less arousable to both stimulus modalities in QS than in AS, and less arousable at 5 to 6 months of age than at 2 to 4 weeks in QS.     

关于开设生物信息学课程的建议

如何获取和利用基因组和后基因组学提供的大量信息,如何具有享用全人类共有的资源的初步能力,成了当今世纪的医学生必须掌握的基本技术、知识和必须具有的初步能力,也可以说是医学教育"面向现代化、面向未来"的课程体系改革的当务之急.去掉一些相对陈旧的课程设置,在医学本科(五、八年制)开设以获取和利用基因组信息为主要目标的"生物信息学"课程,是一种解决方案.     

Antibiotic sensitivity of Mycoplasma pathogenic for man

Human pathogen mycoplasmas (Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum) are intrinsically resistant to antibiotics which inhibit the cell wall biosynthesis (beta-lactams, vancomycin, bacitracin), to polymyxins, rifamycins, sulfonamides, trimethoprim, 5-nitroimidazoles, nitrofurans and to presently available quinolones. These three species are moderately susceptible to aminoglycosides, susceptible to chloramphenicol and highly susceptible to tetracyclines. M. pneumoniae is susceptible to macrolides, lincosamins and streptogramins. M. hominis is resistant to early macrolides (erythromycin, oleandomycin, spiramycin) and susceptible to new macrolides (josamycin, midecamycin, rosaramicin), lincosamins and streptogramins. U. urealyticum is resistant to lincosamins and susceptible to macrolides and streptogramins. Discordant results from various reports can be explained by differences in methods and breakpoint concentration values. In M. pneumoniae species, two strains resistant to macrolides and lincosamins have been described. In M. hominis species, one strain resistant to tetracyclines and another one resistant to tetracyclines and chloramphenicol have been reported. Two to ten percent of U. urealyticum strains are resistant to tetracyclines. These resistances are likely to be plasmid-mediated.     

Allergic cross-reactions between cat and pig serum albumin

After observing a patient allergic to cat dander and pork but devoid of other allergies, we prospectively screened patients known to be allergic to cat for a second sensitization to pork. After collecting the sera of 10 young patients found to contain specific IgE to cat dander and pork, we undertook this study to detect the possible cross-reactive allergen, define its molecular characteristics, and evaluate its clinical relevance. Through immunoblotting techniques, cat and porcine serum albumin were found to be jointly recognized molecules. These findings were further analyzed by specific anti-albumin IgE titrations and cross-inhibition experiments. Cat serum albumin cDNA was obtained from cat liver, and the corresponding amino acid sequence was deduced and compared to the known porcine and human serum albumin sequences. Inhibition experiments showed that the spectrum of IgE reactivity to cat serum albumin completely contained IgE reactivity to porcine serum albumin, suggesting that sensitization to cat was the primary event. In two cohorts of cat-allergic persons, the frequency of sensitization to cat serum albumin was found to lie between 14% and 23%. Sensitization to porcine albumin was found to lie between 3% and 10%. About 1/3 of these persons are likely to experience allergic symptoms in relation to pork consumption. Sensitization to cat serum albumin should be considered a useful marker of possible cross-sensitization not only to porcine serum albumin but also to other mammalian serum albumins.     

Neurophysiological responses to face, facial regions and objects in adults with Asperger's syndrome: an ERP investigation.

Face processing differences have been observed between AS and control subjects at the behavioural and neurological levels. The purpose of the present study was to investigate the neurophysiological basis of processing faces and facial features (eyes and mouths) in adults with AS relative to age- and gender-matched typically-developing controls. These results were compared with ERPs generated to objects in both groups to determine if any differences were specific to facial stimuli. Although both groups elicited earlier N170 latencies to faces than to face parts and to eyes relative to mouths, adults with AS exhibited delayed N170 latencies to faces and face parts relative to controls. This difference was not observed to objects. Together these findings suggest that adults with AS may be slower to process facial information.     

Patient access to records: expectations of hospital doctors and experiences of cancer patients.

The aim of this study was to examine cancer patients' reactions to the offer of access to their medical records, hospital doctors' preconceptions of patient access to medical records and the reality of access to records for both parties. Semistructured interviews were conducted with 32 patients and 21 hospital doctors. Hospital doctors were also shown letters from their department to the general practitioner and asked about any changes they would have made as a result of knowing about patient access to records. The results showed that most patients were able to judge for themselves if they wanted access or not and that patients who chose to look at their records found access to their records helpful and reassuring even if the news was bad. Doctors expected access to records to be harmful to patients but would not have wished to amend many of the letters they had written. Patient access to records can be a safe and useful adjunct to good patient care.     

Effect of High Doses of Radiation on Human Neutrophil Chemotaxis, Phagocytosis and Morphology

Human neutrophils were exposed to varying amounts of ionizing radiation up to 1,000,000 rad and evaluated as to their ability to respond to chemotactic stimuli and phagocytize and kill bacteria. Striking morphologic and functional resistance to radiation was apparent. At doses up to 5,000 rad there was little or no impairment of chemotaxis. As the dosage increased to 50,000 rad, chemotaxis decreased to approximately 50% of nonirradiated control values. At very high doses of radiation (250,000 to 1,000,000 rad) neutrophils failed to respond significantly to chemotactic stimuli. Effects of radiation as measured by phagocytosis and the degree of ultrastructural change paralleled the chemotaxis results.     

Skin test reactivity to histamine from infancy to old age

The skin test reactivity to allergen and histamine differs according to the age of the patients, but complete data from infancy to old age are still lacking. Three hundred sixty-five subjects (1 to 85 years of age, 33.9% atopic, and 50.1% male patients) were prick tested with threefold dilutions of histamine hydrochloride (1 to 243 mg/ml). There was a significant (p less than 0.0001; F test) main effect of age on the skin reactivity to histamine. Age groups were defined and statistical analysis were performed by means of parallel line bioassay. All dose-response curves were linear and parallel. There is a significant increase in the mean wheal size between 4 to 5 and 6 to 9 years of age, 10 to 14 and 15 to 20 years. There was almost no difference between 15 to 20 and 21 to 50 years. No difference was observed between 21 to 30, 31 to 40, and 41 to 50 years, and then, the mean wheal sizes decreased significantly to reach a plateau after the age of 60 years. There was no sex difference, and skin tests with histamine were similar in atopic and nonatopic individuals.     

大学生人格特质与职业兴趣的关系研究

目的 本研究旨在探讨大学生人格特质与职业兴趣的关系.方法 对181名被试进行NEO-FFI人格测验和Holland职业兴趣测验,并对测验结果进行偏相关和多元逐步回归分析.结果 神经质与经营型存在正相关,与常规型存在负相关;外倾性与经营型存在负相关,与常规型存在正相关;开放性与研究型、艺术型存在显著的负相关,与社会型存在负相关,与常规型存在十分显著的正相关;宜人性与社会型存在十分显著的负相关;责任心与现实型、社会型和经营型存在负相关.结论 大学生人格特质与职业兴趣存在相关关系.     

To What Does the Terminal Orienting Response Respond?

Previous authors suggested that the electrodermal orienting response to stimulus onset (OR) reflects cognitive processes related to the content of a stimulus while responses to stimulus offset (TOR) reflect processes related to stimulus duration. Experiment 1 tested the hypothesis that the OR and TOR are special cases of Ss responding to whatever part of the stimulus contains information necessary to make the requested judgment. The results clearly supported this alternative hypothesis. The Ss responded to stimulus onset when asked to judge the pitch (content) of a constant tone and to stimulus offset when asked to judge the terminal pitch of a varying tone. They responded to both the onset and offset of a stimulus when asked to compare the onset and offset pitch and when asked to judge stimulus duration. Experiment 2 partially replicated Experiment 1 in an attempt to assess the OR-TOR phenomenon in a second sensory modality (vision) and with a second dependent measure. The patterns of both electrodermal and heart rate responses were similar to those of Experiment 1 and to those observed by other authors.     

Effect of the aldehyde dehydrogenase inhibitor, cyanamide, on the ex vivo sensitivity of murine multipotent and committed hematopoietic progenitor cells to mafosfamide (ASTA Z 7557)

The ex vivo sensitivity of murine multipotent (CFU-GEMM) and committed (CFU-Mk, CFU-GM, BFU-E and CFU-E) hematopoietic progenitor cells to mafosfamide was quantified with and without concurrent exposure to cyanamide, an inhibitor of aldehyde dehydrogenase activity. In the absence of cyanamide, CFU-GEMM, CFU-Mk and CFU-GM were approximately equisensitive to mafosfamide while the erythroid progenitors were more sensitive to the drug. Cyanamide potentiated the cytotoxicity of mafosfamide toward CFU-GEMM and CFU-Mk, but not toward CFU-GM, BFU-E and CFU-E. Cellular aldehyde dehydrogenases are known to catalyze the oxidation of 4-hydroxycyclophosphamide/aldophosphamide, the major intermediate in cyclophosphamide and mafosfamide activation, to the relatively nontoxic acid, carboxyphosphamide. Thus, our findings indicate that 1) murine CFU-GEMM contain the relevant aldehyde dehydrogenase activity, and 2) the relevant aldehyde dehydrogenase activity is retained upon differentiation to progenitors committed to the megakaryocytoid lineage, but lost upon differentiation to progenitors committed to the granulocytoid/monocytoid and erythroid lineages. The relative insensitivity of CFU-GM to mafosfamide is apparently due to a cellular determinant that influences their sensitivity to all cross-linking agents since CFU-GM were found to be relatively insensitive to non-oxazaphosphorine cross-linking agents as well.     

Effects of hypothalamic knife cuts on the ingestive responses to glucose and insulin.

Parasagittal knife cuts through the perifornical hypothalamus either medial or lateral to the fornix produced hyperphagia and obesity and altered the rat's ingestive responses to dilute glucose solutions. The lateral knife cut rats drank less dilute glucose solution under both nondeprived and food deprived conditions and displayed less of a feeding suppressive response to glucose ingestion compared to controls. The lateral cut rats were also deficient in their feeding response to insulin-induced hypoglycemia, although their altered sensitivity to glucose and insulin did not appear to be causally related. The medial knife cuts decreased the responsivity to glucose, but less so than the lateral cuts, and did not alter the ingestive response to insulin. Both the medial and lateral knife cuts did not appear to change the rat's responsivity to concentrated blucose solutions. The neuroanatomical and functional nature of the disorder responsible for these effects and its relationship to the hyper-phagia-obesity syndrome are discussed.     

Age, sex and individual differences in punishment sensitivity: factors influencing the feedback-related negativity

The anterior cingulate cortex (ACC) is central to evaluating performance outcomes and has been linked to individual differences in affective responses to feedback. We used electrophysiological source localization to examine the feedback-related negativity (FRN) and related ACC activity during a gambling task in relation to punishment and reward sensitivity among 16- to 17-year-old adolescents (n=20) and 18- to 29-year-old adults (n=30). The FRN was larger for monetary loss compared to win feedback and larger for high relative to low monetary value feedback, with no age differences in the FRN for win or loss feedback. Self-reported sensitivity to punishment accounted for unique variance (over sex and sensitivity to reward) in FRNs, with higher scores relating to larger FRNs and increased rostral ACC activity. These results support the ACC role in experiencing negative performance feedback, especially for individuals highly sensitive to punishment.     

Psychiatric genetics: Research challenges and pathways forward

Lessons from past psychiatric genetic research, together with key issues in psychiatry requiring genetic investigation, are reviewed in order to consider the implications for the ways forward. It is argued that traditional quantitative genetics needs to use a combination of twin, adoptee, and family strategies, to examine continuities and discontinuities in psychopathology between childhood and adult life, to compare dimensions and categories, to employ adequate conceptualization and measurement of disorders, to use statistical techniques based on latent constructs, to use biological trait indicators where possible, to examine risk factors as well as diseases, to include good measures of postulated environmental risk variables, to study the interplay between genes and environment, and to study the key assumptions underlying genetic strategies. Molecular cytogenetics needs to consider both the general and specific psychopathological risks associated with chromosome abnormalities and to examine the mechanism involved, to examine the role of submicroscopic chromosomal deletions and of mitochondrial disorders, and to investigate the mechanisms involved in trinucleotide repeat amplifications that take place during intergenerational transmission. Molecular genetics needs to make greater use of smaller pedigrees in view of the concerns over phenotypic definition and genetic heterogeneity in very large extended dense pedigrees, to use sib-pair designs in view of the likelihood that most psychiatric disorder will prove to be multifactorial, to combine association strategies with linkage analyses, to pay careful attention to the definition of phenotypes in probands, to remain in close touch with other branches of biological psychiatry, and to make effective use of collaboration between centers. To date, transgenic models have had a rather limited application in psychiatry but, despite their difficulties, they are likely to provide an underpinning for gene therapy in disorders where that seems feasible. © 1994 Wiley-Liss, Inc.     

Reducing disparities in asthma care: priorities for research--National Heart, Lung, and Blood Institute workshop report

Minority groups with diverse racial and ethnic heritages and persons living in poverty are much more likely to die of asthma and to require emergency care for exacerbations of asthma than white persons not living in poverty. The National Heart, Lung, and Blood Institute convened a multidisciplinary group of expert scientists and clinicians to review current research aimed at understanding risk factors for these disparities in asthma health outcomes, to describe key barriers to improving asthma outcomes, and to establish priorities for future research. Education programs for asthma and other chronic diseases were reviewed. Successful elements of clinic and community-based programs were identified. Factors potentially involved in producing disparities include gene-environment interaction, psychologic and social factors, and socioeconomic status. Stress potentially contributes to asthma morbidity at both the individual and community level. Recommendations are made to stimulate research to understand risk factors for disparities and their mechanisms (e.g., gene-by-environment interactions and the role of stress), to define appropriate research designs and methods for evaluating behavioral and community interventions, and to examine how differential access to care contributes to morbidity. Research is encouraged to identify strategies that improve cultural adaptation and adoption of proven programs in a variety of populations.     

Immediate allergic reactions to cephalosporins: evaluation of cross-reactivity with a panel of penicillins and cephalosporins

BACKGROUND: Allergy to cephalosporins has mainly been evaluated in the context of patients with confirmed penicillin allergy. The problem of studying cross-reactivity in subjects primarily sensitized to cephalosporins and potentially allergic to penicillins has not been sufficiently addressed. OBJECTIVE: To evaluate the in vitro IgE response and cross-reactivity to betalactams in patients with immediate allergic reactions to cephalosporins. METHODS: The study included 24 patients with immediate allergic reactions to cephalosporins and RAST-positive to at least 1 cephalosporin. Skin testing and RAST were performed with a panel of penicillins and cephalosporins. RAST inhibition assay with different monomeric conjugates of penicillin and cephalosporin was performed to establish cross-reactivity. RESULTS: The culprit cephalosporins were cefaclor (N = 7), cefonicid (N = 1), cefotaxime (N = 2), ceftazidime (N = 2), ceftriaxone (N = 3), and cefuroxime (N = 9). Two patients had a positive skin test result to penicillin determinants, and 22 patients had a negative result to penicillin determinants and tolerated benzylpenicillin administration. Of these 22, 19 had a positive skin test result to cephalosporins and divided into patients reacting only to the culprit cephalosporin (63.2%) and those reacting to more than 1 cephalosporin (36.8%). RAST and RAST inhibition studies confirmed that the side chain at the R1 position is crucial for recognition. CONCLUSION: The R1 side chain rather than the betalactam structure, shared by penicillins and cephalosporins, seems to play a dominant role in determining the specificity of immunologic reactions to cephalosporins. Thus, penicillin can be administered safely to patients allergic to cephalosporins and with a negative skin test result to penicillin determinants.     

An Upsurge in early childhood mortality in Kenya: A search for explanations

This study seeks to document recent trends in early childhood mortality in the country and to offer some plausible explanations for the upsurge in the trends. Data and information from various sources are used in this paper to achieve this purpose. The results obtained show that infant, child and under-five mortality rates had declined in the 1960s and 1970s but were taking an upward trend since early 1990s. This situation is attributable to a combination of factors, including increased poverty, adverse effects of economic hardships and cost recovery programs associated with structural adjustment programs, increased childhood malnutrition, decreased use of certain maternity care services, decline in the coverage of child immunisations, inability of the public health system to provide services, and the HIV / AIDS epidemic and the recent ethnic clashes that rocked some parts of the Rift Valley, Coast, Nyanza and Western province. In order to reverse the upward trend in mortality, there is an urgent need to intensify efforts to reduce poverty, to enable most people to have adequate food supply, improve the public health sector so that it can deliver health care to all people; to make greater efforts to raise the living standards of rural populations and improve the quality of housing, sanitary and sewerage conditions in urban slums. In addition, concerted efforts must continue to be made to contain the spread of HIV/AIDS, to assist Aids orphans and to eliminate completely and to avoid recurrence of ethnic clashes and cattle rustling.     

Immunogenicity of synthetic peptides of Haemophilus influenzae type b outer membrane protein P1.

To identify the B- and T-cell epitopes of P1 of Haemophilus influenzae type b, 13 peptides covering 90% of the protein were chemically synthesized. Mouse, guinea pig, and rabbit antisera raised against purified native P1 were tested for their reactivities against the peptides in peptide-specific enzyme-linked immunosorbent assays (ELISAs). Six immunodominant linear B-cell epitopes were mapped to residues 103 to 137, 189 to 218, 248 to 283, 307 to 331, 384 to 412, and 400 to 437 of the mature P1 protein. When P1 peptides were screened for their reactivities with three human convalescent-phase serum specimens, peptides corresponding to residues 39 to 64, 226 to 253, and 400 to 437 reacted strongly with the antisera. Four regions (residues 39 to 64, 226 to 253, 339 to 370, and 400 to 437) contained murine T-cell epitopes. Rabbit antipeptide antisera were tested for their reactivities with the immunizing peptides and P1 protein by ELISA and immunoblots. All anti-P1 peptide antisera except those raised against peptide HIBP1-8 (residues 279 to 312) or HIBP1-8-keyhole limpet hemocyanin conjugate were shown to be specific for their respective immunizing peptides by ELISA. In addition, rabbit antisera raised against the synthetic peptides corresponding to residues 1 to 29, 39 to 64, 103 to 137, 189 to 218, 226 to 253, 248 to 283, 307 to 331, and 400 to 437 of the mature P1 protein recognized the P1 protein from both typeable and nontypeable isolates. These results suggest that these peptides contain epitopes highly conserved among typeable and nontypeable strains of H. influenzae. However, none of the antipeptide antisera have bactericidal activity, nor were they protective against H. influenzae type b in the infant rat model of bacteremia.