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Biomedical subjects

T McNeil

Publications and source records attributed to T McNeil.

At least 19 recordsLinked to original sources
PubMed2001

Membrane-bound TNF supports secondary lymphoid organ structure but is subservient to secreted TNF in driving autoimmune inflammation.

Mice without secreted TNF but with functional, normally regulated and expressed membrane-bound TNF (memTNF(Delta/Delta) mice) were created by knocking-in the uncleavable Delta 1-9,K11E TNF allele. In contrast to TNF-deficient mice (TNF(-/-)), memTNF supported many features of lymphoid organ structure, except generation of primary B cell follicles. Splenic chemokine expression was near normal. MemTNF-induced apoptosis was mediated through both TNF-R1 and TNF-R2. That memTNF is suboptimal for development of inflammation was revealed in experimental autoimmune encephalomyelitis. Disease severity was reduced in memTNF(Delta/Delta) mice relative to wild-type mice, and the nature of spinal cord infiltrates resembled that in TNF(-/-) mice. We conclude that memTNF supports many processes underlying lymphoid tissue structure, but secreted TNF is needed for optimal inflammatory lesion development.

Animals↗
PubMed2000

Obstetric anesthesia practice in Canada.

PURPOSE: To describe obstetric anesthesia in Canada as practiced in 1997: to identify practices at variance with the literature and the opinions of experts: and to identify questions for future research. METHODS: In 1997, a detailed postal questionnaire asking about the practice of obstetric anesthesia was mailed to all 1,539 specialist anesthesiologist members of the Canadian Anaesthetists' Society residing in Canada. Nonresponders were mailed a second questionnaire three months later RESULTS: There were 865 completed questionnaires returned for analysis (56.2%). Of these, 522 anesthesiologists practiced obstetric anesthesia (60.3%). The data were subdivided into those from anesthesiologists with a full or part-time university based practice (40.1%) and those from a community based practice (59.9%). University based and community-based anesthesiologists have very similar patterns of practice. Specific areas where anesthesia practice was different from current recommendations included: (1) information provided when obtaining consent for labour epidural analgesia, (2) use of opioids and local anesthetics for initiation of epidural analgesia, (3) use of coagulation testing in preeclampsia, (4) the common use of cutting spinal needles, (5) use of neuraxial morphine and nonsteroidal anti-inflammatory agents after Cesarean deliveries, (6) optimal treatment of neuraxial opioid side effects, (7) when to insert an endotracheal tube for general anesthesia after delivery, and (8) withdrawing epidural catheters through epidural needles. CONCLUSIONS: This survey presents reference data on the practice of obstetric anesthesia in Canada in 1997. Anesthesiologists with university affiliation have very similar practices to those without university affiliations.

Analgesia, Epidural↗
PubMed2000

DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming.

DAP12 is an ITAM-bearing membrane adaptor molecule implicated in the activation of NK and myeloid cells. In mice rendered DAP12 deficient by targeted gene disruption, lymphoid and myeloid development was apparently normal, although the activating Ly49 receptors on NK cells were downregulated and nonfunctional. To analyze the consequences of DAP12 deficiency in vivo, we examined the susceptibility of DAP12-/- mice to experimental autoimmune encephalomyelitis (EAE). DAP12-/- mice were resistant to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide. Resistance was associated with a strongly diminished production of IFNgamma by myelin-reactive CD4+ T cells due to inadequate T cell priming in vivo. These data suggest that DAP12 signaling may be required for optimal antigen-presenting cell (APC) function or inflammation.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Labour and delivery complications and schizophrenia. Case-control study using contemporaneous labour ward records.

BACKGROUND: Controversy continues regarding an association between obstetric complications and risk of schizophrenia in early adult life. AIMS: To compare the rate of labour and delivery complications among persons who developed schizophrenia with controls; to establish whether any complication is associated with later schizophrenia. METHOD: We located the labour ward records of 431 individuals with schizophrenia and of same-gender controls from the same hospital birth series. Mothers were matched by age, socio-economic group and parity. Individual complications were evaluated blindly using two obstetric complication scales. RESULTS: Overall, the rate of labour and delivery complications for those who developed schizophrenia did not differ from that of controls. Males who had presented to psychiatric services before the age of 30 had a greater frequency of and more severe labour/delivery complications than their matched controls. CONCLUSIONS: Other than among young-onset males we found no increase in labour and delivery complications among cases.

Case-Control Studies↗
PubMed1999

A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells.

IL-10 is a cytokine secreted by a wide variety of cells type that has pleiotropic stimulatory and suppressive activities on both lymphoid and myeloid cells in vitro. To analyze the consequences of high IL-10 secretion by APCs in immune responses, we produced transgenic mice expressing human IL-10 directed by the MHC class II Ea promoter. Despite alterations in the development of T and B cells, no gross abnormalities were detected in peripheral lymphocyte populations or serum Ig levels. However, when immunized using conditions that give either a Th2-type or a Th1-type response, IL-10 transgenic mice failed to mount a significant T or B cell immune response to OVA. IL-10 transgenic mice were also highly susceptible to infection with intracellular pathogens like Listeria monocytogenes or Leishmania major, in contrast to IL-10 transgenic mice, where the transgene was express in T cells. Finally, the recently described stimulatory effect of IL-10 on CD8+ T cells was confirmed by the ability of IL-10 transgenic mice to limit the growth of immunogenic tumors by a CTL-mediated mechanism. These results demonstrate, that, depending on the type of immune response, IL-10 can mediate immunosuppressive or immunostimulatory activities in vivo.

Animals↗
PubMed1999

Differences in quality of life in men and women with ischemic heart disease. A prospective controlled study.

A study was conducted in Sweden in 1989-1992 to evaluate differences in quality of life (QL) in consecutive male and female patients after acute myocardial infarction (AMI), coronary artery by-pass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). Somatic and psychological dimensions of QL were assessed by self-administered questionnaire in patients one month (n = 376) and one year (n = 349) after the cardiac event. Normal controls (n = 88) were used for comparison. Differences between gender groups, as well as between study patients and controls in somatic and psychological dimensions of QL were studied. Patients were shown to experience poorer QL when compared with demographically similar controls, especially at the one-month assessment. Female patients had poorer QL after one month (in general health, feeling of arrythmia, anxiety, depression, self-esteem, experience of sex life) and after one year (general health, anxiety, depression) compared with male patients. In all dimensions of QL a proportion of patients (19-45%) experienced a decrease in QL from the one-month to the one-year assessment occasion. Healthcare workers concerned with secondary prevention must be aware that QL differs between male and female patients in several dimensions after a cardiac event. These findings should be taken into account in the clinical management of patients, particularly for female patients who may need special attention.

Aged↗
PubMed1997

HNMP-1: a novel hematopoietic and neural membrane protein differentially regulated in neural development and injury.

The hnmp-1 (hematopoietic neural membrane protein) gene encodes a protein with striking similarity to the tetra-transmembrane-spanning protein encoded by pmp22. hnmp-1 was cloned from an elutriated human monocyte library and is expressed in various human hematopoietic and lymphoid lineages as well as adult mouse spleen and thymus. In the mouse nervous system, HNMP-1 mRNA is temporally expressed by Schwann cells during sciatic nerve myelination. Dorsal root ganglia sensory and spinal cord alpha-motoneurons acquire HNMP-1 protein selectively throughout development. In the fiber tracts of the spinal cord and in sciatic nerve, HNMP-1 protein is axon-associated. Additionally a rapid and sustained level of HNMP-1 expression is observed in response to acute PNS injury. HNMP-1 is constituitively induced in sciatic nerve of Trembler J mice, which are mutant for pmp22 and have a demyelinating/hypomyelinating phenotype. The expression pattern of HNMP-1 suggests a possible role for this molecule during active myelination.

Amino Acid Sequence↗
PubMed1995

Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine.

Interleukin (IL)-7 is a potent stimulus for immature T and B cells and, to a lesser extent, mature T cells. We have inactivated the IL-7 gene in the mouse germline by using gene-targeting techniques to further understand the biology of IL-7. Mutant mice were highly lymphopenic in the peripheral blood and lymphoid organs. Bone marrow B lymphopoiesis was blocked at the transition from pro-B to pre-B cells. Thymic cellularity was reduced 20-fold, but retained normal distribution of CD4 and CD8. Splenic T cellularity was reduced 10-fold. Splenic B cells, also reduced in number, showed an abnormal population of immature B cells in adult animals. The remaining splenic populations of lymphocytes showed normal responsiveness to mitogenic stimuli. These data show that proper T and B cell development is dependent on IL-7. The IL-7-deficient mice are the first example of single cytokine-deficient mice that exhibit severe lymphoid abnormalities.

Animals↗
PubMed1995

Mice deficient for the IL-3/GM-CSF/IL-5 beta c receptor exhibit lung pathology and impaired immune response, while beta IL3 receptor-deficient mice are normal.

The receptors for IL-3, GM-CSF, and IL-5 share a common beta subunit (beta c), and mice have an additional IL-3 beta subunit (beta IL3). We have independently generated mice carrying null mutations of each molecule. beta c mutant bone marrow showed no response to GM-CSF or IL-5, whereas IL-3 stimulation of beta c or beta IL3 mutant bone marrow was normal. beta c mutant mice showed lung pathology consisting of lymphocytic infiltration and areas resembling alveolar proteinosis, and also exhibited low basal numbers of eosinophils. Infection of beta c mutant mice by Nippostrongylus brasiliensis resulted in the absence of blood and lung eosinophilia. Animals repopulated with beta c mutant bone marrow cells showed slower leukocyte recovery and reduced eosinophil numbers. These data define the role of beta c in vivo, and show a phenotype that is likely to be the cumulative effect of loss of GM-CSF and IL-5 stimulation.

Animals↗
PubMed1995

Interleukin-6-deficient mice are highly susceptible to Listeria monocytogenes infection: correlation with inefficient neutrophilia.

We have produced interleukin-6 (IL-6)-deficient mice to examine, in vivo, the wide variety of biological activities attributed to this multifunctional cytokine. To investigate the role of IL-6 during infectious disease, IL-6-deficient mice were challenged with sublethal doses of Listeria monocytogenes, a facultative intracellular bacterium. While normal control animals were able to clear the infection, mutant animals exhibited a high mortality rate and showed uncontrolled replication of the bacteria in the spleen and liver at 2 and 3 days postinfection. Sections of infected tissues showed an increase in the number and severity of inflammatory foci. All aspects of this phenotype in the mutant animals were completely reverted upon administration of recombinant murine IL-6 (rIL-6). Various parameters of natural killer (NK) cell and macrophage function were unaffected in the challenge of the mutant animals. However, IL-6-deficient animals failed to mount peripheral blood neutrophilia in response to listeriosis, whereas control animals displayed a prominent neutrophilia in the blood at 24 and 48 h postinfection. Additionally, we analyzed the efficacy of rIL-6 in protecting animals devoid of lymphocytes or devoid of neutrophils during listeriosis. Administration of rIL-6 was protective to animals devoid of lymphocytes, suggesting that the rIL-6 protective effect was not mediated through lymphocytes. In contrast, control and mutant animals depleted of neutrophils were refractory to the rIL-6 protective effect. These data suggest that IL-6 is critical early during listeriosis, perhaps acting by stimulating neutrophils either directly or indirectly. Additionally, these data show a promising therapeutic potential for rIL-6 administration during opportunistic infection.

Animals↗
PubMed1989

How do carriers of hemophilia experience prenatal diagnosis (PND)? Carriers' Immediate and later reactions to amniocentesis and fetal blood sampling.

A semistructured personal interview was performed with 29 carriers of hemophilia A or B, 1-5 years after a pregnancy in which prenatal diagnosis (PND) was performed by fetal blood sampling. Fetal blood sampling by fetoscopy was significantly more often reported by the women to the more trying than expected than was ultrasound-guided heart puncture. Of 29 women 13 was classified as having experienced the PND process (amniocentesis and fetal blood sampling) as distressing, having had mental or psychosomatic symptoms associated with it. All of the women who had abortion/miscarriage after PND reported a very high frequency of psychological sequelae during the 6 months that followed PND. Of 22 women who continued their pregnancy with a healthy fetus after PND 8 experienced the period until delivery as trying and felt that their emotional and somatic status influenced their daily life activities. This was particularly common among women who after fetoscopy received routine profylactic terbutalin treatment and had continuous sickleave until the 36th gestational week, 17/29 would consider going through PND in the future. Qualified psychological assistance must be offered both before and after PND.

Adult↗
PubMed1987

How do carriers of hemophilia experience prenatal diagnosis by fetal blood sampling?

A semistructured personal interview was performed with 29 carriers of hemophilia A or B, 1-4 years after a pregnancy in which prenatal diagnosis (PND) of hemophilia was performed by fetal blood sampling. The carriers had received different recommendations regarding future pregnancies, and 14/29 did not know before they became pregnant that PND by fetal blood sampling was possible. One third of the women felt that important information was lacking in the consultations that preceded the PND. The conclusions regarding future genetic counselling are that more attention should be paid to improving education of all female carriers before a pregnancy, to motivating fathers-to-be to attend counselling sessions with the carriers, and to emphasizing the importance of the emotional support given by the family doctor and by other females who have experienced PND.

Adult↗
PubMed1985

A risk group's visits to medical services: five years' usage of well-baby and medical clinics by a group of children with alpha 1-antitrypsin deficiency.

Visits to medical services during the first 5 years of life for 61 children with alpha 1ATD (but without liver disease) and 61 demographically similar control children without ATD were studied for frequency, diagnosis, severity of illness/complaint and extent of treatment. No significant differences were found between the ATD and control groups on any of these variables, suggesting no increased sickliness in the ATD-group and no evidence of increased parental anxiety about the child's health reflected in medical visits for little or no physical abnormality.

Child↗
PubMed1984

Offspring of women with nonorganic psychosis: infant attachment to the mother at one year of age.

Attachment to the mother at 1 year of age was studied in 46 "high-risk" offspring of index mothers with a history of nonorganic psychosis and in 80 demographically similar control offspring. Attachment was measured in the home in a standardized manner by a modified version of Ainsworth's Strange Situation procedure. Three different patterns, representing "secure attachment" (Type B), "anxiously avoidant attachment" (Type A) and "anxiously ambivalent attachment" (Type C), were defined. While no significant difference on attachment type was found between the total index versus control group, a significantly increased rate of anxious attachment (A + C) was found for offspring of schizophrenics but no other diagnostic group. Attachment type was unrelated to index mothers' psychiatric hospitalization, psychotic status and known mental disturbance during the infants' first year of life, as well as to the infants' sex.

Female↗
PubMed1984

Offspring of women with nonorganic psychosis: fear of strangers during the first year of life.

Fear of strangers ( FOS ) during the infant's first year was studied in 46 "high-risk" offspring of index mothers with a history of nonorganic psychosis and in 80 demographically similar control offspring. FOS was measured in the home by a standardized test at 1 year of age and by repeated interviews with the mother during the first year. As compared with controls, the total index group, and the subgroups of offspring of mothers with Schizophrenia and Cycloid Psychosis, significantly more often showed a total absence of FOS in the test at 1 year, as well as during the entire first year. FOS at 1 year was unrelated both to serious active psychiatric disturbance in index mothers during the infant's first year of life, and the infant's sex, in index and control groups.

Fear↗
PubMed1976

Season of birth among siblings of schizophrenics. A test of the parental conception habits interpretation.

Many studies have shown schizophrenics to be born with unusual frequency in the period January-April, and one interpretation of this seasonality of birth is that the parents of schizophrenics have an unusually strong general tendency to conceive offspring who will be born in January-April. This parental conception habits interpretation may be tested by studying whether the siblings of schizophrenics are also born with increased frequency in January-April. The present study investigated the season of birth of 288 full siblings and 44 half-siblings in 91 families of male schizophrenics. Approximately 5% of the siblings were known to be schizophrenic; with the schizophrenic siblings excluded from the analyses, the full siblings showed a birth pattern much closer (nonsignificant) to that of the schizophrenics than to that of the general population. Half-siblings showed January-April birth rates at or below the population level. Although the mechanisms responsible for the current results still remain unclear, the study suggests that seasonality of births of schizophrenics may be related to the parents' conception habits as well as to an etiological or triggering effect on the development of schizophrenia in the offspring.

Adult↗
PubMed1975

Birthrates of schizophrenics following relatively warm versus relatively cool summers.

Schizophrenics have consistently been found to be born with unusually high frequency in the early months of the calendar year. A previous study found significantly more schizophrenics to be born following warmer as contrasted with cooler summers, thus suggesting that summer temperature or a correlate of summer temperature may be an effective factor in the season of birth schizophrenia relationship. The current study re-tested the warmer vs. cooler summer finding, using both a local sample (N = 301) and a nationwide sample of Swedish schizophrenics (N = 13,440), each sample showing increased frequency of births in the early months of the year. In order to localize the possible effects of temperature to a more specific gestational period, the schizophrenics in each sample were further divided into sub-groups based upon which trimester of gestation likely occurred during the summer prior to the birth. The 71 years (1876-1946) during which the patients were born rank-ordered by mean summer temperature at representative geographical locations, and the rank-orders of years were divided into temperature quartiles. The rates of births for the total patient groups and the trimester sub-groups among both samples showed no positive linear or systematic relationship to temperature during the previous summer. Even the warmest among the 71 years were not followed by increased rates of births of schizophrenics. The results of the study did not corroborate the earlier finding.

Adult↗