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Biomedical subjects

B Johnson

Publications and source records attributed to B Johnson.

At least 19 recordsLinked to original sources
PubMed1992

Pleistocene geochronology and palaeothermometry from protein diagenesis in ostrich eggshells: implications for the evolution of modern humans.

Proteinaceous residues incorporated within the crystal structure of ostrich eggshells (OES) are retained without loss over geological time exceeding 10 million years. Degradation of the polypeptides, including hydrolysis to smaller peptide fragments and eventual release of free amino acids, decomposition, and racemization and epimerization occur at regular, predictable rates dependent on ambient temperature. The extent of isoleucine epimerization (aIle/Ile ratio) in OES follows linear first-order reversible kinetics in controlled-temperature laboratory simulations of time up to an aIle/Ile ratio in excess of 1.0. The hydrolysis of leucine also follows a predictable pattern, but deviates from first-order kinetics. A nonlinear mathematical model has been developed that adequately describes the pattern of leucine hydrolysis through a wide temperature range. Arrhenius parameters were derived from laboratory experiments combined with rate constant values found for 14C-dated OES from stratified caves in southern Africa. These parameters for isoleucine epimerization and leucine hydrolysis differ by ca. 10%, allowing the simultaneous solution of the two equations for temperature, independent of sample age. Although the uncertainty of the simultaneous temperature is relatively high (+/- 10 degrees C), it provides an effective means of identifying burned samples. If sample age is known, palaeotemperatures (the integrated thermal history experienced by an eggshell as opposed to an 'instantaneous' temperature) can be calculated with a precision of better than +/- 1 degrees C. The ages of levels at Border Cave, South Africa, from which anatomically modern human skeletal remains have been recovered, are dated by the extent of isoleucine epimerization in associated OES.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Does episiotomy prevent perineal trauma and pelvic floor relaxation?

OBJECTIVE: To compare the outcomes of the current practice of liberally or routinely employing episiotomy to prevent perineal tears and pelvic floor relaxation (control group) to a policy of restricting episiotomy use to specific fetal and maternal indications (experimental group). DESIGN: A randomized controlled trial (RCT). SETTING: Three university hospitals in Montreal. SUBJECTS: Seven hundred three low-risk women enrolled at 30 to 34 weeks of gestation were randomized late in labor to the designated trial arm, by parity, and followed up to 3 months postpartum. MAIN OUTCOME MEASURES: Antepartum and postpartum information on perineal trauma and pain, pelvic floor symptoms (urinary incontinence), and sexual activity was collected through the use of standard questionnaires; pelvic floor function was measured by electromyographic (EMG) perineometry. RESULTS: Restricting episiotomy use in primiparous women was associated with similar sutured perineal trauma to the liberal or routine approach. Multiparous women in the restricted episiotomy group more often gave birth with an intact perineum (31% compared with 19%, odds ratio (OR) = 1.85, 95% confidence interval (CI) = 1.09 to 3.16). All but one 3rd/4th-degree perineal tear was associated with median episiotomy (46 of 47 in primiparous women and 6 of 6 among multiparous women). No difference between trial groups was found in postpartum perineal pain, antepartum and 3-month postpartum EMG perineometry, and urinary and pelvic floor symptoms. CONCLUSIONS: We found no evidence that liberal or routine use of episiotomy prevents perineal trauma or pelvic floor relaxation. Virtually all severe perineal trauma was associated with median episiotomy. Restriction of episiotomy use among multiparous women resulted in significantly more intact perineums and less perineal suturing.

Adult↗
PubMed1992

HLA-DR2, [HLA-B7, SC31, DR2], and [HLA-B8, SC01, DR3] haplotypes distinguish subjects with asthma from those with rhinitis only in ragweed pollen allergy.

MHC haplotypes were determined for 52 patients with ragweed pollen allergy, with and without asthma, and 27 non-atopic controls. Total IgE levels were unimodally distributed in all study groups and were higher in atopic patients in general compared with non-atopics. There was no difference in total IgE levels in patients with rhinitis only compared with those with rhinitis and asthma. IgE anti-Amb a V was detected (after subtraction of values representing the means + 2 SD of the non-atopics) in 9 of 20 asthmatics but only 3 of 32 patients with only rhinitis and was thus associated with asthma. Mean anti-Amb a V was much higher in the antibody-positive asthmatics (1710 U/ml) than in the positive patients with rhinitis only (469 U/ml). The extended MHC haplotype [HLA-B7, SC31, DR2] and its possible DR-containing fragment (SC31, DR2), were found almost exclusively among the patients with IgE anti-Amb a V and were significantly elevated in patients with asthma. DR2 in general, but not DR2 without SC31, was significantly increased in frequency in patients with anti-Amb a V. In contrast, the extended haplotype [HLA-B8, SC01, DR3] and DR3 in general were increased among patients with rhinitis only and patients without IgE anti-Amb a V compared with general controls. Thus, [HLA-B8, SC01, DR3] and DR3 appear to be "protective" for the production of this antibody and the occurrence of asthma. The findings are consistent with an MHC-linked gene or genes on [HLA-B7, SC31, DR2] (but not necessarily DR2, Dw2, or DQw6 in general) controlling the IgE immune response to Amb a V and associated with asthma in ragweed pollen-sensitive subjects. In patients with rhinitis alone and generally undetectable levels of IgE anti-Amb a V, the increase in [HLA-B8, SC01, DR3] and DR3 may mark a response to an as yet unidentified Ag associated with ragweed allergy and rhinitis only.

Asthma↗
PubMed1992

Phase II trial of edatrexate in patients with advanced pancreatic adenocarcinoma.

We conducted a phase II evaluation of edatrexate in 17 previously untreated patients with advanced adenocarcinoma of the pancreas; 14 patients had at least one month of therapy. The initial dose was 80 mg/m2iv. Treatment was administered weekly for 5 weeks, then every other week. Toxicity was generally mild. The median WBC nadir was 5.4 (range 0.6-7.4) x 10(3)/microliters, and the median platelet nadir was 164.0 (range 62.0-341.0) x 10(3)/microliters. One patient died with sepsis and gastrointestinal bleeding associated with pancytopenia. Five patients had a mild rash. Nausea occurred in 6 patients, including 3 who had vomiting. In addition, 11 patients complained of vague malaise which seemed to begin within 24-48 hours after administration of edatrexate, and lasted for 2 to 3 days, resolving within 6 days of drug administration. Median survival was 85 days. Although 5 patients had stable disease, including one with relief of pain, no major responses were seen, excluding, with 95% confidence, a response rate in excess of 20%.

Adenocarcinoma↗
PubMed1992

Does ondansetron attenuate amphetamine-induced behaviour in human volunteers?

The effect of the 5-HT3 receptor antagonist, ondansetron, on the decrease in hunger produced by amphetamine was assessed in nine male volunteers using a double-blind cross-over design. Amphetamine (15 mg orally) produced a significant decrease in self-ratings of hunger 2.5 h after administration. This effect was significantly attenuated by pre-treatment with ondansetron (12 mg orally over 24 h). These findings in humans are consistent with data from animal studies suggesting that ondansetron can attenuate certain catecholamins-mediated behaviours produced by amphetamine. However, explanations founded on pharmacokinetic factors cannot be presently excluded.

Adult↗
PubMed1992

N-methyl-d,l-aspartate stimulates growth hormone and prolactin but inhibits luteinizing hormone secretion in the pig.

The effects of n-methyl-d,l-aspartate (NMA), a neuroexcitatory amino acid agonist, on luteinizing hormone (LH), prolactin (PRL) and growth hormone (GH) secretion in gilts treated with ovarian steroids was studied. Mature gilts which had displayed one or more estrous cycles of 18 to 22 d were ovariectomized and assigned to one of three treatments administered i.m.: corn oil vehicle (V; n = 6); 10 micrograms estradiol-17 b/kg BW given 33 hr before NMA (E; n = 6); .85 mg progesterone/kg BW given twice daily for 6 d prior to NMA (P4; n = 6). Blood was collected via jugular cannulae every 15 min for 6 hr. Pigs received 10 mg NMA/kg BW i.v. 2 hr after blood collection began and a combined synthetic [Ala15]-h GH releasing factor (1-29)-NH2 (GRF; 1 micrograms/kg BW) and gonadotropin releasing hormone (GnRH; .2 micrograms/kg BW) challenge given i.v. 3 hr after NMA. NMA did not alter LH secretion in E gilts. However, NMA decreased (P < .02) serum LH concentrations in V and P4 gilts. Serum LH concentrations increased (P < .01) after GnRH in all gilts. NMA did not alter PRL secretion in P4 pigs, but increased (P < .01) serum PRL concentrations in V and E animals. Treatment with NMA increased (P < .01) GH secretion in all animals while the GRF challenge increased (P < .01) serum GH concentrations in all animals except in V treated pigs. NMA increased (P < .05) cortisol secretion in all treatment groups. These results indicate that NMA inhibits LH secretion and is a secretagogue of PRL, GH and cortisol secretion with ovarian steroids modulating the LH and PRL response to NMA.

Animals↗
PubMed1992

Psychoanalysis of a man with active alcoholism.

Psychoanalysis of a man with active alcoholism, who is able to resume recreational drinking, has never been described. Mr. A. began treatment in denial of his alcoholism. Analysis demonstrated an underlying splitting between his experiencing and observing ego. His analyst received a projection of his observing ego, the part that was worried about his drinking. Because this split was resolved within a therapeutic alliance, Mr. A. decided that he had been attacking and punishing himself with alcohol, and he elected to abstain from alcohol entirely. The first key event that lead up to this dramatic decision was a sense that his analyst was a separate person. The second, arriving for discussion within the analysis through a dream, was his conviction that he would have to choose either to continue to drink with loss of control at the cost of his analysis or that he would have to choose to continue analysis at the expense of having to stop drinking. Mr. A. then came to feel that his analyst was attacking and punishing him with a fee increase. After 15 months of complete abstinence, Mr. A. found that he could drink with rare symptoms, but he still felt saddled with an abusive analyst. Mr. A.'s rages about the fee came up most commonly right after weekend or vacation breaks in the analysis. But the interpretation of these rages as related to missing me were contemptuously regarded as attempts to force him into my psychoanalytic schema rather than regarding his experience as valid. There was a dramatic shift of our alliance when Mr. A. was given complete control over the fee. I was freed to interpret and reconstruct the underlying early relationship with his parents. The final part of this article describes Mr. A.'s working-through process, which stabilized his sense of autonomy and which reconstructed his early relationship with his parents. Mr. A. became convinced that it was up to him exactly how, when, and how much to drink. Drinking too much led to consequences that he chose not to endure.

Adult↗
PubMed1992

Rice cystatin: bacterial expression, purification, cysteine proteinase inhibitory activity, and insect growth suppressing activity of a truncated form of the protein.

A cDNA clone that encodes oryzacystatin, a cysteine protease inhibitor from rice, was isolated and expressed in Escherichia coli BL-21 (DE3) using an expression plasmid under the control of a T7 RNA polymerase promoter. The construct pT7OC 9b encoded a fusion protein containing 11 amino acid residues of the NH2 terminus of the bacterial protein phi 10 and 79 residues of oryzacystatin lacking 23 NH2-terminal residues of the wild-type protein. Recombinant oryzacystatin (ROC) constituted approximately 10% of the total bacterial protein mass and was purified in a single step by anion-exchange chromatography. The inhibitory activity of ROC toward papain (Ki = 3 x 10(-8) M) was comparable with that of the naturally occurring protein isolated from rice. Caseinolytic activity in midgut homogenates from seven species of stored product insects was inhibited from 18 to 85% by ROC, whereas the same activity was inhibited from 14 to 69% by the serine proteinase inhibitor phenylmethylsulfonyl fluoride. Midguts of stored product insects apparently contain both cysteine proteinases and serine proteinases, but the relative amounts vary with the species. When fed to the red flour beetle, Tribolium castaneum, 10 wt% ROC in the diet suppressed growth approximately 35% relative to that of the control group of insects.

Animals↗
PubMed1992

Life span is shortened in BHE/cdb rats fed a diet containing 9% menhaden oil and 1% corn oil.

The effects of feeding 2 or 10% fat on glucose tolerance, blood lipids, life span and tissue pathology of male BHE/cdb rats were studied. Six groups of 30 rats were fed from weaning diets containing 1% corn oil plus either 1 or 9% corn oil (CO diets). Animals that became ill and died were necropsied and their tissues were examined histologically. Glucose tolerance and blood lipids were determined at 300 and 600 d of age. At 300, 500, 600 and 700 d of age subsets of rats were killed and heart, aorta, lungs, liver, pancreas and kidneys collected for histological examination. The experiment was terminated at 700 d. Feeding the high level MO or BT diet delayed the development of glucose intolerance and lipemia. Longevity was shorter in the rats fed the high MO diet. There were few differences among the groups of rats fed the 2% fat diets with respect to glucose tolerance and lipemia. Glomerulosclerosis was observed in all rats but was more severe and appeared earlier in rats fed the high MO diet than in those fed the high CO or BT diets. In rats with severe renal lesions, mineralized foci were observed in soft tissue, notably the aorta and heart. The results of this study indicate that the source and amount of the dietary fat can influence age-related tissue changes and longevity.

Aging↗
PubMed1992

Ondansetron, a 5-HT3 receptor antagonist, partially attenuates the effects of amphetamine: a pilot study in healthy volunteers.

Preclinical studies suggest that 5-HT3 antagonists modulate dopamine-mediated responses in the limbic system and may therefore have a therapeutic role in psychiatry. We have examined the effect of ondansetron, a specific 5-HT3 antagonist, on the psychological and psychomotor changes induced by amphetamine in human volunteers. Nine healthy males took part in this double-blind placebo-controlled balanced-crossover study. Each subject received one of three treatments in a randomised manner: (a) placebo/placebo; (b) placebo/amphetamine (15 mg); (c) ondansetron (4 mg)/amphetamine (15 mg). Subjects were assessed for self-ratings of hunger, mood, energy, alertness, restlessness, irritability, and asked to rate the abnormality of their overall subjective state. In addition, systolic blood pressure, and performance on psychomotor tests were repeatedly assessed. Although amphetamine did not cause any significant changes in self-rating of mood, energy, alterness, restlessness or irritability, it induced a significant increase in self-ratings for overall subjective state, and a significant decrease in self-ratings of hunger. Amphetamine also caused an increase in systolic blood pressure and a decrease in the mean time taken to complete the psychomotor tests. Pretreatment with ondansetron attenuated the effects of amphetamine on hunger and subjective state, but not on blood pressure or psychomotor performance tests. These findings suggest that in humans 5-HT3 receptor antagonists may partially modify the subjective effects of amphetamine, and are in keeping with results from animal studies that 5-HT3 receptor antagonists might affect neurotransmission within mesolimbic brain regions. However, it was not possible to exclude a pharmacokinetic interaction to explain the effects of ondansetron.

Adult↗
PubMed1992

Identification of the defective NADPH-oxidase component in chronic granulomatous disease: a study of 57 European families.

Chronic Granulomatous Disease (CGD) manifests as a predisposition to infection as a result of defective function of the NADPH oxidase of phagocytic cells. Proteins identified as part of this system include two subunits of a cytochrome b (cytochrome b-245) and two cytosolic factors. The affected oxidase component was determined in 63 CGD patients from 57 families, by Western blotting of extracts of their neutrophils with antibodies to those proteins. 38 (67%) of the families were X-linked with a defect of the beta subunit of the cytochrome. 13 (23%) lacked p47-phox, 3 (5%) p67-phox, and 3 (5%) the alpha subunit of the cytochrome.

Amino Acid Sequence↗
PubMed1992

Serum immunoglobulin G antibody to Porphyromonas gingivalis in rapidly progressive periodontitis: titer, avidity, and subclass distribution.

Porphyromonas gingivalis is a suspected pathogen in rapidly progressive periodontitis (RPP). We have determined the anti-P. gingivalis serum immunoglobulin G (IgG) isotype response and avidity and the subclass titer distributions for 30 RPP patients and 30 age-, sex-, and race-matched healthy subjects by using enzyme-linked immunosorbent assay technology. Patients and control subjects were classified as seropositive if their total IgG response to P. gingivalis was twofold or more than the median response in healthy subjects. The predominant antibody responses for both patients and healthy subjects were IgG2 and IgG3, with a subclass order of IgG2 greater than IgG3 greater than IgG1 greater than IgG4. The avidity of the IgG response was highest for the seropositive healthy subjects and was no different between seronegative and seropositive RPP patients. The subclass antibody responses did not depend on gender, and there were no correlations between titer, avidity, or subclass with disease severity in the RPP patients as measured by pocket depth or bone loss on dental X rays. The seronegative RPP patients exhibited antibody responses that were greater than the responses of seronegative healthy subjects for all four subclasses, while the seropositive RPP patients had higher IgG1 and IgG4 levels than seropositive healthy subjects. These findings are consistent with the hypothesis that both carbohydrate and protein antigens are important in the IgG response to P. gingivalis. The relative predominance of IgG2, a subclass which lacks strong complement fixation and opsonic properties, and the low avidity of patient anti-P. gingivalis IgG antibodies suggest that humoral responsiveness to infection with P. gingivalis may be ineffective in clearing this organism.

Adolescent↗
PubMed1992

Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis.

Cells within the synovial tissue may recruit mononuclear phagocytes into the synovial fluid and tissues of arthritic patients. We investigated the production of the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1) using sera, synovial fluid, synovial tissue, as well as macrophages and fibroblasts isolated from synovial tissues from 80 arthritic patients. MCP-1 levels were significantly higher (P less than 0.05) in synovial fluid from RA patients (mean 25.5 +/- 8.1 ng/ml [SE]) compared to synovial fluid from osteoarthritis (OA) patients (0.92 +/- 0.08), or from patients with other arthritides (2.9 +/- 1.5). MCP-1 levels in RA sera (8.44 +/- 2.33) were significantly greater than MCP-1 in normal sera (0.16 +/- 0.06). The quantities of RA synovial fluid IL-8, which is chemotactic for neutrophils and lymphocytes, and MCP-1 were strongly positively correlated (P less than 0.05). To examine the cellular source of MCP-1, RA synovial tissue macrophages and fibroblasts were isolated. Synovial tissue fibroblasts did not express MCP-1 mRNA, but could be induced to produce MCP-1 by stimulation with either IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), or LPS. In contrast, unlike normal peripheral blood monocytes or alveolar macrophages, RA synovial tissue macrophages constitutively expressed MCP-1 mRNA and antigen. Immunohistochemical analysis of synovial tissue showed that a significantly greater percentage of RA macrophages (50 +/- 8%) as compared to either OA macrophages (5 +/- 2) or normal macrophages (1 +/- 0.3) reacted with anti-MCP-1 antibodies. In addition, the synovial lining layer reacted with MCP-1 in both RA and OA synovial tissues. In contrast, only a minority of synovial fibroblasts (18 +/- 8%) from RA synovium were positive for immunolocalization of MCP-1. These results suggest that synovial production of MCP-1 may play an important role in the recruitment of mononuclear phagocytes during inflammation associated with RA and that synovial tissue macrophages are the dominant source of this cytokine.

Arthritis, Rheumatoid↗
PubMed1992

The stress of marriage to an alcoholic.

1. Historically, wives of alcoholics have been described as having disturbed, pathological personalities that were instrumental in causing and maintaining their husbands' drinking. More recently, researchers have tended to support the view that the behavior of these women reflects their stressful circumstances. 2. The women in the study reported interpersonal, extrapersonal, and intrapersonal stressors. The most frequently reported and highest ranked stressor was their relationships with their husbands. 3. Sobriety does not necessarily mean that stressors disappear. 4. More research is needed for nurses to have the knowledge necessary to help wives of alcoholics to cope with their stressors.

Adaptation, Psychological↗
PubMed1992

High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors.

We analysed the p53 open reading frame (ORF) in 16 small-cell lung cancer (SCLC) cell lines by direct sequencing of cDNA/PCR products and in 20 SCLC tumors by chemical cleavage and single-strand conformation polymorphism analyses of genomic DNA/PCR products. Abnormalities of p53 were found in 16/16 cell lines (100%) and in 16/20 tumors (80%). In the SCLC cell lines, mutations (59% missense, 18% nonsense and 23% splicing) changing the coding sequence were dispersed between amino acids 68 and 342. In the tumor samples, while the mutations occurred predominantly in exons 5-8, other mutations were located outside these regions. G to T transversions were common, occurring in 32% of the cases. We found no p53 mutations in the corresponding normal tissue from 19 patients whose tumors had p53 lesions, indicating that the mutations were all somatically acquired. In analysing the clinical data of the patients we found no correlation between tumor response to therapy or survival and the location or type of mutations. We conclude from these data that: (1) p53 mutations are found in SCLC with high frequency; (2) p53 mutations in a significant fraction of cases generate cDNAs with nonsense or splicing mutations; and (3) to date, these mutations have all been somatically acquired events.

Base Sequence↗
PubMed1992

Sudden death in ten psittacine birds associated with the operation of a self-cleaning oven.

Psittacine birds can develop severe and often fatal pneumonitis when exposed to various noxious inhalants. Toxicosis in these birds caused by inhalation of pyrolysis products produced from overheated polytetrafluoroethylene-coated cooking pans on stove tops is well known, but compounds emitted from burned foods and other materials can also be toxic. We present a case of fatal pneumonitis in 10 psittacine birds associated with the operation of an oven in the self-cleaning mode.

Air Pollution, Indoor↗