A novel trypsin-like enzyme in breast cancer.
Explore the source record for details and available documents.
Amino Acid Sequence↗
Biomedical subjects
J Nelson
Publications and source records attributed to J Nelson.
The detection of serine elastase in human breast cancer.
Explore the source record for details and available documents.
Amino Acid Sequence↗
B-loop analogues of human epidermal growth factor; design, expression and properties.
Explore the source record for details and available documents.
Amino Acid Sequence↗
Modification of the effect of tamoxifen, cis-platin, DTIC, and interferon-alpha 2b on human melanoma cells in culture by a mixture of vitamins.
The effect of a mixture of vitamins in modifying the efficacy of commonly used drugs in the treatment of human melanoma has not been studied. Vitamin C and d-alpha-tocopheryl succinate (alpha-TS) alone reduced the growth of human melanoma (SK-30) cells in culture, whereas beta-carotene (BC), 13-cis-retinoic acid (RA), or sodium selenite alone was ineffective. RA caused morphological changes, as evidenced by flattening of cells and formation of short cytoplasmic processes. A mixture of four vitamins (vitamin C, BC, alpha-TS, and RA) was more effective in reducing growth of human melanoma cells than a mixture of three vitamins. The growth-inhibitory effect of cis-platin, decarbazine, tamoxifen, and recombinant interferon-alpha 2b was enhanced by vitamin C alone, a mixture of three vitamins (BC, alpha-TS, and RA), and a mixture of four vitamins (vitamin C, BC, alpha-TS, and RA) that contained 50 micrograms/ml of vitamin C. These data show that a mixture of three or four vitamins can enhance the growth-inhibitory effect of currently used chemotherapeutic agents on human melanoma cells.
Ascorbic Acid↗
Viral leakage risk differences in latex condoms.
Through use of a new bacteriophage assay capable of detecting a single viral plaque-forming unit (PFU), viral leakage through multiple replicates of several types of latex condoms has been evaluated. Stocks were used that had been preserved from a previous large study in which viral leakage had been assessed preliminarily in several brands. In the present research, much larger numbers of replicates--on the order of magnitude of 100 condoms per brand--were used. Leakage was demonstrated in single production lots of each of seven brands of condoms. With one notable exception, percent leakage ranged from 0.9 to 22.8%; 100% of the specimens of one profoundly flawed brand leaked. All test condoms were subjected to conditions intended to model these prevailing during coitus. Because the condoms used in this study were aged, current stocks of two widely sold brands were tested for comparison. Of these, 11.8% of one brand leaked, 25.7% of the other. The relevance of the results, which gave a high, albeit physiologically appropriate, challenge to the test brands, is discussed--so too is the significance to condom users of results deriving from a leakage assay of exquisitely high sensitivity.
Bacteriophage phi X 174↗
Resection of large uterine septum during early pregnancy and at the oocyte retrieval--peculiarities of two cases.
Two cases of hysteroscopic metroplasties for large septate, one performed at the time of oocyte retrieval, and the second at the time of curettage for early first trimester spontaneous pregnancy loss, are reported. The peculiarities of medical circumstances and surgical approaches are discussed. Each patient had an excellent post-surgical result and a successful pregnancy. The notion that the performance of hysteroscopic surgery in women presenting with supraphysiological serum oestradiol concentrations or an early miscarriage would increase intra-operative bleeding and post-operative complications respectively is challenged by this report. The authors emphasize that thorough counselling, meticulous planning, appropriate follicular phase timing and excellent surgical techniques remain the mainstay for success.
Abortion, Spontaneous↗
Synthesis of a cyclic analogue of the C-loop region of epidermal growth factor, containing 1-aminocyclopropane-1-carboxylic acid.
We report the synthesis of a cyclic analogue of epidermal growth factor sequence 33-42 with substitution of 1-aminocyclopropane-1-carboxylic acid for glycine at position 39 (N-acetyl-Cys-Val-Ile-Gly-Tyr-Ser-ACPCA-Asp-Arg-Cys-NH2). The analogue was synthesised by solid-phase methods, using t-Boc chemistry and acid-labile side-chain protecting groups. The use of the 4-methoxybenzyl protecting group for C- and N-terminal cysteine residues resulted in the spontaneous formation of the desired intramolecular disulfide bond after HF deprotection.
Amino Acid Sequence↗
Genetic study of congenital heart defects in Northern Ireland (1974-1978).
Congenital heart defects are a major congenital abnormality and are assuming increasing importance. A study was undertaken to estimate the incidence of congenital heart defects in Northern Ireland over a five year period (1974-1978), to determine the age at diagnosis and to assess the risk of recurrence in sibs. An incidence rate of 7.3 per 1000 total births was found. This reduced to 3.1 per 1000 total births if only invasive methods of diagnosis (catheter studies, surgery, or necropsy) were considered. The overall risk of recurrence for sibs (excluding index patients with chromosomal abnormalities and syndromes) was 3.1%. In addition, excluding families with an affected parent and child gave a recurrence risk of 2.6%. By 6 weeks of age 63% of index patients had been diagnosed and this figure had risen to 88% by 1 year. This has important implications for studies which include only congenital heart defects diagnosed in the first year of life. Of 388 patients with a congenital heart defect confirmed by invasive criteria, 96 (24.7%) were found to have an extracardiac abnormality (ECA). Excluding those with epilepsy or mental handicap as the sole ECA left 91 (23.5%) with an ECA. This highlights the importance of looking for other abnormalities in a child with a congenital heart defect. The 388 index patients had 952 sibs of whom 72 (7.6%) had an ECA. Excluding those with minor abnormalities (inguinal hernias, undescended testes) as the sole ECA left 62 (6.5%) with a major ECA. In addition, excluding those with epilepsy or mental handicap as the sole ECA left 51 (5.4%) with a major ECA. Since parents are often reassured after the birth of a child with a congenital heart defect that their risk of having a child with a noncardiac abnormality is no greater than the general population this finding has important implications for genetic counselling.
Abnormalities, Multiple↗
A comparison of lesions in small intracerebral arteries among Japanese men in Hawaii and Japan.
BACKGROUND AND PURPOSE: This report examines the hypothesis that the higher risk of stroke among Japanese men in Japan compared with those in Hawaii is related to pathology in small intracerebral arteries by comparing the prevalence of such lesions in autopsied participants from two cohorts of Japanese men in Japan and Hawaii. METHODS: Existing histological sections from the left basal ganglia from 232 men from Japan and 175 men of Japanese ancestry in Hawaii were examined for selected abnormalities in arteries between 100 and 300 microns in diameter by three pathologists. The presence of lacunar infarcts was also noted, and information about cerebral infarcts, cerebral hemorrhages, and atherosclerosis in the circle of Willis was available for the Hawaii group. RESULTS: Lacunar infarcts and all small intracerebral artery lesions except medial fibrosis were more common at every age in Japan than in Hawaii. By cause of death, all lesions were three or more times more prevalent among men who died of stroke than of noncardiovascular causes in both areas. In the Hawaii group, the small intracerebral artery lesions were significantly associated with autopsy evidence of cerebral and lacunar infarcts, and with atherosclerosis in the large arteries of the circle of Willis. Among a large number of risk factors measured at the baseline examination in Hawaii, only high blood pressure and reported usual Asian diet were significantly associated with one or more measures of small intracerebral artery lesions. CONCLUSIONS: An overview of the accumulated data indicated that small intracerebral artery pathology plays an important role in the high risk of stroke in Japanese men in Japan compared with those in Hawaii. These studies support the idea that hypertension is a necessary factor in the causal pathway, but also indicate that some other factors are involved. Some aspect of an Asian diet continues to be of importance for future research.
Age Factors↗
Graft-versus-host disease following interferon therapy for relapsed chronic myeloid leukaemia post-allogeneic bone marrow transplantation.
The combination of donor leucocytes, with or without interferon, has produced encouraging responses in patients with haematological relapse following allogeneic BMT for chronic myeloid leukaemia (CML). A 25-year-old male received low-dose interferon-alpha alone for haematological relapse occurring 10 months following an allogeneic BMT for Ph-positive CML. Interferon therapy was complicated by severe GVHD requiring immunosuppressive therapy. The patient was subsequently found to be in complete haematological and cytogenetic remission, raising the possibility of an immune-mediated antileukaemic action.
Adult↗
Environmental triggers in multiple sclerosis. Fact or fallacy?
Multiple Sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. In the early, most common course of the disease there are seemingly random attacks or exacerbations usually followed by partial or complete recovery. It has long been postulated that environmental events such as infection, emotional stress, or trauma play some role in triggering exacerbations, worsening of the disease, or even the onset of MS. Indeed there have been monetary awards by the courts based on possible influence on the disease following motor vehicle accidents. This paper will describe a prospective study undertaken at the UBC MS Clinic evaluating the impact of infection, emotional stress, and physical trauma on the course of the disease in 50 relapsing-remitting patients participating in the Betaseron trial. During the first two years of the clinical trail this cohort kept diaries documenting environmental "events". The participants were evaluated clinically and with Magnetic Resonance Imaging (MRI) every six weeks. The potential triggers or events are correlated with disease activity seen on MRI, relapse occurrence and disease progression according to the neurological exam. The results of the study and their implications for patient counselling will be presented.
Environment↗
Barth syndrome: clinical features and confirmation of gene localisation to distal Xq28.
Barth syndrome is an X-linked disorder characterised by cardioskeletal myopathy of variable severity usually fatal in childhood, and neutropenia. We ascertained a large pedigree with affected males in 3 generations. All affected males had dilated cardiomyopathy, with endocardial fibroelastosis (EFE) in some. The locus for Barth syndrome in this family was found to be closely linked to DXS52 (z = 2.78, theta = 0.0). The family was nonrecombinant for DXS52 in distal Xq28, but recombinant for DXS374 which maps proximal to DXS52. This localised Barth syndrome distal to DXS374, confirming a previous localisation to distal Xq28. As yet there is no evidence for genetic heterogeneity of Barth syndrome.
Cardiomyopathies↗
Regulation of orotic acid biosynthesis and excretion induced by oral glutamine administration in mice.
Glutamine, the most abundant amino acid in blood and tissues, is degraded by the renal and splanchnic tissues, especially the small intestinal mucosa. Due to the activity of glutaminase, it may be broken down in these tissues and contribute to ammoniagenicity. Glutamine, either directly or through ammonia production, may act as a nitrogenous source for pyrimidine biosynthesis. We have evaluated the effect of glutamine on orotate metabolism in mice, by gavaging (ig) L-glutamine, 1.0 to 4.0 mmol/100 g of body wt/day, during 6 weeks of experimentation. Glutamine at doses of 2.5 to 4.0 mmol/100 g of body wt caused a significant increase in plasma ammonia and urinary orotate. The regulation of the orotic acid biosynthesis and excretion was studied by testing the effects of various inhibitors in mice force-fed with glutamine (4 mmol/100 g of body wt, ig). The orotic aciduria was insensitive to acivicin (1 and 5 mg/100 g of body wt, ip), a specific inhibitor of the cytoplasmic carbamyl phosphate synthetase-II, thus pointing toward the mitochondrion as the principal source of carbamyl phosphate. Cycloheximide (15 and 100 mg/kg of body wt, ip) caused a significant decrease in urinary orotate indicating that the induction of orotate synthesis by glutamine may be associated with the translation of a specific protein. However, orotate excretion was significantly decreased by N-(phosphonoacetyl)-L-aspartate (PALA) (5 mg/100 g of body wt, ip) due to its inhibitory effect on the aspartate transcarbamylase activity. There was a significant increase of urinary orotate following ingestion of adenine supplemented diets (0.1% and 0.2%), suggesting the blockage of the utilization of orotate for nucleotide biosynthesis by glutamine. Since orotate synthesis may also be influenced by ornithine metabolism, we evaluated the effect of glutamine administration on various ornithine-metabolizing enzymes. There was a decrease in hepatic ornithine decarboxylase activity with no change in hepatic ornithine aminotransferase activity following the administration of glutamine. This observation indicates that an increased metabolic utilization of ornithine is not responsible for the increase in orotate excretion, which may be caused principally through an effect of glutamine on mitochondrial carbamyl phosphate synthesis.
Administration, Oral↗
Structure-activity relationships leading to WAY-121,520, a tris aryl-type, indomethacin-based, phospholipase A2 (PLA2)/leukotriene biosynthesis inhibitor.
We were intrigued by reports of the inhibition of phospholipase A2 (PLA2) by indomethacin. In order to increase the potency of the indomethacin system as an inhibitor of PLA2, it was decided to make more lipophilic analogs. Indeed, covalent attachment of a quinoline ring to the methoxy substituent of indomethacin affords WAY-122,220 which is almost an order of magnitude more potent than indomethacin in inhibiting human synovial fluid PLA2 (IC50 = 15 and 145 microM, respectively). The N-p-chloro-benzyl analog of this compound, WAY-121,520, was an even more potent inhibitor of PLA2 (IC50 = 4 microM). Structural analyses and molecular modeling suggest that these compounds may inhibit PLA2 by mimicking arachidonic acid. WAY-121,520 is also a potent leukotriene biosynthesis inhibitor both in the rat PMN and mouse macrophage assays (IC50 = 10 and 4 nM, respectively), possibly acting via a 5-LO (5-lipoxygenase) translocation inhibition mechanism. The multiple actions of WAY-121,520 may contribute to its favorable anti-inflammatory profile.
Animals↗
The effects of various inhibitors on the regulation of orotic acid excretion in sparse-fur mutant mice (spf/Y) deficient in ornithine transcarbamylase.
Experiments were conducted to determine whether the excessive orotic aciduria, induced in sparse-fur male mice (spf/Y) deficient in ornithine transcarbamylase (OTC), may be regulated by some inhibitors, such as acivicin (0.014 mmol/100 g body weight, i.p.), N-(phosphonoacetyl)-L-aspartate (PALA, 2.5 mg/100 g body weight, i.p.), adenine (3 g/kg diet) and cycloheximide (0.35 mmol/kg body weight, i.p.). We also administered ornithine (1 mmol/100 g body weight, i.p.), a substrate of the urea cycle, to alleviate the metabolic deficiency of arginine in spf/Y mice which may also be responsible for excessive orotic aciduria. The orotic aciduria remained insensitive to acivicin, indicating mitochondria as the source of carbamyl phosphate. However, orotate excretion was significantly decreased by PALA (P < 0.01), due to its effect on the aspartate transcarbamylase activity. The ingestion of adenine resulted in an increase (P < 0.05) of urinary orotate, suggesting the blockage of the utilization of orotate for nucleotide biosynthesis. Ornithine administration led to a reduction (P < 0.01) of the excretion of orotate induced by the OTC deficiency in these mice, indicating that one of the regulatory steps in its synthesis may be the availability of ornithine. There were no changes in urinary orotate excretion in spf/Y mice when treated with cycloheximide. On the other hand, pretreatment with cycloheximide in an artificial model of OTC deficiency (Swiss-ICR normal mice on an arginine-deficient diet treated thereafter with norvaline, an inhibitor of OTC), caused a significant decrease in urinary orotate. These results suggest that spf/Y mice are unique in that the increased synthesis of orotate is not sensitive to cycloheximide. Perhaps this may reflect an adaptive phenomenon developed by the mutant mice to handle excess mitochondrial carbamyl phosphate and orotic acid.
Adenine↗
Use of vacuum tumescence device for impotence secondary to venous leakage.
The causes and treatment of venogenic impotence are still controversial. From September 1989 to April 1991, 317 men complaining of impotence were evaluated in our Erectile Dysfunction Clinic. Seventy patients were suspected of having venous leakage, and all men had dynamic cavernosography performed. Forty-seven of these 70 men (67%) had venous leakage, and a vacuum tumescence device was recommended as initial treatment for all of them. A questionnaire was later mailed to all 47 patients. A response to the questionnaire was obtained from 45 men (96%). Twenty-nine patients had purchased a vacuum tumescence device (Osbon ErecAid). A satisfactory result was obtained in 20 patients (69%) with venous leakage. Since the use of the vacuum tumescence device is relatively safe and noninvasive, and the results are as good as or better than venous ligation, we recommend its use as the initial treatment of venogenic impotence until a consistently reliable treatment for this condition is found.
Erectile Dysfunction↗
Failure of the legal system to enforce drunk driving legislation effectively.
STUDY OBJECTIVE: To evaluate the investigation and prosecution of drunk drivers and identify reasons for system failure. DESIGN: Prospective data collection on all drivers with an elevated blood alcohol level who were treated at a Level I trauma center between January 1 and June 30, 1991. SETTING: Level I trauma center/university medical center serving a population of 1.8 million. INTERVENTIONS: Prospective data collection, interviewing ambulance squad members, investigating police, and results of prosecution. MEASUREMENTS AND MAIN RESULTS: Of 321 drivers, 78 had ethanol levels of more than 100 mg/dL; nine were between 50 and 100 mg/dL. All drivers had rapid transport to a trauma center for severe injury or high-risk injury mechanism. Police reports were accessible for 84 of 87 drivers; all drivers were believed to be at fault. The crashes resulted in five deaths and 74 other victims requiring hospitalization. Six of the intoxicated drivers died. Police requests for blood alcohol levels were made for 28 drivers, one of whom died. The remaining 59 drivers had no legal blood alcohol level drawn. Although the greater the distance from our center (more rural), the less likely were requests for ethanol levels, but there were many "no requests" from nearby cities. Of the 28 drivers on whom legal alcohol levels were drawn, eight escaped central registration with the highway safety commission, which records any and every traffic violation within New Jersey. Of the remaining 20, eight were not prosecuted (excluding one death), including one repeat offender. One committed a later "driving while intoxicated" offense and was then prosecuted. The remaining 11 were all convicted; five were repeat offenders. CONCLUSION: Reasonable cause is required for legal blood alcohol requests. Our data demonstrated that this is difficult when the driver is unavailable for questioning. However, once legal blood alcohol levels have been obtained, inadequate legal follow-up leads to nonprosecution. Once officially charged, conviction appears certain, but even this punishment and re-education fail to change behavior in many of these drivers.
Accidents, Traffic↗
Persuasion and economic efficiency. The cost-benefit analysis of banning abortion.
Explore the source record for details and available documents.
Abortion, Induced↗