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Biomedical subjects

S Lewis

Publications and source records attributed to S Lewis.

At least 271 records · Page 15Linked to original sources

An opinion on the global impact of meat consumption.

The topic of vegetarian nutrition can be approached from several angles, perhaps one of the most important being the impact that meat production is having on the under-developed world, where ancient rain forests are being cleared to provide land for cattle grazing. Debt-burdened countries are turning over agricultural land to raise cattle and grains for feeding the cattle. These practices have resulted in less available land for the production of food, global warming because of the practices used for deforestation, exhaustion of the world's water supply, and other adverse effects on the health of the world. The consumption of meat for food is taking a toll on the consumer and the health of the world's poorest people. It is also contributing to an expanding need for foreign aid and growing world hunger.

Child↗

Arginine metabolism in experimental glomerulonephritis: interaction between nitric oxide synthase and arginase.

L-Arginine is metabolized by two pathways: 1) by nitric oxide synthase (NOS) to nitric oxide (NO) and 2) by arginase forming urea and L-ornithine. Inflammatory responses may involve a balance between the pathways, as NO is cytotoxic and vasodilatory and L-ornithine is a promoter of cell proliferation and matrix synthesis. In experimental glomerulonephritis we have previously shown that NOS is activated in nephritic glomeruli. We have now examined both pathways of L-arginine metabolism to study competition for L-arginine, temporal variation, and the sources of NOS and arginase. Acute in situ glomerulonephritis was induced in rats, and glomeruli were studied at 1, 4, and 7 days. Both NOS and arginase activities were present. There was temporal variation: NOS activity was highest on day 1 and arginase activity on day 4; both declined by day 7. Competition between the pathways was demonstrated by increased urea synthesis in the presence of NG-monomethyl-L-arginine, an inhibitor of NOS. Measurement of NOS and arginase activities in macrophages isolated from nephritic glomeruli showed that these cells were a major source of glomerular NOS but not arginase activity. In contrast, high arginase activity but low NO production was identified in cultured rat glomerular mesangial cells. These studies show differential temporal variation in expression of NOS and arginase pathways of arginine metabolism in experimental glomerulonephritis. We have found two factors that may contribute to this: 1) competition for substrate L-arginine between the two pathways and 2) different cellular sources. We hypothesize that the balance between these pathways is a mechanism regulating injury, hemodynamics, and mesangial cell proliferation.

Amino Acid Oxidoreductases↗

Ageing and balance: the measurement of spontaneous sway by posturography.

Sway was measured by static posturography in 74 healthy subjects. Four age groups were investigated: 20-40, 40-60, 60-70 and over 70 years with equal numbers of males and females in each group. Sway increased linearly with age but was not affected by gender at any age. All age groups were more dependent on proprioception than vision in the maintenance of balance, but when reliable pressoreceptor information was removed, dependence on vision increased. The relative contributions of the sensory systems to balance did not alter with advancing age. The increase in sway demonstrated with normal ageing does not appear due to altered peripheral sensibility. It is more likely that it is due to slowing of central integrative processes.

Adult↗

Low birth weight and schizophrenia.

BACKGROUND: Low birth weight has been postulated to be a risk factor for schizophrenia. METHOD: Obstetric history, premorbid adjustment, and cognitive function during admission were assessed in 167 patients with DSM-III schizophrenia or affective psychosis. RESULTS: A birth weight of less than 2500 g was significantly more common in patients with schizophrenia than in those with affective psychosis. Schizophrenic patients as a group had significantly lower mean birth weight, a finding which was particularly marked after controlling for sociodemographic confounders. In schizophrenic men, lower birth weight was highly significantly correlated with poorer premorbid social and cognitive ability, and with impairment of adult cognitive function. CONCLUSIONS: Neurodevelopmental impairment may cause poor foetal growth, and schizophrenia in adult life.

Adolescent↗

Age at onset, sex, and familial psychiatric morbidity in schizophrenia. Camberwell Collaborative Psychosis Study.

BACKGROUND: Although a genetic component in schizophrenia is well established, it is likely that the contribution of genetic factors is not constant for all cases. Several recent studies have found that the relatives of female or early onset schizophrenic patients have an increased risk of schizophrenia, compared to relatives of male or late onset cases. These hypotheses are tested in the current study. METHOD: A family study design was employed; the probands were 195 patients with functional psychosis admitted to three south London hospitals, diagnosed using Research Diagnostic Criteria (RDC), and assessed using the Present State Examination (PSE). Information on their relatives was obtained by personal interview of the mother of the proband, and from medical records. Psychiatric diagnoses were made using Family History-Research Diagnostic Criteria (FH-RDC), blind to proband information. RESULTS: There was a tendency for homotypia in the form of psychosis within families. The lifetime risk of schizophrenia in the first degree relatives of schizophrenic probands, and the risk of bipolar disorder in the first degree relatives of bipolar probands, were 5-10 times higher than reported population risks. Relatives of female and early onset (< 22 years) schizophrenic probands had higher risk of schizophrenia than relatives of male and late onset schizophrenic probands. However, this effect was compensated in part by an excess of non-schizophrenic psychoses in the relatives of male probands. CONCLUSIONS: These results suggest a high familial, possibly genetic, loading in female and early onset schizophrenia, but do not resolve the question of heterogeneity within schizophrenia.

Adult↗

STAT proteins participate in the regulation of the vasoactive intestinal peptide gene by the ciliary neurotrophic factor family of cytokines.

Ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) are members of a family of neuropoietic cytokines that have a broad range of actions on many different neuronal populations. In cultured sympathetic neurons, CNTF and LIF induce transcription of the VIP and other neuropeptide genes as part of a program of differentiation. To gain insight into the nuclear events involved in cytokine-mediated activation of the neuropeptide genes involved in neuronal differentiation, we have investigated the mechanisms of transcriptional activation of the vasoactive intestinal peptide (VIP) gene by the CNTF family of cytokines. In the neuroblastoma cell line NBFL, CNTF, LIF, and a related cytokine, oncostatin-M, activate VIP gene transcription through a 180-base pair cytokine response element (CyRE). Deletion analysis of the VIP CyRE showed that multiple regions within the 180 base-pairs are important for cytokine-mediated transcriptional activation of the VIP gene. To one of these regions within the CyRE, cytokine treatment induces binding of a protein complex composed of members of the signal transducers and activators of transcription (STAT) transcription factor family. Mutation of this STAT-binding site attenuates cytokine-mediated transcriptional activation. LIF treatment of primary sympathetic neurons also induced binding of a STAT-containing protein complex to the VIP CyRE. Thus, activation of STAT transcription factors contributes to the induction of the VIp gene by the CNTF family of cytokines and may be involved in cytokine-mediated differentiation of sympathetic neurons.

Base Sequence↗

Detection of myocardial ischemia: value of combined myocardial perfusion and cineangiographic MR imaging.

OBJECTIVE: Established noninvasive methods for assessing myocardial ischemia have limitations that might be overcome by MR imaging. We investigated MR myocardial perfusion imaging and MR ventriculography, before and after dipyridamole-induced stress, to determine whether the superior spatial and temporal resolution of MR imaging has advantages for the evaluation of myocardial ischemia. SUBJECTS AND METHODS: Eighteen patients with symptoms suggestive of myocardial ischemia were examined by use of MR perfusion imaging and MR cineangiography before and during dipyridamole-induced stress. Multiplanar gradient-echo MR cineangiography and cardiac gated fast low-angle shot (turbo-FLASH) MR imaging during injection of gadopentetate dimeglumine were used. Results were compared with findings from perfusion scintigraphy and coronary arteriography. RESULTS: The accuracy of the combination MR technique for detecting myocardial ischemia was similar to that of scintigraphy. No significant difference was found between the MR technique and scintigraphy for detecting segments of myocardium supplied by stenosed coronary arteries (> 70% reduction in diameter, as determined by coronary arteriography). The sensitivity of the combination MR technique for angiographically detecting significant coronary artery narrowing was 92%, and the specificity was 100%. For scintigraphy, the sensitivity was also 92% and the specificity was 100%. CONCLUSION: Initial results indicate that a combination of stress MR myocardial perfusion imaging and MR ventriculography is feasible and that this technique can detect myocardial ischemia with an accuracy similar to that of scintigraphy. This technique may make more complete noninvasive assessment of myocardial ischemia possible.

Adult↗

The role of parkinsonism and antiparkinsonian therapy in the subsequent development of tardive dyskinesia.

Tardive dyskinesia (TD) is a side effect of prolonged neuroleptic treatment presenting as abnormal involuntary movements. This troublesome disorder occurs in only 15-30% of patients taking neuroleptics, suggesting that these individuals may be physiologically distinct so as to be predisposed. This study analyzed possible factors contributing to TD development. Fifty patients on depot neuroleptics for more than 7.1 years were prospectively examined for TD and drug-induced parkinsonism (DIP) using the Smith-Trims rating scale for an average of 5 years. The patients were assessed for the severity of the movement and if the movement increased or decreased with respect to neuroleptic dosage, anticholinergic dosage, parkinsonism, and other related factors. Both TD and DIP increased over time. In the patients whose dose of neuroleptic decreased, the increase in TD ratings was not significant. Using a forward stepwise regression DIP was found to increase as TD worsened but did not appear to predict subsequent TD development. Anticholinergic treatment showed a less significant correlation with the change in TD. These results have implications for the management of combined TD and DIP presentation.

Adult↗

Allelic loss of IRF1 in myelodysplasia and acute myeloid leukemia: retention of IRF1 on the 5q- chromosome in some patients with the 5q- syndrome.

Acquired interstitial deletions of the long arm of chromosome 5 occur frequently in the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Recently IRF1, a putative tumor suppressor gene localized to the long arm of chromosome 5, has been shown to be deleted from the 5q- chromosome in a group of patients with MDS and AML. It has been suggested that the loss of IRF1 may be critical to the development of the 5q- syndrome. We have investigated the allelic loss of IRF1 in a group of 12 patients with MDS and a 5q deletion and 2 patients with AML and a 5q deletion. Gene dosage experiments demonstrated that 12 of 14 patients had loss of one allele of the IRF1 gene but no evidence of homozygous loss and that 2 patients with 5q- syndrome retained both copies of the gene. The retention of IRF1 on the 5q- chromosome in these two cases has been confirmed by fluorescent in situ hybridization localization using an IRF1 cosmid. Pulsed field gel electrophoresis was used to determine whether there was any evidence for structural rearrangement in the region encompassing the IRF1 gene in these two patients. No aberrant bands were detected with a range of rare cutter enzyme digests. We conclude that IRF1 maps outside the commonly deleted segment of the 5q- chromosome and that loss of IRF1 is not solely responsible for the development of the 5q- syndrome.

Adult↗

Ketorolac doses reduced.

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Anti-Inflammatory Agents, Non-Steroidal↗

Tumor necrosis factor alpha decreases 1,25-dihydroxyvitamin D3 receptors in osteoblastic ROS 17/2.8 cells.

Bone remodeling is a complex process regulated by systemic hormones, local cytokines, and growth factors. One cytokine, tumor necrosis factor alpha (TNF-alpha), is known to have potent inhibitory effects on osteoblast matrix protein production and to stimulate osteoclast recruitment. We have previously shown that TNF-alpha inhibits 1,25-(OH)2D3-stimulated synthesis of bone gla protein (BGP), an abundant and osteoblast-specific matrix constituent. We hypothesized that the mechanism of TNF-alpha action included inhibition of intracellular 1,25-(OH)2D3 receptor (VDR) number or function. To test this, the osteoblastic cell line ROS 17/2.8 was cultured in the presence or absence of TNF-alpha (100 ng/ml), and binding of [3H]1,25-(OH)2D3 to 0.3 M KCl extracts of cytosol was measured by equilibrium assay. Specific [3H]1,25-(OH)2D3 binding decreased 70%, 25 h after addition of TNF-alpha. The decrease in [3H]1,25-(OH)2D3 binding was seen by 18 h, was sustained throughout the 72 h culture period, and was greater in low-density cultures. Scatchard analysis confirmed that TNF-alpha (100 ng/ml for 24 h) caused a decrease in the number of binding sites without change in VDR affinity. Northern analysis with a VDR riboprobe revealed that the decrease in VDR occurred without a change in the 4.4 kb steady-state VDR mRNA [VDR/cyclophilin mRNA signal ratio: control, 2.25; TNF-alpha, 2.24 (24 h), 2.17 (40 h), n = 2 flasks/time point]. These results suggest that TNF-alpha action on osteoblastic cells includes an inhibitory effect on VDR number at a point distal to the synthesis of VDR mRNA.

Animals↗

Matrix-assisted laser desorption mass spectrometry of cytochromes P450.

Matrix-assisted laser desorption ionization on a time-of-flight (MALDI/TOF) mass spectrometer provides a rapid and accurate method for molecular weight determination of hydrophobic cytochrome P450 proteins (P450s). A mass accuracy of 0.075% was achieved by analysis of dialyzed P450 2B1 using bovine serum albumin (BSA) as an internal standard. The measured mass of cytochrome P450 2B2 with MALDI/TOF resulted in an average molecular weight which was higher than reported values. Immobilization procedures proved extremely effective on samples containing high concentrations of phosphate buffers.

Animals↗

Descriptive epidemiology of primary cancer of the brain, cranial nerves, and cranial meninges in New Zealand, 1948-88.

We used New Zealand data on occurrence of different types of brain cancer to investigate: (i) a possible secular increase which has been seen worldwide and has generated considerable debate; (ii) possibly higher rates among Maori; and (iii) possibly higher risks related to social class and occupation. Data from the NZ Cancer Registry on the 5,684 brain cancers diagnosed among NZ residents from 1948-88 were used to study the pattern of occurrence by gender, age, race, calendar year, social class, occupation, and histology. Age-standardized brain-cancer incidence rates per 100,000 more than doubled over the 41-year period (from 2.9 to 6.9 in males and from 2.1 to 5.1 in females). A strong trend of increasing incidence with increasing social class is seen in males (Ptrend = 0.01). Among Maori, the proportion of all brain cancer that is medulloblastoma is four times that among non-Maori, and the proportion of all brain cancers that lack histologic confirmation is about 40 percent higher. Elevated risks are seen among: dairy farmers (odds ratio [OR] = 3.4, 95 percent confidence interval [CI] = 1.9-6.0); sheep handlers (OR = 2.7, CI = 1.4-5.3); livestock workers (OR = 3.8, CI = 1.7-8.4); and farm managers (OR = 3.2, CI = 1.4-7.2); as well as among electrical engineers (OR = 8.2, CI = 20-34.7); electricians (OR = 4.6, CI = 1.7-12.2); and other electrical workers. Brain cancer rates in NZ have increased steadily since 1948, but this increase has leveled off in the most recent five-year period. Although brain cancer rates are likely to be underestimated among the Maori, an excess of medulloblastoma is evident in this group.

Adolescent↗

Surgical considerations for endosseous implants in the craniofacial region: a 3-year report.

From 1987 to 1990, 28 patients were treated with titanium implants (Brånemark flange fixtures) in the craniofacial area for the support of craniofacial prosthesis or anchorage of bone-conduction hearing aids in the Orofacial Implant Center at the University of California, Los Angeles (UCLA). A total of 88 implants were placed, of which 22 were placed in previously irradiated areas. Twenty-three of the implants were placed in the orbital area, 37 in the mastoid area, 20 in the nasal area, and eight in various other craniofacial regions. Seven implants were lost in four different patients. The proper location and positioning of implants in specific areas of the craniofacial regions, as well as soft-tissue complications and management, are discussed.

Adolescent↗

Nuclear hormone receptors involved in neoplasia: erb A exhibits a novel DNA sequence specificity determined by amino acids outside of the zinc-finger domain.

The erb A oncogene is a dominant negative allele of a thyroid hormone receptor gene and acts in the cancer cell by encoding a transcriptional repressor. We demonstrate here that the DNA sequence recognition properties of the oncogenic form of the erb A protein are significantly altered from those of the normal thyroid hormone receptors and more closely resemble those of the retinoic acid receptors; this alteration appears to play an important role in defining the targets of erb A action in neoplasia. Unexpectedly, the novel DNA recognition properties of erb A are encoded by an N-terminal region not previously implicated as playing this function in current models of receptor-DNA interaction. Two N-terminal erb A amino acids in particular, histidine 12 and cysteine 32, contribute to this phenomenon, acting in conjunction with amino acids in the zinc finger domain. The effects of the N-terminal domain can be observed at the level of both DNA binding and transcriptional modulation. Our results indicate that unanticipated determinants within the nuclear hormone receptors participate in DNA sequence recognition and may contribute to the differential target gene specificity displayed by different receptor forms.

Amino Acid Sequence↗