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Journal ArticleDOI

A critical review: vitamin b deficiency and nervous disease.

01 Oct 1939-Journal of Neurology, Neurosurgery, and Psychiatry (BMJ Group)-Vol. 2, Iss: 4, pp 335-360
TL;DR: The artificial synthesis of a number of the components of the vitamin B complex has made available pure crystalline material in large amounts for clinical research, and thus a milestone in the history of these affections has been passed.
Abstract: AFFECTIONS of the nervous system which result from inadequate nutrition have assumed an increasingly important position through the rapid accumulation of clinical, experimental, and pathological data. The artificial synthesis of a number of the components of the vitamin B complex has made available pure crystalline material in large amounts for clinical research, and thus a milestone in the history of these affections has been passed. It now seems appropriate to review and summarize the knowledge of these important substances. To evaluate the status of a nutritional deficiency in man is difficult. As a rule the patient induces his own disease and provides a deficiency that is not quantitatively measurable, but frequently clinical and laboratory evaluations are attempted. Both the laboratory method and the clinical method have certain advantages. Mice are not yet men and until they are the work coming -from the study of human beings is essential. Since the experience of investigators working with animals may often point the way for clinical research, we have interspersed in this review a few of the pertinent studies on the effect of nutritional deficiency on the nervous system of animals. A scheme for illustrating the multiple factors of the vitamin B complex is given in Fig. 1. To date the following portions of the vitamin B complex have been isolated and synthesized in amounts sufficient to allow for clinical trial: thiamin hydrochloride, nicotinic acid, riboflavin, and 2-methyl, 3-hydroxy, 4, 5-di (hydroxymethyl) pyridine. The deficiencies of these substances as they apply to the nervous system of man will be discussed briefly.
Citations
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Journal ArticleDOI
TL;DR: MaxQuant, an integrated suite of algorithms specifically developed for high-resolution, quantitative MS data, detects peaks, isotope clusters and stable amino acid isotope–labeled (SILAC) peptide pairs as three-dimensional objects in m/z, elution time and signal intensity space and achieves mass accuracy in the p.p.b. range.
Abstract: Efficient analysis of very large amounts of raw data for peptide identification and protein quantification is a principal challenge in mass spectrometry (MS)-based proteomics. Here we describe MaxQuant, an integrated suite of algorithms specifically developed for high-resolution, quantitative MS data. Using correlation analysis and graph theory, MaxQuant detects peaks, isotope clusters and stable amino acid isotope-labeled (SILAC) peptide pairs as three-dimensional objects in m/z, elution time and signal intensity space. By integrating multiple mass measurements and correcting for linear and nonlinear mass offsets, we achieve mass accuracy in the p.p.b. range, a sixfold increase over standard techniques. We increase the proportion of identified fragmentation spectra to 73% for SILAC peptide pairs via unambiguous assignment of isotope and missed-cleavage state and individual mass precision. MaxQuant automatically quantifies several hundred thousand peptides per SILAC-proteome experiment and allows statistically robust identification and quantification of >4,000 proteins in mammalian cell lysates.

12,340 citations

Journal ArticleDOI
01 Jul 1989-Stroke
TL;DR: A 15-item neurologic examination stroke scale for use in acute stroke therapy trials was designed and interrater reliability for the scale was found to be high, and test-retest reliability was also high, suggesting acceptable examination and scale validity.
Abstract: We designed a 15-item neurologic examination stroke scale for use in acute stroke therapy trials. In a study of 24 stroke patients, interrater reliability for the scale was found to be high (mean kappa = 0.69), and test-retest reliability was also high (mean kappa = 0.66-0.77). Test-retest reliability did not differ significantly among a neurologist, a neurology house officer, a neurology nurse, or an emergency department nurse. The stroke scale validity was assessed by comparing the scale scores obtained prospectively on 65 acute stroke patients to the patients' infarction size as measured by computed tomography scan at 1 week and to the patients' clinical outcome as determined at 3 months. These correlations (scale-lesion size r = 0.68, scale-outcome r = 0.79) suggested acceptable examination and scale validity. Of the 15 test items, the most interrater reliable item (pupillary response) had low validity. Less reliable items such as upper or lower extremity motor function were more valid. We discuss methods for improving the reliability and validity of brief examination scales to be used in stroke therapy trials.

4,769 citations

Journal ArticleDOI
TL;DR: The ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types was evaluated and suggested that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes.
Abstract: The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.

3,533 citations


Cites background from "A critical review: vitamin b defici..."

  • ...Moreover, >80% of patients with metastatic disease had detectable levels of ctDNA, higher than that reported for most conventional biomarkers (37)....

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Journal ArticleDOI
TL;DR: Current understanding of the major factors regulating protein expression is summarized to demonstrate a substantial role for regulatory processes occurring after mRNA is made in controlling steady-state protein abundances.
Abstract: Recent advances in next-generation DNA sequencing and proteomics provide an unprecedented ability to survey mRNA and protein abundances. Such proteome-wide surveys are illuminating the extent to which different aspects of gene expression help to regulate cellular protein abundances. Current data demonstrate a substantial role for regulatory processes occurring after mRNA is made - that is, post-transcriptional, translational and protein degradation regulation - in controlling steady-state protein abundances. Intriguing observations are also emerging in relation to cells following perturbation, single-cell studies and the apparent evolutionary conservation of protein and mRNA abundances. Here, we summarize current understanding of the major factors regulating protein expression.

3,308 citations

Journal ArticleDOI
TL;DR: Dopamine release in the nucleus accumbens has been linked to the efficacy of these unconditioned rewards, but dopamine release in a broader range of structures is implicated in the 'stamping-in' of memory that attaches motivational importance to otherwise neutral environmental stimuli.
Abstract: The hypothesis that dopamine is important for reward has been proposed in a number of forms, each of which has been challenged. Normally, rewarding stimuli such as food, water, lateral hypothalamic brain stimulation and several drugs of abuse become ineffective as rewards in animals given performance-sparing doses of dopamine antagonists. Dopamine release in the nucleus accumbens has been linked to the efficacy of these unconditioned rewards, but dopamine release in a broader range of structures is implicated in the 'stamping-in' of memory that attaches motivational importance to otherwise neutral environmental stimuli.

3,012 citations

References
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Journal ArticleDOI
01 Dec 1935-Brain

73 citations


"A critical review: vitamin b defici..." refers background in this paper

  • ...The peripheral neuritis in patients with pernicious anaemia cannot be distinguished pathologically (Greenfield and Carmichael, 1935) from the peripheral neuritis associated with pellagra, chronic alcoholism, and other conditions described above....

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Journal ArticleDOI
04 Feb 1939-JAMA
TL;DR: Extensive treatment of several hundred pellagrins with nicotinic acid has shown that B. influenzae can be used to measure accurately the cozymase content of the blood in normal persons and in pellAGrins.
Abstract: Growth factor V for bacilli of the influenza group has recently been identified as a codehydrogenase (cozymase or coferment).1The Lwoffs1ahave shown that bacilli of this group which require the factor cannot synthesize it from its components, nicotinic acid amide, adenylic acid, ribose and phosphoric acid. Because of the well known importance of nicotinic acid and nicotinic acid amide in the treatment of human pellagra,2it seemed important to investigate the content of factor V in the blood of pellagrins, for the cozymase of von Euler3and the coferment of Warburg4are the only two known active biologic substances in which nicotinic acid amide is found. We have shown that B. influenzae can be used to measure accurately the cozymase content of the blood in normal persons and in pellagrins. Furthermore, prolonged treatment of several hundred pellagrins with nicotinic acid has shown that in

38 citations


"A critical review: vitamin b defici..." refers background in this paper

  • ...Riboflavin (Vitamin B2) Deficiency The use of riboflavin in the human (Sebrell and Butler, 1938 ; Vilter, Vilter, and Spies, 1939) has been in conditions other than those associated with neurological disease....

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  • ...It has been shown (Vilter, Vilter, and Spies, 1939) that in severe pellagra in relapse the blood level of codehydrogenases I and II (cozymase and coferment) is below normal and that these coenzymes may be returned to their normal levels in the blood by the administration of nicotinic acid or its…...

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