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Showing papers by "University of Alabama at Birmingham published in 1986"


Journal ArticleDOI
TL;DR: Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes and these proposed criteria utilize classification trees, or algorithms.
Abstract: For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. Comparison diagnoses included rheumatoid arthritis and other painful conditions of the knee, exclusive of referred or para-articular pain. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms.

6,160 citations


Journal ArticleDOI
TL;DR: It is concluded that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis and patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acy Clovir treatment.
Abstract: We randomly assigned 208 patients who underwent brain biopsy for presumptive herpes simplex encephalitis to receive either vidarabine (15 mg per kilogram of body weight per day) or acyclovir (30 mg per kilogram per day) for 10 days. Sixty-nine patients (33 percent) had biopsy-proved disease; 37 received vidarabine, and 32 acyclovir. The mortality in the vidarabine recipients was 54 percent, as compared with 28 percent in the acyclovir recipients (P = 0.008). Six-month mortality varied according to the Glasgow coma score at the onset of therapy. For scores of greater than 10, 7 to 10, and less than or equal to 6, mortality was 42, 46, and 67 percent in the patients treated with vidarabine, as compared with 0, 25, and 25 percent in those treated with acyclovir. A six-month morbidity assessment using an adapted scoring system revealed that 5 of 37 patients receiving vidarabine (14 percent) as compared with 12 of 32 receiving acyclovir (38 percent) were functioning normally (P = 0.021). Eight vidarabine-treated patients (22 percent) and three acyclovir-treated patients (9 percent) had moderate debility. Patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acyclovir treatment. We conclude that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis.

772 citations


Journal ArticleDOI
TL;DR: In this article, a completely parametric system is presented for the decomposition of time-varying patterns of risk into additive, overlapping phases, descriptively labeled as early, constant-hazard, and late.
Abstract: The hazard function of time-related events, such as death or reoperation following heart valve replacement, often is time-varying in a structured fashion, as is the influence of risk factors associated with the events. A completely parametric system is presented for the decomposition of time-varying patterns of risk into additive, overlapping phases, descriptively labeled as early, constant-hazard, and late. Each phase is shaped by a different generic function of time constituting a family of nested equations and is scaled by a separate logit-linear or log-linear function of concomitant information. Model building uses maximum likelihood estimation. The resulting parametric equations permit hazard function, survivorship function, and probability estimates and their confidence limits to be portrayed and adjusted for concomitant information. These provide a comprehensive analysis of time-related events from which inferences may be drawn to improve, for example, the management of patients with valva...

616 citations


Journal ArticleDOI
01 Aug 1986-Science
TL;DR: The findings demonstrate the presence of chloride channels in the apical membranes of CF airway cells, which appears to be intact, but cyclic adenosine monophosphate (cAMP)-dependent control of their activity is defective.
Abstract: In many epithelial cells the chloride conductance of the apical membrane increases during the stimulation of electrolyte secretion. Single-channel recordings from human airway epithelial cells showed that beta-adrenergic stimulation evoked apical membrane chloride channel activity, but this response was absent in cells from patients with cystic fibrosis (CF). However, when membrane patches were excised from CF cells into media containing sufficient free calcium (approximately 180 nanomolar), chloride channels were activated. The chloride channels of CF cells were similar to those of normal cells as judged by their current-voltage relations, ion selectivity, and kinetic behavior. These findings demonstrate the presence of chloride channels in the apical membranes of CF airway cells. Their regulation by calcium appears to be intact, but cyclic adenosine monophosphate (cAMP)-dependent control of their activity is defective.

574 citations


Journal ArticleDOI
TL;DR: The CES-DC showed poor reliability and validity in the children alone but had good psychometric properties for the adolescents, and more validational research is required before standard clinical use can be recommended.
Abstract: Psychometric characteristics of the Center for Epidemiological Studies Depression Scale for Children (CES-DC) were evaluated with 148 child and adolescent psychiatric inpatients. Test-retest reliability, internal consistency, and concurrent validity were adequate. Principal components analysis identified three distinct factors: behavioral and cognitive components of depression and a happiness dimension. However, subsequent factor scores and CES-DC total scores were unable to discriminate DSM-III diagnoses, including depressive and nondepressive categories. The CES-DC showed poor reliability and validity in the children alone but had good psychometric properties for the adolescents. More validational research is required before standard clinical use can be recommended.

554 citations


Journal ArticleDOI
26 Sep 1986-Cell
TL;DR: The C.B-17scid mutation may adversely affect the recombinase system catalyzing the assembly of antigen receptor genes in developing B and T lymphocytes.

521 citations


Journal ArticleDOI
09 May 1986-Cell
TL;DR: While MPMV-like viruses cannot be used as direct models for the AIDS/SAIDS associated with lentiviruses, they provide an important system for studying the molecular basis of immunosuppressive diseases in primates.

338 citations


Journal Article
TL;DR: Tumor infiltrating lymphocytes isolated from metastatic melanoma patients were predominantly cytotoxic T-lymphocytes with the ability to recognize and kill autologous tumor cells after in vitro culture; interleukin 2 induced proliferation of TIL and augmented their cytot toxic activity such that they eliminated autologus tumor cells.
Abstract: Tumor infiltrating lymphocytes (TIL) were isolated from 22 tumors obtained from 15 patients with metastatic melanoma. In 18 of the 22 tumors, a substantial number of lymphocytes was isolated with an average lymphoid cell:tumor cell ratio of 1.26. The TIL were predominantly cytotoxic/suppressor T-lymphocytes with an average of 87% Leu4+, 61% Leu2a+, and 18% Leu3a+ cells. There were less than 2% natural killer cells, B-cells, or macrophages. An average of 3.8% (range, less than 0.1 to 8.6%) of freshly isolated TIL bound to autologous tumor cells. Prior to culture, none of the tumor-binding cells (TBC) was cytotoxic as judged by trypan blue exclusion. The frequency of TBC increased to 11.6% after 2 days of culture, and 10% of these TBC developed cytotoxic activity. When interleukin 2 was added to cultures, the frequency of TBC increased, and the frequency of cytotoxic TBC was 2-fold higher compared to control cultures. After 10 days of culture with interleukin 2, TIL increased in number with a concomitant disappearance of tumor cells, whereas there were severe decreases of lymphocytes and no decrease of tumor cells in control cultures. TIL were cultured for 8 to 10 days with recombinant interleukin 2 and tested for cytotoxicity against autologous and allogenic tumor cells and K562 targets in a 4-h 51Cr release assay. rIL2-cultured TIL from all nine patients tested exhibited the highest levels of lysis against autologous tumor cells. Of the nine TIL samples, five exhibited an apparent specificity for autologous melanoma, while four specimens killed both allogenic and autologous melanoma. The ability of TIL to kill K562 targets appeared to parallel the ability to kill allogenic targets. For comparison, recombinant interleukin 2-cultured peripheral blood mononuclear cells from the same patients were assayed for cytotoxic activity against autologous and allogenic melanomas. Unlike some TIL, none of the peripheral blood mononuclear cells exhibited specificity for autologous tumor cells. In summary, TIL isolated from metastatic melanoma patients were predominantly cytotoxic T-lymphocytes with the ability to recognize and kill autologous tumor cells after in vitro culture; interleukin 2 induced proliferation of TIL and augmented their cytotoxic activity such that they eliminated autologous tumor cells.

274 citations


Journal ArticleDOI
01 May 1986-Cancer
TL;DR: The addition of cisplatin improves the chemotherapy of advanced ovarian carcinoma, and the response duration for patients with measurable disease and progression‐free interval for all patients showed a statistically significant advantage for CAP; however, there was no difference in survival of patients with nonmeasurable disease.
Abstract: A randomized clinical trial was conducted in women with bulky (suboptimal) Stage III and Stage IV ovarian carcinoma, using doxorubicin (Adriamycin) and cyclophosphamide with or without cisplatin. There were 440 evaluable cases, of which 227 had measurable disease. One hundred twenty of these latter patients were treated with cyclophosphamide and doxorubicin (CA), while 107 received cyclophosphamide, doxorubicin and cisplatin (CAP). The clinical complete response (CR) rate for CA was 26% (31/120) compared with 51% (55/107) for CAP (P = less than 0.0001). Of 23 CRs receiving CA who had a second-look laparotomy, only four were negative; of 39 CRs receiving CAP and a second-look, 13 were negative (not statistically significant). The response duration for patients with measurable disease (median 14.6 versus 8.8 months), progression-free interval for all patients (13.1 versus 7.7 months), and survival for patients with measurable disease (19.7 versus 15.7 months) showed a statistically significant advantage for CAP; however, there was no difference in survival of patients with nonmeasurable disease. Toxicity was more severe with CAP but was tolerable. Thus, the addition of cisplatin improves the chemotherapy of advanced ovarian carcinoma.

272 citations


Journal ArticleDOI
TL;DR: The research indicates that bryostatin, a macrocyclic lactone that binds to the phorbol ester receptor in human polymorphonuclear leukocytes, also binds to this receptor in the human promyelocytic leukemia cell line, HL-60, and suggests that some of the biologic effects of ph orbol esters may occur through a more complex mechanism than previously thought.
Abstract: Phorbol esters bind to and activate a calcium phospholipid-dependent protein kinase (C kinase). Some researchers believe that activation of C kinase is necessary for the induction of phorbol ester biologic effects. Our research indicates that bryostatin, a macrocyclic lactone that binds to the phorbol ester receptor in human polymorphonuclear leukocytes, also binds to this receptor in the human promyelocytic leukemia cell line, HL-60. Bryostatin activates partially purified C kinase from HL-60 cells in vitro, and when applied to HL-60 cells in vivo, it decreases measurable cytoplasmic C kinase activity. Unlike the phorbol esters, bryostatin is unable to induce a macrophage-like differentiation of HL-60 cells; however, bryostatin, in a dose-dependent fashion, blocks phorbol ester-induced differentiation of HL-60 cells and, if applied within 48 hr of phorbol esters, halts further differentiation. These results suggest that activation of the C kinase by some agents is not sufficient for induction of HL-60 cell differentiation and imply that some of the biologic effects of phorbol esters may occur through a more complex mechanism than previously thought.

262 citations



Journal ArticleDOI
TL;DR: The prognostic value of the Indiana staging system was prospectively validated in this study and was subsequently prospectively used in SECSG protocol GU 81 332, a study randomizing patients to remission induction therapy with PVB v cisplatin, VP-16, and bleomycin.
Abstract: Between 1978 and 1982, 180 patients from Indiana University (Indianapolis) were entered on the Southeastern Cancer Study Group (SECSG) protocol 78 GU 240, a randomized comparison of cisplatin, vinblastine, and bleomycin (PVB) v PVB plus doxorubicin induction chemotherapy regimens, with a second randomization to maintenance vinblastine v no further therapy. One hundred forty-eight of these patients obtained a favorable response to chemotherapy, defined as a complete response (CR) or a surgical resection of teratoma. The prognostic significance of various patient characteristics was investigated using the logistic regression model. Two classifications for the extent of disease were considered: the Indiana staging system and the M.D. Anderson (MDA) staging system. The Indiana staging system had the greater prognostic significance. This staging system allowed the population to be split into three groups (minimal, moderate, advanced disease) in which the observed proportions of favorable responders were 99%, 9...

Journal ArticleDOI
TL;DR: hypertrophy of the ventricular main chamber was a risk factor for death in both the early and late phases of hazard, which explained in part the lesser risk of the Fontan operation in patients with tricuspid atresia.

Journal ArticleDOI
01 Jun 1986-Nature
TL;DR: It is reported that recombinant human IL-2 influences the growth of glial cells—specifically, the proliferation and differentiation of oligodendrocytes and may have a role in the inflammatory neural lesions of multiple sclerosis patients and in the growing of brain glia during injury or disease.
Abstract: There exists considerable evidence that the growth of glial cells can be influenced by T-cell-derived lymphokines and monokines. Astrocytes proliferate in the presence of mitogen- or antigen-stimulated T-cell supernatants1–3, supernatants from human T-lymphotropic virus (HTLV)-transformed T cells3, and purified human interleukin-1 (IL-1; ref. 4). Oligodendrocytes proliferate and differentiate when incubated with supernatants from mitogen-activated or HTLV-transformed T cells3. In addition, we have recently purified a T-cell-derived lymphokine of relative molecular mass 30,000, termed glial growth promoting factor (GGPF), which specifically stimulates the proliferation of oligodendrocytes5. The traditional role of interleukins 1 and 2 is in the initiation, propagation and regulation of the immune response6. IL-1, released by a variety of cells including monocytes, stimulates T cells to produce IL-2 (ref. 7); IL-2 in turn induces the expansion of T cells that is critical for immune responsiveness. Recently, IL-2 has been shown to induce B-cell proliferation8,9 and immunoglobulin secretion10, indicating that its action is not restricted to T cells. We now report that recombinant human IL-2 influences the growth of glial cells—specifically, the proliferation and differentiation of oligodendrocytes. IL-2 may have a role in the inflammatory neural lesions of multiple sclerosis patients and in the growth of brain glia during injury or disease.

Journal ArticleDOI
TL;DR: In this article, polysaccharide chains composed of a simple, repeating disaccharide unit are modified after synthesis in less than 30 seconds, into a heterogeneous mixture of variously sulfated, complex carbohydrate sequences.

Journal ArticleDOI
TL;DR: It is proposed that in humans monomeric serum IgA may protect endogenous antigens expressed on various cells and tissues by preventing their interaction with humoral and cellular immune mechanisms that may lead to tissue damage.

Journal ArticleDOI
TL;DR: Correlational and experimental evidence of the Face Scale's construct validity is presented, as well as its test-retest reliability, and recommendations are made for its use as a screening tool and for additional validity studies.
Abstract: Validity and reliability studies were conducted on the Face Scale, a very brief, pictorial scale of mood which uses a sequence of 20 faces and does not require reading literacy. Correlational and experimental evidence of the Face Scale's construct validity is presented, as well as its test-retest reliability. Recommendations are made for its use as a screening tool and for additional validity studies.

Journal ArticleDOI
TL;DR: The academic achievement scores of 122 children with epilepsy were examined in relation to demographic and clinical seizure variables, and the strongest correlates of academic performance were age of the child, age of seizure onset, lifetime total seizure frequency, and presence of multiple seizures.
Abstract: The academic achievement scores of 122 children with epilepsy were examined in relation to demographic and clinical seizure variables. As a group, these children were making less academic progress than expected for their age and IQ level. Academic deficiencies were greatest in arithmetic, followed by spelling, reading, comprehension, and word recognition. Results of the multiple regression analyses indicated a modest combined predictive significance of the demographic and clinical seizure variables for academic performance. In addition, the magnitude of these relationships varied by academic area. Among the individual variables examined the strongest correlates of academic performance were age of the child, age of seizure onset, lifetime total seizure frequency, and presence of multiple seizures (absence and tonic-clonic). These results are discussed in relation to developing an understanding of the factors which underlie academic vulnerability in children with epilepsy.

Journal ArticleDOI
TL;DR: This paper explored the relationship between liberalism, victimization experience (both direct and vicarious), fear of victimization, and attitudes towards purposes of incarceration and found that both fear and liberalism contribute to punitiveness.
Abstract: This paper explores the relationship between liberalism, victimization experience (both direct and vicarious), fear of victimization, and attitudes towards purposes of incarceration. The study makes use of a national public opinion poll conducted for ABC News in 1982. The major findings are that both fear and liberalism contribute to punitiveness but, more importantly, individual demographic characteristics are ambiguously related to punitiveness. It appears that demographic characteristics are related to punitiveness through a complex of other attitudinal associations—in this instance, fear and liberalism. Neither direct nor vicarious victimization had a direct effect on punishment attitudes. To the extent that victimization experience affects punitiveness, the effects are indirect through fear.

Journal ArticleDOI
TL;DR: In this article, microbial biomass, community structure and activity were determined in the subsurface horizons of four contrasting soil types common to Alabama, and the results indicated that the vertical distribution of microorganisms in a soil profile differs greatly as a function of soil type.
Abstract: Microbial biomass, community structure and activity were determined in the subsurface horizons of four contrasting soil types common to Alabama. Biomass and community structure were determined by analyzing the fatty acids of the extractable phospholipids. Activity was estimated by measuring the rate of enzymatic hydrolysis of fluorescein diacetate (FDA). In all four soils, biomass and activity declined with increasing depth; however, the magnitude and pattern of this decline varied as a function of soil type. Biomass concentrations in the lower Ap horizon ranged from 8.2 to 18.0 nmoles phospholipid/g dry wt soil. In the deepest subsoil horizons, the range was 0.0085 to 0.059 nmoles phospholipid/g dry wt soil. The rate of FDA hydrolysis was highly correlated with biomass (r = 0.90). Polyenoic fatty acids, which are present only in eukaryotic microorganisms, were found in all horizons; however, their relative abundance differed as a function of soil type. Stepwise regression analysis revealed that soil characteristics could explain 89 and 82% of the variation in biomass and activity, respectively. The results indicated that the vertical distribution of microorganisms in a soil profile differs greatly as a function of soil type. Hence, soil type may be an important determinant as to whether potentialmore » ground-water pollutants are biodegraded as they pass through the unsaturated zone of a soil profile.« less

Journal ArticleDOI
TL;DR: Experimental results show that this animal model of status epilepticus requires activation of muscarinic receptors because the initiation of seizures is blocked by atropine; requires presynaptic cholinergic activity because it is attenuated by hemicholinium-3; and recruits noncholinergic cells because when status epileptus is established it is not altered byatropine administration.

Journal ArticleDOI
TL;DR: Injection of carbachol into the brainstem of rats produced an increase in rapid eye movement (REM) sleep which was site- and dose-dependent and control experiments suggested that the drug-induced phenomenon appeared to be a increase in normal physiological REM sleep.

Journal ArticleDOI
TL;DR: The finding of acute microangiitis in a lung biopsy from a patient with pulmonary hemorrhage should suggest the diagnosis of SLE, and it may be a more reliable diagnostic feature than the demonstration of immune complexes.
Abstract: The authors describe four patients with systemic lupus erythematosus (SLE) and massive pulmonary hemorrhage in whom open-lung biopsies showed a distinctive small-vessel vasculitis. This lesion is characterized by acute inflammation and necrosis involving capillaries, arterioles, and small muscular arteries and is termed microangiitis to reflect the small size of the affected vessels. The involvement of capillaries is manifested by an infiltrate of necrotic neutrophils within alveolar septa often associated with destruction of the alveolar wall. This capillaritis was present in all cases, while involvement of arterioles and small arteries was seen in three. Immunofluorescence and electron microscopy demonstrated immune complexes in only two. The finding of acute microangiitis in a lung biopsy from a patient with pulmonary hemorrhage should suggest the diagnosis of SLE, and it may be a more reliable diagnostic feature than the demonstration of immune complexes.

Journal ArticleDOI
TL;DR: The results demonstrate a highly organized thalamic projection to the retrosplenial cortex of the rat.
Abstract: The topographic relationships between anterior thalamic neurons and their terminal projection fields in the retrosplenial cortex of the rat were characterized by experiments with the fluorescent dye retrograde labeling technique. The results demonstrate that the anterodorsal (DAD) and anteroventral (AV) nuclei project heavily to retrosplenial granular cortex (Rg) and to a lesser extent to retrosplenial agranular cortex (Rag). In contrast, the anteromedial (AM) and lateral dorsal (LD) nuclei project heavily to Rag and more lightly to Rg. Irrespective of terminal field in Rg or Rag, the neuronal cell bodies in AD and AV are organized topographically so that the neurons in the caudal part of each nucleus project to rostral retrosplenial cortex and the neurons in the rostral portion of each nucleus project to the caudal retrosplenial cortex. Further, the ventromedial AD and AV neurons project to rostral retrosplenial cortex, whereas dorsolateral neurons in both nuclei project to caudal retrosplenial cortex. LD neurons display a different topographic organization. The neurons in the medioventral part of LD project primarily to the rostral retrosplenial cortex, and the neurons in lateral LD project to the caudal retrosplenial cortex. This latter projection to the caudal retrosplenial cortex is also contributed to by neurons residing in the mediodorsal part of caudal LD. The neurons in AM that project to the retrosplenial cortex display less segregation than the AV, AD, or LD neurons. In all experiments, a number of neurons in the dorsal ventro-anterolateral nucleus were labeled by retrosplenial injections. The largest number of cells in this nucleus were labeled after Rag injections, and these were topographically organized such that the neurons projecting to the rostral Rag were located immediately deep to the internal medullary lamina, and the neurons projecting to the caudal Rag were more ventrally located. Very few thalamic neurons have axon collaterals to different areas of the retrosplenial cortex as shown by double labeling experiments. Together, these results demonstrate a highly organized thalamic projection to the retrosplenial cortex.

Journal ArticleDOI
TL;DR: The results obtained suggest that idiotype-directed interactions between neonatal B cells play an important role in the early establishment of the B cell repertoire which is subsequently expressed in adult mice.
Abstract: IgM hybridomas derived from perinatal B cells show a high degree of auto-reactivity and many had demonstrable anti-idiotypic reactivities by binding studies Selected multispecific antibodies were also shown to have potent idiotype-specific biological activities and if administered at appropriate stages of development could dramatically alter the responses of these mice when challenged with appropriate antigens in adult life The results obtained suggest that idiotype-directed interactions between neonatal B cells play an important role in the early establishment of the B cell repertoire which is subsequently expressed in adult mice

Journal ArticleDOI
TL;DR: In this paper, a representative sample (N = 241) of Alabama correctional officers responding to a survey instrument were subject to analysis, examining reported levels of burnout, stress and job satisfaction, findings were then compared to those from other studies.
Abstract: Perceptions and causes of burnout, job stress and job satisfaction among a representative sample (N = 241) of Alabama correctional officers responding to a survey instrument were subject to analysis. After examining reported levels of burnout, stress and job satisfaction, findings were then compared to those from other studies. Multiple regression procedures were then utilized to identify significant predictors. Results indicated that a number of potentially alterable, organizational factors had a significant impact on officer perceptions; accordingly, several intervention strategies are offered for consideration.

Journal ArticleDOI
01 Mar 1986-Pain
TL;DR: Results indicate that exercise quota systems produce systematic increases in both exercise levels and expectancies of capability while reducing worry and concern about exercising, and suggest that the effectiveness of Exercise quota systems is related to a deconditioning process based on exposure rather than the process of applying reinforcement to quota achievement.
Abstract: Reduced activity levels are a frequently encountered problem among chronic pain patients which has been shown to be responsive to exercise quota systems. This study extends the knowledge of exercise quota systems by examining their effects on beliefs relevant to exercise avoidance. Results indicate that exercise quota systems produce systematic increases in both exercise levels and expectancies of capability while reducing worry and concern about exercising. These data highlight the importance of avoidance learning in chronic pain and suggest that the effectiveness of exercise quota systems is related to a deconditioning process based on exposure rather than the process of applying reinforcement to quota achievement.

Journal ArticleDOI
TL;DR: High repetitive motions involving extreme wrist positions, especially flexion and ulnar deviation while grasping, are predominant in meat cutting and probably contribute to the development of carpal tunnel syndrome in this industry.
Abstract: A retrospective study was done to determine why a meat packing plant in Illinois had such an unusually high incidence of carpal tunnel syndrome In the past 12 years, 148% of employees at this plant have had a carpal tunnel release Only two of 117 patients remained unimproved at an average follow-up of 374 months The most consistent result after release was relief of the paroxysmal attacks of burning pain and paresthesia Weakness of grip was the most significant postoperative complaint in 78% Highly repetitive motions involving extreme wrist positions, especially flexion and ulnar deviation while grasping, are predominant in meat cutting and probably contribute to the development of carpal tunnel syndrome in this industry Previous reports of industrial carpal tunnel syndrome have not approached the incidence identified in this study Patient awareness and Workers' Compensation benefits may account for the high numbers seeking treatment

Book ChapterDOI
TL;DR: A significant body of experimental evidence supports the notion that a deficiency of either vitamin B12 or folic acid enhances the activity of various carcinogens, and unified mechanisms are proposed to explain this cocarcinogenic role.
Abstract: A significant body of experimental evidence supports the notion that a deficiency of either vitamin B12 or folic acid enhances the activity of various carcinogens. Unifying mechanisms are proposed to explain this cocarcinogenic role.

Journal ArticleDOI
TL;DR: This becomes a simple process with a graphics device having built-in B-spline generating capabilities such as the Evans and Sutherland PS300, and any irregularity in the ribbon is a strong visual cue, suggestive of potential problem areas during the refinement process.