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Biomedical subjects

K Frederiksen

Publications and source records attributed to K Frederiksen.

At least 19 recordsLinked to original sources

Do risk factors for epithelial ovarian cancer have an impact on prognosis? Focus on previous pelvic surgery and reproductive variables.

OBJECTIVES: The prognostic impact of risk factors for ovarian cancer development is sparsely explored, but previous sterilisation has been shown to have a negative impact on survival. METHODS: Ovarian cancer cases were from the Danish MALOVA study. Information on previous pelvic surgery as well as reproductive variables was obtained from a personal interview conducted closely after primary surgery. Cox regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for ovarian cancer specific death in relation to previous pelvic surgery and reproductive variables including lifetime number of ovulation years. RESULTS: A total of 295 women with Stage III ovarian carcinomas were identified and followed to death or for a median of 7.3 years (range 5.4-9.5 years). Previously sterilised or hysterectomised women seemed to have a slightly decreased risk of ovarian cancer death (HR = 0.62; 95% CI: 0.36-1.08 and HR = 0.82; 95% CI: 0.55-1.21), although none of these associations reached statistical significance. The prognostic impacts of the individual reproductive variables followed the same pattern as the impact of the variables on ovarian cancer development, although significance was only reached for age at menarche (HR = 0.91 per year; 95% CI: 0.84-0.99). By accumulation of the possible minor effects of the reproductive variables in calculation of the total lifetime number of ovulation years, we found that survival decreased significantly with increasing number of ovulations (HR = 1.53 per 10 years; 95% CI: 1.09-2.14). CONCLUSION: Increasing lifetime number of ovulations was a negative prognostic factor for ovarian cancer specific survival. Previous sterilisation or hysterectomy seemed to be associated with improved survival.

Adenocarcinoma↗

Atypical cancer pattern in patients with Parkinson's disease.

Among 14,088 patients, with a primary diagnosis of Parkinson's disease during the period 1977-98 identified from the National Register of Patients, 1282 cancers were subsequently recorded in the Danish Cancer Registry, compared with 1464 expected, with a standardised incidence ratio (SIR) of 0.88 (95% confidence interval (CI), 0.8-0.9). Significantly reduced risks were found for smoking-related cancers, for example, cancers of the lung (SIR, 0.38), larynx (0.47) and urinary bladder (0.52), although moderate reductions in risk were also seen for several nonsmoking-related cancers. In contrast, increased risks were seen for malignant melanoma (SIR, 1.95; 95% CI, 1.4-2.6), nonmelanocytic skin cancer (1.25; 1.1-1.4) and breast cancer (1.24; 1.0-1.5). The observed cancer pattern supports the hypothesis that constituents of tobacco smoke inhibit or delay the development of Parkinson's disease, but a low smoking prevalence appears to be only part of the explanation for the decreased cancer incidence. The increased relative risks of melanoma and nonmelanoma skin cancer are not likely to be artefactual, but further investigations of potential mechanisms are warranted.

Aged↗

Waist circumference and body composition in relation to all-cause mortality in middle-aged men and women.

OBJECTIVE: Waist circumference is directly related to all-cause mortality when adjusted for body mass index (BMI). Body fat and fat-free body mass, when mutually adjusted, show with increasing values an increasing and decreasing relation to all-cause mortality. We investigated the association of waist circumference and body composition (body fat and fat-free mass), mutually adjusted, to all-cause mortality. DESIGN: A Danish prospective cohort study with a median follow-up period of 5.8 y. SUBJECTS: In all, 27 178 men and 29 875 women, born in Denmark, aged 50-64 y, and without diagnosis of cancer at the time of invitation. MEASUREMENTS: Waist circumference and body composition estimated from impedance measurements. Cox's regression models were used to estimate the mortality rate ratios (RR). RESULTS: Waist circumference was strongly associated with all-cause mortality after adjustment for body composition; the mortality RR was 1.36 (95% confidence intervals (CI): 1.22-1.52) times higher per 10% larger waist circumference among men and 1.30 (95% CI: 1.17-1.44) times higher among women. Adjustment for waist circumference eliminated the association between high values of the body fat mass index (BFMI) and all-cause mortality. The association between fat-free mass index (FFMI) and mortality remained unaltered. CONCLUSION: Waist circumference accounted for the mortality risk associated with excess body fat and not fat-free mass. Waist circumference remained strongly and directly associated with all-cause mortality when adjusted for total body fat in middle-aged men and women, suggesting that the increased mortality risk related to excess body fat is mainly due to abdominal adiposity.

Abdomen↗

Waist and hip circumferences and all-cause mortality: usefulness of the waist-to-hip ratio?

OBJECTIVE: To investigate whether waist and hip circumferences, in addition to body mass index (BMI), are related to all-cause mortality. We studied these associations and tested the usefulness of the waist-to-hip ratio for mortality prediction. DESIGN: A Danish prospective cohort study with data collected between 1993 and 1997. SUBJECTS: A total of 27 179 men and 29 875 women born in Denmark and aged 50-64 years were followed for a median of 6.8 years. MEASUREMENTS: BMI, waist and hip circumferences at baseline. RESULTS: The associations between hip circumference and all-cause mortality were inverse for both men and women, but only after adjustment for waist circumference, or BMI, or both. The mortality rate ratios of mutually adjusted waist and hip circumferences were 0.63 (95% CI: 0.56, 0.71), and 0.70 (95% CI: 0.63, 0.79) times higher per 10% larger hip circumference in men and women, respectively, and 1.45 (95% CI: 1.34, 1.57) and 1.22 (95% CI: 1.14, 1.31) times higher per 10% larger waist circumference. The adequacy of the waist-to-hip ratio as a substitute for separate measurements of waist and hip circumferences depended on which other variables the analysis was adjusted for, indicating that the waist-to-hip ratio should be used with precaution. CONCLUSION: When mutually adjusted, waist and hip circumferences show opposite associations with all-cause mortality, probably due to different effects of adipose tissue in the abdominal and gluteofemoral regions. The waist-to-hip ratio cannot always capture these relations adequately.

Body Constitution↗

Immortalized neural cells from trisomy 16 mice as models for Alzheimer's disease.

The trisomy 16 mouse (Ts16) is a general accepted animal model for both Downs syndrome (DS) and Alzheimer's Disease (AD). However, the efficacy of this model is severely hampered by the fact that Ts16 is lethal after about 18-20 days of gestation. Chimeras, long-term tissue culture and neural transplantation of Ts16 material have previously been used to overcome this limitation presented by death in utero of the Ts16. In this paper we describe a new strategy to overcome this limitation, i.e. immortalization of primary cells from Ts16 mice with retrovirus-mediated gene transfer of a temperature sensitive immortalizing oncogene. By this method we have obtained a total of 21 stable cell lines from Ts16 hippocampus, Ts16 cortex, normal hippocampus, and normal cortex. So far, two of the cell lines have been karyotyped and as expected, the cell line immortalized from Ts16 embryos has retained three copies of chromosome 16. We are currently characterizing these cell lines with respect to expression of APP, T-antigen, Nestin, GFAP, NF and Map-2. Moreover, the processing and secretion of APP fragments are being investigated by immunoblotting. In summary, we have immortalized CNS cells from Ts16 mice and we expect that these cell lines will be useful as in vitro and in vivo models for studying various aspects of the pathology of Alzheimer's disease.

Alzheimer Disease↗

Minimum Data Set Plus (MDS+) scores compared with scores from five rating scales.

OBJECTIVE: To compare mandated Minimum Data Set Plus (MDS+) ratings of behavior, function, mood, communication, and cognition to ratings of these domains using analogous research instruments. DESIGN: Cross-sectional correlational study of criterion-related validity. SETTING: Three nursing homes in Rochester, New York. PARTICIPANTS: Fifty-two nursing home residents. MEASUREMENTS: Nursing home staff completed the MDS+ for each subject. Research scales were completed by trained research clinicians, independently of and blinded to the MDS+ results, using the Mini-Mental State Exam (MMSE), Brief Psychiatric Rating Scale (BPRS), Dementia Mood Assessment Scale (DMAS), Psychogeriatric Dependency Rating Scale (PGDRS), and Physical Signs and Symptoms Scale (PSMS). RESULTS: MDS+ measures of functional status, cognitive impairment, and communication were highly correlated with comparable research rating scale scores. Pearson correlation between MDS-functional status and PSMS scores was 0.89, between MDS-dementia and BPRS Factor 3 (representing cognitive dysfunction) and MMSE scores was 0.85 and 0.77, respectively, and between MDS-communication and MMSE and PGDRS Item 6 (assessing communication) scores was 0.74 and 0.62, respectively. Behavior and mood scores did not correlate nearly as well with comparable research scale scores. Pearson correlation between MDS- behavior and PGDRS and BPRS total scores was 0.54 and 0.51, respectively , and between MDS-mood and BPRS Factor 1 (depression) and DMAS 1-17 subtotal (mood disturbance) scores was 0.20 and 0.20, respectively. CONCLUSION: This preliminary study in a small sample shows marked agreement between three of the five MDS+ components analyzed and comparable research rating scales and confirms that behavior and mood are difficult to assess with simple instruments.

Activities of Daily Living↗

Enhanced D1 affinity in a series of piperazine ring substituted 1-piperazino-3-arylindans with potential atypical antipsychotic activity.

A study of the effect of aromatic substitution on D1 and D2 affinity in a series of previously reported trans-1-piperazino-3-phenylindans shows similar structure-activity relationships for the two receptor sites. 6-Substituted derivatives have affinity for both receptors, and 6-chloro-or 6-fluoro-substituted derivatives show preference for D1 receptors. D1 affinity and selectivity are significantly increased in a series of new piperazine ring substituted derivatives. Potent D1 and D2 antagonism in vivo are confined to derivatives with relatively small substituents in the 2-position of the piperazine ring (e.g. 2-methyl,2,2-dimethyl, 2-spirocyclobutyl or 2-spirocyclopentyl). Consequently, the effect of aromatic substitution is examined in a series of 1-(2,2-dimethylpiperazino)-3-arylindans. All these compounds except the 4-, 5-, 7- and 4'-chloro-substituted derivatives have potent D1 affinity (IC50's below 10 nM) and the majority of the compounds antagonize SK&F 38393-induced circling in 6-OHDA-lesioned rats with ED50 values about 1 mumol/kg. In vitro all compounds show preference for D1 receptors, but in vivo they are equally effective as D1 and D2 antagonists. The compounds have high affinity for 5-HT2 receptors and selected compounds show high affinity for alpha 1 adrenoceptors. Furthermore, a subgroup consisting of (-)-38, (-)-39, (-)-41, and (-)-54 does not induce catalepsy in rats. These compounds have the potential of being "atypical" antipsychotics and have consequently been selected for further studies. The non-receptor-blocking enantiomers are shown to be inhibitors of DA and NE uptake in accordance with previous observations in compounds unsubstituted in the piperazine ring. Two compounds, (+)-38 and (+)-40, block DA uptake with IC50 values below 10 nM. Finally, the observed structure-activity relationships are discussed in relation to previously published pharmacophore models for D2 and 5-HT2 receptors. It is concluded that the piperazine substituents might induce a different binding mode at the dopamine receptor sites, perhaps only at the D1 receptor site.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Lack of carbamazepine toxicity in frail nursing home patients: a controlled study.

OBJECTIVE: To assess the effects of carbamazepine and placebo on measures of toxicity in frail nursing home patients. DESIGN: A nonrandomized, double-blind, placebo-controlled crossover study. SETTING: Two nursing homes in Rochester, New York. PARTICIPANTS: Twenty-five subjects (mean age 84.5 years) with dementia. INTERVENTION: Carbamazepine and placebo during two 5-week periods separated by a 2-week washout. The modal dose for each patient was 300 mg/day. MEASUREMENTS: Adverse experiences, comorbid events, and physical signs and symptoms were assessed continuously, and laboratory data were examined at the beginning and end of each treatment period. RESULTS: One subject died with a pneumonia (and elevated white blood cell count), and one subject developed probable carbamazepine-induced tics. There was a minimal drop in hematocrit and a slight elevation of liver enzymes, none of which was clinically significant. There was otherwise no excess of adversity or comorbid events on carbamazepine versus placebo, and there was no change in electrolytes or other laboratory measures. CONCLUSION: The findings indicate that carbamazepine in this dose range was well tolerated for the 5-week treatment period in this frail sample. These data supplement the literature regarding carbamazepine toxicity, which is devoid of controlled studies in older subjects.

Aged↗

Bioisosteres of arecoline: 1,2,3,6-tetrahydro-5-pyridyl-substituted and 3-piperidyl-substituted derivatives of tetrazoles and 1,2,3-triazoles. Synthesis and muscarinic activity.

A series of arecoline bioisosteres, where the ester group is replaced by a 1,2,3-triazole-4-yl or a tetrazole-5-yl group, was synthesized and evaluated in vitro for affinity and efficacy at muscarinic receptors and in vivo for cholinergic side effects. The corresponding piperidine derivatives were also studied. In the 1,2,3,6-tetrahydropyridyl-1,2,3-triazole series, only derivatives with 2-substituents in the 1,2,3-triazole ring exert muscarinic agonist activity. The same trend is seen in the corresponding tetrazole series, where only 2-substituted derivatives display muscarinic agonist activity. The methyl derivatives in both series are full agonists, whereas the derivatives with longer side chains are partial agonists. Introduction of methyl substituents in the 1,2,3,6-tetrahydropyridine ring generally lowers affinity considerably except for the 3-substituted derivatives, where some activity is retained. In both the 1,2,3-triazole and tetrazole series, derivatives without substituents at the basic nitrogen in the 1,2,3,6-tetrahydropyridine ring are unselective full agonists, whereas the methyl-substituted derivatives generally are more M1 selective compared to M2. Larger substituents than methyl abolish activity. The 4-(3-piperidyl)-1,2,3-triazole and 5-(3-piperidyl)-2H-tetrazole derivatives are generally less active than the corresponding 1,2,3,6-tetrahydropyridine derivatives, and only the 2-allyl- and 2-propargyl-1,2,3-triazole derivatives display activities comparable to the most active compounds in the 1,2,3,6-tetrahydropyridine series. The propargyl derivative is an unselective full agonist, and resolution did not reveal any stereoselectivity The allyl derivative is a partial agonist with some selectivity for the M1 receptor, and testing of the enantiomers showed that the (+)-enantiomer is an unselective partial agonist, whereas the (-)-enantiomer is a partial agonist with preference for the M1 receptor. Generally, the structure-activity relationships of the 1,2,3-triazole and tetrazole series are very similar, and two compounds, 2-ethyl-4-(1-methyl-1,2,3,6-tetrahydro-5-pyridyl)-1,2,3-triazole and 2-ethyl-5-(1-methyl-1,2,3,6-tetrahydro-5-pyridyl)-2H-tetrazole, are M1 agonists/M2 antagonists. Muscarinic compounds with this profile are of particular interest as drugs for the treatment of Alzheimer's disease.

Animals↗

Resolution, absolute stereochemistry, and pharmacology of the S-(+)- and R-(-)-isomers of the apparent partial AMPA receptor agonist (R,S)-2-amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid [(R,S)-APPA].

(R,S)-2-Amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid ((R,S)-APPA) is the only partial agonist at the (R,S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) subtype of excitatory amino acid receptors so far described. In light of the pharmacological interest in partial agonists, we have now accomplished the resolution of (R,S)-APPA. (S)-(+)-APPA (5) and (R)-(-)-APPA (6) were obtained in high enantiomeric purity using (R)-(+)- and (S)-(-)-1-phenylethylamine, respectively, as resolving agents. The absolute stereochemistry of 6 was established by X-ray analysis of 6.HCl.0.25H2O. Compounds 5 and 6 were tested electropharmacologically using the rat cortical wedge preparation and in receptor-binding assays using [3H]-AMPA, [3H]kainic acid, and the N-methyl-D-aspartic acid (NMDA) receptor ligands [3H]CPP, [3H]MK-801, and [3H]glycine. Whereas 6 did not significantly affect the binding of any of these ligands (IC50 > 100 microM), compound 5 revealed affinity for only the [3H]AMPA-binding site (IC50 = 6 microM). In electropharmacological tests, 5 showed full AMPA receptor agonism (EC50 = 230 microM). This effect of 5 was insensitive to the NMDA antagonist CPP but was inhibited competitively by the non-NMDA antagonist NBQX (pKi = 6.30). Compound 6, on the other hand, turned out to be a non-NMDA receptor antagonist, inhibiting competitively depolarizations induced by AMPA (pKi = 3.54), kainic acid (pKi = 3.07), and 5 (pKi = 3.57).

Alanine↗

NNC-711, a novel potent and selective gamma-aminobutyric acid uptake inhibitor: pharmacological characterization.

NNC-711 (1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1,2,5,6-tetrahydro-3- pyridinecarboxylic acid hydrochloride) is a novel, potent and selective gamma-aminobutyric acid (GABA) uptake inhibitor. NNC-711 inhibited synaptosomal (IC50 = 47 nM), neuronal (IC50 = 1238 nM) and glial (IC50 = 636 nM) GABA uptake in vitro NNC-711 lacked affinity for other neurotransmitter receptor binding sites, uptake sites and ion channels examined in vitro. In vivo, NNC-711 was a potent anticonvulsant compound against rodent seizures induced by methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) (ED50 (clonic) = 1.2 mg/kg i.p.), pentylenetetrazole (PTZ) (ED50 (tonic) = 0.72 mg/kg i.p., mouse; and ED50 (tonic) = 1.7 mg/kg, rat), or audiogenic (ED50 (clonic and tonic) = 0.23 mg/kg i.p.). At higher doses NNC-711 produced behavioral side effects characterized by inhibition of traction (ED50 = 23 mg/kg i.p.), rotarod (ED50 = 10 mg/kg i.p.) and exploratory locomotor activity (ED50 = 45 mg/kg i.p.) in the mouse. Following acute (3-h) in vivo pretreatment with NNC-711, behavioral tolerance developed to its motor impairing side effects (inhibition of traction, rotarod or exploratory locomotor activity) without corresponding tolerance to the anticonvulsant effects. These data suggest that NNC-711 will be useful for future in vitro and in vivo experiments to elucidate the role of the GABA uptake carrier in the central nervous system.

Animals↗

CA-125, placental alkaline phosphatase and tissue polypeptide antigen as preoperative serum markers in ovarian carcinoma.

Blood samples were drawn before laparotomy in 42 cases of benign, 17 cases of borderline, and 53 cases of malignant epithelial ovarian neoplasms. The concentrations of CA-125, tissue polypeptide antigen, and placental alkaline phosphatase (PLAP) were determined. No significant difference was found between the levels of CA-125 and TPA. No significant correlation was seen between tumour type and these two markers; however, both were significantly correlated to tumour malignancy and clinical stage, and CA-125 was also correlated to tumour grade. No correlation was found between PLAP and the other markers or any of the above-mentioned parameters. If at least one of two or three markers was requested to be positive, a moderate increase in the 'detection rate' of malignant tumours was found. However, the rate of positive benign samples increased to as much as 41%. Requesting at least two markers out of two or three to be positive certainly reduced the number of 'false-positive' benign tumours, but the sensitivity for malignant tumours was reduced concomitantly to levels where marker determinations would be of little use. The study demonstrated a possible, but limited role for preoperative determinations of the markers. A combination of two or three markers was not superior to single markers. The results indicate that neither of these markers will be of significant value in a screening context.

Adenocarcinoma, Mucinous↗

A paper membrane filter assay for ciliate chemoattraction.

A quantitative bioassay for ciliate chemoattraction based on the Boyden assay is described with the ciliates Tetrahymena thermophila and Tetrahymena pyriformis as test organisms. A chamber is separated into two compartments by a Whatman 3MM filter, and a suspension of starved cells (approximately 10(5) cells/ml) is placed in one compartment and a solution containing attractant in the other. The gradient of chemoattractant across the filter causes the cells to swim through the filter into the attractant-containing compartment where their appearance is determined by electronic cell counting. The assay described is convenient with a signal-to-noise ratio of approximately 10. It is shown here to work with the attractants proteose peptone and platelet-derived growth factor.

Animals↗

(R)-N-[4,4-bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid binds with high affinity to the brain gamma-aminobutyric acid uptake carrier.

(R)-N-[4,4-Bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid (NO 328) has previously been shown to be a potent anticonvulsant in both mice and rats. Here, we report that NO 328 is a potent inhibitor of gamma-[3H]aminobutyric acid [( 3H]GABA) uptake in a rat forebrain synaptosomal preparation (IC50 = 67 nM) and in primary cultures of neurons and astrocytes. Inhibition of [3H]GABA uptake by NO 328 is apparently of a mixed type when NO 328 is preincubated before [3H]GABA uptake; the inhibition is apparently competitive without preincubation. NO 328 itself is not a substrate for the GABA uptake carrier, but NO 328 is a selective inhibitor of [3H]GABA uptake. Binding to benzodiazepine receptors, histamine H1 receptors, and 5-hydroxytryptamine1A receptors was inhibited by NO 328 at 5-30 microM, whereas several other receptors and uptake sites were unaffected. [3H]NO 328 showed saturable and reversible binding to rat brain membranes in the presence of NaCl. The specific binding of [3H]NO 328 was inhibited by known inhibitors of [3H]GABA uptake; GABA and the cyclic amino acid GABA uptake inhibitors were, however, less potent than expected. This indicates that the binding site is not identical to, but rather overlapping with, the GABA recognition site of the uptake carrier. The affinity constant for binding of [3H]NO 328 is 18 nM, and the Bmax is 669 pmol/g of original rat forebrain tissue. The regional distribution of NaCl-dependent [3H]NO 328 binding followed that of synaptosomal [3H]GABA uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Modelling excess mortality of the unemployed: choice of scale and extra-Poisson variability.

"Occupational mortality and morbidity is usually studied via standardized mortality (or morbidity) ratios, with little attention to the basic fit of the implicit underlying proportional hazards model. This paper presents a case study on unemployment and mortality, based on the complete Danish male population aged 20-64 years at the 1970 census. The effect of unemployment on the age-specific mortality rate is intermediate between additive and multiplicative and was fitted well by an additive effect on the square root of the mortality. The paper discusses and illustrates whether finer stratification or random residual variation ('frailty') is to be preferred for obtaining a statistically satisfactory fit."

Demography↗

Prevalence of and mortality from human immunodeficiency virus type 2 in Bissau, West Africa.

In a community based prevalence study of HIV infection in Bissau, West Africa, 1987, the population in 100 randomly selected "houses" was asked to participate. 89% (1329/1499) were examined and had a blood sample taken. None was HIV-1 seropositive but 4.7% were seropositive for HIV-2 (0.6% in children, 8.9% in those aged 15 years and over, and 20% in those aged 40 years and over). There was no significant difference in seroprevalence between areas or ethnic groups or between individuals of different civil status when age was taken into account. Sexual contact and blood transfusions were the dominant transmission routes, and no case of vertical transmission was identified. The HIV-2 seroprevalence in spouses of HIV-2 seropositive index persons was 40%. For a history of blood transfusion the relative risk of being HIV-2 seropositive was 103.6 in children and 2.4 for adults. After exclusion of spouses, no clustering of HIV-2 seropositivity was seen. At follow-up, after a mean observation time of 325 days, there was an excess mortality for HIV-2 seropositives. The relative risk of dying for HIV-2 seropositive children was 60.8 and for adults 5.0.

Adolescent↗

Immortalization of precursor cells from the mammalian CNS.

Recent studies show that the nervous system contains many molecularly distinct cell types. Clonal cell marking experiments demonstrate that different cell types in some areas of the CNS are products of a multipotential stem cell. The factors controlling the differentiation of vertebrate CNS precursor cells would be more accessible to molecular analysis if cell lines with precursor properties could be established. Here we show that cell lines expressing an antigenic marker specific for a major brain precursor cell population can be established from rat cerebellum. We demonstrate that cell lines express the precursor, neuronal or glial properties depending on the growth conditions. This work supports the view that brain precursor cells expressing the marker Rat 401 are multipotential and can differentiate into cells with either neuronal or glial properties. Cell lines capable of differentiation should be useful in defining the signaling systems generating the cell types of the brain.

Animals↗