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Biomedical subjects

H Grahn

Publications and source records attributed to H Grahn.

18 recordsLinked to original sources
PubMed1998

Diagnostic subgrouping of depressed patients by principal component analysis and visualized pattern recognition.

A data-analytical method is described for identifying behavioral and biological variables in psychiatric patients with predictive value in defining clinical subgroups. The procedure, based on principal component analysis (PCA) and graphical analysis, was applied in a group of 28 depressed patients. The 28 depressed patients of unipolar type were observed for up to 15 years for re-evaluation of the diagnoses at the start of the study. Platelet monoamine oxidase activity, post-dexamethasone serum cortisol and serum melatonin predicted two main clinical subgroups as well as a smaller subgroup of bipolar patients. The selection procedure revealed which of several variables were predictive of subgroups that were not possible to identify by univariate methods. The three biological variables may thus be useful in further assessment of clinical subgroups of unipolar depressed patients studied by other research groups.

Adult↗
PubMed1998

Affective disorder subtyped by psychomotor symptoms, monoamine oxidase, melatonin and cortisol: identification of patients with latent bipolar disorder.

A multivariate approach using pattern recognition method was applied on a multivariable data set from patients with affective disorders comprising biological and clinical variables. The depressed patients were rated according to 23 items of the comprehensive psychopathological rating scale (CPRS). Variables of importance were selected and clusters of patients were found by combining monoamine oxidase, melatonin and post-dexamethasone cortisol with symptoms of psychomotor retardation and agitation. Patients were distributed with high scores of agitation in the extreme of one direction and with high scores of retardation in the opposite direction. By using the combined clinical and biological variables, a diagnostic subcategory with latent bipolar disorder was identified. Two clusters of unipolar patients, one with low melatonin and low psychomotor retardation scores, and one with high melatonin and high psychomotor retardation scores, were found. Identification of a patient group with latent bipolar disorder may have potential therapeutic value since bipolar patients should be taken care of by a specialist in psychiatry, avoid tricyclic antidepressant therapy and may be candidates for lithium treatment.

Adult↗
PubMed1997

Endothelin-1 induced lesions of the frontoparietal cortex of the rat. A possible model of focal cortical ischemia.

Endothelin-1 (ET-1) was unilaterally applied onto the surface of the dorsal frontoparietal cortex of the rat. Cortical blood flow measurements using laser-Doppler flowmetry demonstrated dose-dependent reductions of frontoparietal cortical blood flow. Histological analysis demonstrated dose-related lesions and the time course was followed using MRI. The lesions appear to be associated with a large penumbra area indicated by morphological characteristics. Thus, cortical surface exposure to ET-1 may produce graded lesions of the frontoparietal cortex related to local ischemia.

Animals↗
PubMed1991

Multivariate data analysis of NMR data.

Multivariate methods based on principal components (PCA and PLS) have been used to reduce NMR spectral information, to predict NMR parameters of complicated structures, and to relate shift data sets to dependent descriptors of biological significance. Noise reduction and elimination of instrumental artifacts are easily performed on 2D NMR data. Configurational classification of triterpenes and shift predictions in disubstituted benzenes can be obtained using PCA and PLS analysis. Finally, the shift predictions of tripeptides from descriptors of amino acids open the possibility of automatic analysis of multidimensional data of complex structures.

Amino Acid Sequence↗
PubMed1989

Short time action of antirheumatic substances on the liver of rat. Protective effect of tryptophan + methionine.

1. A large number of drugs, including some antirheumatic substances, cause liver damage. 2. Only a little information is available, so far, on the causes of such damage and their prevention. 3. From studies on a number of antirheumatic drugs as to their effect upon the liver, three categories could be differentiated: (a) large effect (b) low effect (c) no effect. 4. Judging from our results, the liver damage is induced via a disturbance of the NAD-adenoribosylation metabolism.

Alanine Transaminase↗
PubMed1989

Toward a computer assisted analysis of NOESY spectra: a multivariate data analysis of an RNA NOESY spectrum.

A multivariate data-representation of a portion of the H-NOESY spectrum of an RNA octamer duplex was used to explore the possibility of using Principal Component Analysis and Partial Least Squares Discrimination for pattern recognition. In this case, it is found that the methods can: (i) distinguish slices containing signal from those containing only noise, (ii) locate slices containing overlapping signals, and (iii) in some cases to segregate slices with unique aspects such as those from terminal nucleotides, overlapping signals, purine-H8, pyrimidine-H6 and adenine-H2 containing slices. These properties can easily be included in a scheme to automate spectral analysis. The formulation described here does not distinguish patterns needed to automate sequential assignment of resonances in NOESY spectra of RNA.

Base Sequence↗
PubMed1987

Influence of oxypangam upon the induction of tyrosine aminotransferase, the NAD content and the ADPR transferase activity in several organs of the rat.

Oxypangam is a substance applied therapeutically against a number of diseases, such as chronic liver damages, angina pectoris, and psychosomatic disturbances. The mode of action of oxypangam has not yet conclusively been described. The only well-known properties of this substance are its intensive methylating and lipolytic effects. The present paper serves to elucidate the influence of oxypangam on the induction of the tyrosine aminotransferase, on the NAD content and on the activity of the ADPR transferase in the liver. Our studies showed that in normal animals, increasing doses of oxypangam support the induction of tyrosine aminotransferase. Up to a concentration of 100 mg/kg oxypangam enhances also the induction of tyrosine aminotransferase by tryptophan. In both cases, however, it does not work in adrenalectomized animals. Under the influence of oxypangam the NAD content of the liver remained unchanged, while the activity of the ADPR transferase was influenced only slightly.

Animals↗
PubMed1986

Influence of streptozotocin upon the induction of tyrosine aminotransferase, the content of NAD and of 5-methyl cytosine in rat liver.

The antibiotic, streptozotocin, has carcinostatic, carcinogenic, and diabetogenic properties. Moreover, it is capable of inducing the enzyme tyrosine aminotransferase in a permanent line of rat liver cells. In the present publication, the effects of streptozotocin upon the induction of tyrosine aminotransferase, NAD synthesis, and methylation of DNA in different organs were analyzed in vivo. If administered alone, streptozotocin slightly induced tyrosine aminotransferase. The induction of tyrosine aminotransferase caused by tryptophan or nicotinamide was inhibited by streptozotocin. Streptozotocin reduced the NAD content of the liver. NAD synthesis induced by tryptophan was reduced by streptozotocin, while that induced by nicotinamide was enhanced. DNA methylation in the form of 5-methyl cytosine was not influenced by streptozotocin.

5-Methylcytosine↗
PubMed1986

Influence of ethanol, nicotinamide, orotic acid and caffeine upon the induction of tyrosine aminotransferase, the NAD content and the ADPR transferase activity in rat liver.

Chronic uptake of ethanol leads to irreversible damage of liver cells. Until now the cause of this alteration is unknown. To get more information experiments presented in this paper were performed. Contrary to normal fed animals the enzyme tyrosine aminotransferase (TAT) can be induced by ethanol in starved rats. Orotic acid induces the TAT at a dose of 500 mg/kg. This effect is enhanced to some extent by ethanol. Ethanol increases the minor effect of 50 mg/kg caffeine on TAT induction markedly. Only 500 mg/kg nicotinamide (NA) enhances TAT activity. Here ethanol has a minor stimulatory effect. A combination of nicotinamide with orotic acid or with caffeine leads to substances with a higher effect on TAT induction. Besides nicotinamide and its derivatives only caffeine changes the NAD+ + NADH content of the liver. Ethanol and caffeine reduce the activity of the ADPR transferase. The results indicate that the effect of ethanol might be due to interference with NAD-adenoribosylation metabolism.

Adrenalectomy↗
PubMed1985

NAD metabolism and induction of tyrosine aminotransferase in the rat.

The relationship between the NAD-metabolism and the induction of the tyrosine aminotransferase was studied. The content of NAD+ + NADH differs markedly from organ to organ. The highest values can be found in the liver. In intact animals tryptophan leads to an increase of NAD in liver and kidney, but not in brain and spleen. Nicotinamide, on the other hand, induces NAD synthesis in all the organs tested. In adrenalectomized animals, however, there is practically no rise of the NAD content after application of tryptophan contrary to the effect of nicotinamide. The enzyme tyrosine aminotransferase can be induced in intact animals by nicotinamide and tryptophan. This effect is much less pronounced in adrenalectomized animals. In adrenalectomized animals the induction of the tyrosine aminotransferase by tryptophan is markedly elevated by caffeine and theophylline. Under these conditions there is a significant increase of the NAD content as well. The tryptophan promoted induction of the tyrosine aminotransferase is influenced by inhibitors of the ADPR-transferase. The data presented give further evidence that the NAD adenoribosylation metabolism is involved in the induction of the tyrosine aminotransferase.

Adrenalectomy↗
PubMed1985

Influence of ethanol upon the introduction of tyrosine aminotransferase in liver, upon the NAD content in liver and brain, and upon the activity of glutamate oxalate aminotransferase and glutamate pyruvate aminotransferase in the serum of rats.

The influence of ethanol, tryptophan, nicotinamide and methionine upon the activity of glutamate oxalate aminotransferase and glutamate pyruvate aminotransferase in serum as well as the induction of tyrosine aminotransferase in the liver, and of NAD+ + NADH in liver and brain are described. After oral application of 6 g/kg ethanol, the activities of the examined enzymes and the concentrations of NAD+ + NADH in the brain as well as in the liver did not change over a period of 8 hr. Administration of L-methionine lead--as is the case with DL-tryptophan--to a decrease of the NAD+ + NADH-concentration in the brain. A simultaneous application of nicotinamide, DL-tryptophan, L-methionine of l-methylnicotinamide together with ethanol caused a significant increase of the tyrosine aminotransferase induction in adrenalectomized animals. Ethanol reduced the activity of the ADPR transferase in the nuclei of rat liver cells.

Adrenalectomy↗
PubMed1984

Influence of azacytidine on the induction of tyrosine aminotransferase and the NAD metabolism in rat liver.

5-Azacytidine was found to inhibit the induction of tyrosine aminotransferase caused by L-tyrosine and hydrocortisone. The inhibitory effect can be overcome by L-methionine. There was only a slight inhibition of the tryptophan induction by 5-azacytidine in normal animals 4 hr after the administration of tryptophan. At 8 and 12 hr, a superinduction could be observed. The NAD content in adrenalectomized animals increased after application of tryptophan and 5-azacytidine. There was a slight inhibition of ADPR transferase in the rat liver.

Adrenalectomy↗
PubMed1983

Influence of N-methylformamide on the development, the NAD synthesis, and the activity of the ADPR transferase of rat embryos.

When N-methylformamide is administered to rats on the 11th day of pregnancy approximately 50% of the fetuses are resorbed and a reduced weight of the developed animals is found in comparison to the controls on the 21th day (delivery by Caesarian section). The toxic effect is increased by using nicotinamide and methionine. If a combination of these substances is employed practically all fetuses are resorbed. Tryptophan, however, has a considerably protective influence. N-Methylformamide has no influence on the NAD-synthesis induced by nicotinamide or tryptophan. It does, however, inhibits the activity of the ADPR transferase.

Animals↗
PubMed1983

Influence of dexamethasone phosphate upon the DNA- and the NAD-metabolism of concanavaline a stimulated T-lymphocytes.

1. Glucocorticoids have a decisive function in the immune system. In this paper, special attention is paid to the DNA and the NAD metabolism in T-lymphocytes of mice stimulated by Con A under the influence of dexamethasone phosphate. 2. Nicotinamide increases the incorporation of [3H]thymidine into the DNA of T-cells in dependence on the concentration. There is a similar but less pronounced effect with 1-methylnicotinamide. 3. Dexamethasone phosphate even at 10(-9) M inhibits the incorporation of [3H]thymidine into DNA. 4. The incorporation of [3H]thymidine into the DNA is reduced after preincubation of the T-cells with 6-aminonicotinamide or with 3-acetylpyridine. 5. Dexamethasone phosphate decreases the content of NAD in the T-cells. 6. The activity of the ADPR transferase increases after addition of Con A. Presence of nicotinamide stimulates the effect of Con A on this enzyme. This is not the case with 1-methylnicotinamide. The enzyme is inhibited drastically by dexamethasone phosphate. 7. It may be concluded that the NAD-adenoribosylation metabolism is markedly influenced by the mitogen Con A and by dexamethasone phosphate.

Animals↗
PubMed1983

5-methylcytosine content in different organs of the mouse and rat, several tumors and in mice embryos.

1. The content of 5-methylcytosine of the DNA of 11-day old mice embryos was compared with that of the DNA of different plasmocytoms. 2. Furthermore the DNA content was determined in different transplantable tumors and normal organs of the rat and the mouse. 3. By the aid of liquid chromatography significant differences could be demonstrated in the content of 5-methylcytosine of the DNA of BALB/c-mice or NMRI-mice and the DNA of the plasmocytom MOPC 104 E and MOPC 141, but not in the case of MOPC 321. 4. Clear differences could be observed with restriction enzymes: the DNA of all the plasmocytoms studied is more digested with Hpa II and Hha I than the DNA of the embryos. This is not the case however with MSP I. 5. The DNA of three transplantable tumors tested contains less 5-methylcytosine than the one of the liver kidney of the mouse and the rat. This was confirmed with restriction enzymes too.

5-Methylcytosine↗
PubMed1983

Influence of D-galactosamine upon the NAD-metabolism in rat liver.

After application of D-galactosamine a hepatitis develops in the rat liver. This can be prevented by different agents, including tryptophan. Yet it has not been possible to give definitive conclusions about the mechanism of galactosamine hepatitis. In this paper we report about the influence of galactosamine on the NAD metabolism. D-galactosamine inhibits the NAD synthesis initiated by nicotinamide in normal and adrenalectomized animals. The NAD synthesis from tryptophan is prevented in normal animals, in adrenalectomized ones however there is an increase of NAD in the presence of D-galactosamine reduces the activity of the ADPR transferase. Inhibitors of the ADPR transferase prevent the galactosamine hepatitis. From the results presented we conclude that the ADPR transferase plays an important role in the development of the galactosamine hepatitis.

Adrenalectomy↗
PubMed1982

Influence of DL-ethionine on the NAD content and on the activity of the poly(ADPR)synthetase in the rat liver.

1. Ethionine, an analogue of methionine, is known to cause a number of serious changes. In this study, its influence on the NAD + NADH2 content and on the activity of the poly(ADPR)synthetase in rat liver has been investigated. 2. DL-Ethionine decreases the content of NAD + NADH2 in adrenalectomized, but not in normal animals. 3. After injection of nicotinamide the NAD + NADH2 content in the liver of adrenalectomized rats is much higher than in that of normal ones. 4. DL-Ethionine diminishes the NAD synthesis caused by nicotinamide in adrenalectomized animals and increases it in normal ones. DL-Tryptophan induces only a slight NAD synthesis, which is reduced in adrenalectomized animals by thionine. 5. 1-Methylnicotinamide slightly decreases the NAD concentration in normal animals, but increases it considerably in adrenalectomized ones. DL-ethionine reduces the NAD + NADH content in adrenalectomized animals in the presence of 1-methylnicotinamide. 6. The activity of poly(ADPR)synthetase of in-vitro tested nuclei is slightly increased after treatment with DL-ethionine.

Adrenalectomy↗