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Biomedical subjects

R Kauppinen

Publications and source records attributed to R Kauppinen.

At least 55 records · Page 3Linked to original sources
PubMed1993

Elevated seizure threshold and impaired spatial learning in transgenic mice with putrescine overproduction in the brain.

We have studied the role of putrescine by using transgenic mouse lines overexpressing the human ornithine decarboxylase gene in most of their tissues. The aberrant expression of the transgene is most strikingly manifested in the brain, leading to an increase of up to 20-fold in putrescine content. We report that the transgenic mice with grossly elevated putrescine in all brain regions analysed (cortex, striatum, hippocampus and cerebellum) showed a significantly elevated seizure threshold to chemical and electrical stimuli, and impaired performance in spatial learning and memory tests. The view that putrescine may be primarily responsible for these changes was supported by the fact that the concentrations of the major neurotransmitter amino acids, glutamate and GABA in the brain, were not changed in the transgenic animals, and by the finding that a further increase in brain putrescine, achieved by inhibition of the catabolism of L-ornithine, appeared to provide additional protection against electroshock-induced seizures. These results suggest that the commonly observed increase in ornithine decarboxylase activity and the massive increase in brain putrescine in connection with neuron damage is a neuroprotective measure rather than a cause of the damage.

Animals↗
PubMed1993

Nuclear magnetic resonance spectroscopy of plasma to distinguish between malignant and benign diseases causing jaundice and cholestasis.

The sera of 51 patients with malignant (n = 25) and benign (n = 26) hepatopancreatobiliary disorders were analysed by 1H magnetic resonance spectroscopy (NMR) in order to distinguish between malignant and benign diseases causing jaundice and/or cholestasis. Macromolecular linewidths were determined both manually and automatically with a computed analysis, and both methylene (CH2) and methyl (CH3) resonances were evaluated. The mean linewidth of the CH3 peak was significantly narrower in the patients with malignant disease than in the patients with benign disease both in the manual and computed analyses, but no significant differences in the CH2 peak were detected. Diagnostic sensitivity and specificity of the CH3 peak determined in the computed analysis were 92% and 27% respectively. In the light of the current study, it seems obvious that because overlap between benign and malignant groups was too great, 1H NMR spectroscopy of plasma is not of practical value in distinguishing between benign and malignant causes of jaundice and/or cholestasis.

Adolescent↗
PubMed1993

Hemi-Kock reconstruction following cystectomy: experience and results from a small urological unit.

Between December 1988 and January 1992, 11 men underwent lower urinary tract reconstruction by means of the hemi-Kock ileal reservoir following radical cystoprostatectomy (ten patients) and subtotal cystectomy (one patient). Six of the 11 patients developed an early postoperative complication, with a fatal outcome in two of them. One patient succumbed to subarachnoidal bleeding and one to septic shock. During the follow-up, another two men died of advanced bladder carcinoma. The late complication rate was low. Most patients regained their continence within six months. A good continence was achieved in all the nine remaining patients during the day and in six of them at night. This experience suggests that the hemi-Kock reservoir is a useful method for the urinary tract reconstruction following cystectomy.

Cystectomy↗
PubMed1992

CRIM-positive mutations of acute intermittent porphyria in Finland.

Acute intermittent porphyria (AIP) is a dominantly inherited metabolic disease caused by a partial deficiency of the third enzyme, porphobilinogen deaminase (PBGD), in the heme biosynthetic pathway. AIP has been divided into two subtypes according to the ratio of enzyme polypeptide concentration and enzyme activity measured in erythrocytes: cross-reacting immunologic material (CRIM) positive or negative. In this study six out of the seven known CRIM-positive AIP families in Finland were analyzed and two also previously identified mutations in the PBGD gene were found to be responsible for AIP in this genetically isolated population. The search for mutations was focused on exon 10 based on previously found mutations. SSCP analysis revealed a known polymorphism but the two mutations in that region were found only by direct sequencing of the PCR products. A G518-->A substitution changing Arg173 to Gln was found in three families and a C499-->T substitution changing Arg167 to Trp was detected in three families. DNA analyses of the family members revealed that conventional assays of erythrocyte PBGD activity identified correctly only 72% of the carriers for the AIP mutation.

Amino Acid Sequence↗
PubMed1992

Single-strand conformation polymorphism (SSCP) analysis applied to the diagnosis of acute intermittent porphyria.

The single-strand conformation polymorphism (SSCP) technique was used to detect carriers of the known point mutation in the first exon of the porphobilinogen deaminase gene in Finnish and Swedish families. The SSCP technique was a reliable and convenient way of distinguishing patients from healthy members in a family. This point mutation is thought to result from a splicing defect of the mRNA. The PCR-based analyses of a patient's cDNA did not reveal the presence of an abnormal mRNA population, suggesting that no abnormal mRNA is synthesized or that it is too unstable to be detected.

Base Sequence↗
PubMed1992

Frequency of low erythrocyte porphobilinogen deaminase activity in Finland.

The frequency of low erythrocyte porphobilinogen deaminase (PBGD) activity was investigated in 2234 blood donors and in 30 patients with acute intermittent porphyria. The mean enzyme activities (+/- SD) were 3.38 +/- 0.58 U and 1.82 +/- 0.41 U, respectively. Eighteen blood donors without any history of symptoms of porphyria or haematological disease had low PBGD activity (less than 2.20 U), and they were studied further. All of them also had subnormal concentrations of the erythrocyte enzyme protein, as determined by an immunological method. Lymphocyte PBGD activity was within the normal range, but this parameter does exhibit a wide overlap between normal and porphyric values. Urinary excretion of porphobilinogen was moderately increased in two of the blood donors. In four of the 18 families of the blood donors with low PBGD activity several first-degree relatives had low erythrocyte enzyme activity, consistent with a dominant mode of inheritance. The 5-aminolaevulinic acid loading-test was normal in the blood donors with familial occurrence of low erythrocyte PBGD. It is concluded that inherited defects in erythrocyte PBGD occurred among Finnish blood donors with a frequency of about 1 in 500. The defects may be identical with those in acute intermittent porphyria (AIP), but other mechanisms are also possible, e.g. a mutation in the erythroid-specific part of the PBGD gene.

Adult↗
PubMed1992

Prognosis of acute porphyria: occurrence of acute attacks, precipitating factors, and associated diseases.

We evaluated the prognosis of acute porphyria among 206 adult Finnish patients with acute intermittent porphyria (AIP) or variegate porphyria (VP). The series represents all known patients with these porphyrias in Finland. Of the 47 patients who had a total of 117 acute attacks during the period 1967-1989, 6 died during an attack and 21 attacks were associated with paresis; the frequency of severe attacks was significantly smaller than before 1967 (p = 0.00002). Most pareses and deaths occurred because of a delay in diagnosis and inappropriate treatment of porphyria. For those patients who were symptom-free at the time of diagnosis (1365 follow-up years), the risk of the first subsequent attack was significantly smaller than for those who had had an acute attack before the diagnosis of porphyria (1047 follow-up years, p = 0.005). In addition, milder symptoms of porphyria were more common among those who had had previous attacks than among those who had not (p less than 0.00001). In AIP the risk of attacks correlated with the excretion of porphobilinogen in the urine during remission among adults (p = 0.03); a low rate of excretion predicted freedom from acute attacks. A regular use of many precipitating drugs was never associated with symptoms of porphyria. Two percent of the surgical operations and 4% of the pregnancies were associated with acute attacks. Nearly one-third of the women had symptoms of porphyria associated with the menstrual cycle, but these seldom proceeded to an acute attack. Forty-six percent of the women had used sex-hormone preparations regularly; 2 of them (4.5%) experienced associated acute attacks. Patients with AIP or VP showed increased incidences of hepatocellular carcinoma, and probably also chronic renal failure and hypertension.

Acute Disease↗
PubMed1990

RFLP analysis of three different types of acute intermittent porphyria.

Restriction fragment length polymorphism (RFLP) analysis was performed in three Finnish families with different subtypes of acute intermittent porphyria (AIP): 1) cross-reacting immunological material (CRIM)-negative with low erythrocyte porphobilinogen (PBG)-deaminase activity, 2) CRIM-positive with low PBG-deaminase activity and 3) CRIM-negative with normal PBG-deaminase activity. The disease-associated RFLP haplotype (A2B1C2) of the PBG-deaminase gene was the same in each family. In all three families, RFLP linkage analysis resulted in highly positive lod scores. The maximal lod score (4.3) was obtained at the recombinant fraction of zero, thus confirming a tight linkage of AIP to the PBG-deaminase locus. Of the 62 family members tested, 30 had the disease-associated haplotype; in 5 of them, conventional tests for AIP were normal and in one, uncertain. RFLP analysis can thus reveal new gene carriers and help in the diagnosis of individuals with uncertain results in other laboratory tests.

Acute Disease↗
PubMed1989

Histidine release from brain slices and synaptosomes.

The release of radioactive histidine was studied in a superfusion system by using preloaded rat cerebral cortical slices and guinea pig synaptosomes. ATP/ADP ratios in both preparations were used to assess the energy levels and thus the oxygenation of brain slices and synaptosomes. ATP/ADP ratios similar to the intact brain and nerve terminals were found in slices and synaptosomes even after hours of superfusion with oxygenated buffer. Depolarization by 30 or 50 mM K+ induced release of histidine from slices and synaptosomes. The results confirm that under physiological energetic conditions, histidine is released both from slices and synaptosomes after depolarization with potassium.

Adenosine Diphosphate↗
PubMed1989

Molecular analysis of acute intermittent porphyria in a Finnish family with normal erythrocyte porphobilinogen deaminase.

Porphobilinogen deaminase, the third enzyme of the haem biosynthetic pathway, is encoded by two distinct mRNA species expressed in a tissue-specific manner from a single gene. These two mRNAs are transcribed from two promoters and only differ in their first exon. An inherited deficiency or porphobilinogen deaminase in man is responsible for the autosomal dominant disease acute intermittent porphyria. Different classes of mutations have been described at the protein level suggesting that this is a heterogeneous disease. In the present report, we describe the molecular abnormality responsible for a variant form of acute intermittent porphyria where the enzyme defect is restricted to non-erythroid cells. Upon cloning and sequencing the mutant allele of a patient from a large Finnish kindred, a single-base substitution within the 5'-splice donor sequence of intron 1 was found at the last position of exon 1 (CG----CT). The identification of this mutation allowed us to detect asymptomatic gene carriers among family members using in vitro amplification of DNA and hybridization of the target sequence to allele-specific oligonucleotides.

Ammonia-Lyases↗
PubMed1988

Acute hepatic porphyria and hepatocellular carcinoma.

In this study we examined the case histories of 163 living and 82 deceased adult Finnish patients with acute hepatic porphyria. There were 184 patients with acute intermittent porphyria and 61 patients with variegate porphyria. Among the 124 of the 163 living patients, who were traced 1984-1985, no hepatocellular carcinoma was found. Among the 82 deceased patients the cause of death was porphyria in 29 (36%), cardiovascular disease in 23 (29%) and hepatocellular carcinoma in 7 (9%). Of the 7 patients with hepatocellular carcinoma, 6 had acute intermittent porphyria and one had variegate porphyria. In acute hepatic porphyria, as compared with the total population, the calculated risk of hepatocellular carcinoma is increased 61-fold.

Adult↗
PubMed1983

Proton electrochemical potential of the inner mitochondrial membrane in isolated perfused rat hearts, as measured by exogenous probes.

The membrane potential (delta psi) and delta pH of the inner mitochondrial membrane were studied in isolated perfused rat hearts using exogenous labelled probes and tissue fractionation in non-aqueous media. The mitochondrial delta psi, measured by means of the subcellular distribution of [3H]triphenylmethylphosphonium (TPMP+), was 125 +/- 7 mV (negative inside) in hearts beating at 5 Hz and 150 +/- 3 mV (negative inside) in hearts beating at 1.5 Hz. The mitochondrial membrane delta pH, measured by means of the subcellular distribution of low concentrations of [1-14C]propionate, was 0.63 +/- 0.06 pH units (alkaline inside) in hearts beating at 5 Hz and 0.53 +/- 0.12 pH units (alkaline inside) in hearts beating at 1.5 Hz. The implication of proton and electron gradients in the regulation of cellular respiration is discussed. In combination with previous evidence on adenylate distribution in the isolated perfused rat heart, the results indicate that the mitochondrial electrogenic adenylate translocator is in near equilibrium with delta psi.

Adenylyl Cyclases↗
PubMedDate not supplied

Quantification of metabolites from single-voxel in vivo 1H NMR data of normal human brain by means of time-domain data analysis.

We present here a combination of time-domain signal analysis procedures for quantification of human brain in vivo 1H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for the N-acetylaspartate, creatine, and choline-containing compounds were 11.4 +/- 1.0, 6.5 +/- 0.5, and 1.7 +/- 0.2 mumol kg-1 wet weight, respectively. The time-domain analyses of in vivo 1H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties.

Aspartic Acid↗