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Biomedical subjects

H Hallman

Publications and source records attributed to H Hallman.

At least 19 recordsLinked to original sources
PubMed1990

Intensive chemotherapy with combinations containing anthracyclines for refractory and relapsing multiple myeloma. Finnish Leukaemia Group.

94 patients with refractory multiple myeloma were treated in a multicentre trial with combinations of cytotoxic drugs including anthracyclines. All were refractory to a 5-drug combination containing 3 alkylating agents, vincristine and methylprednisolone (MOCCA). With a combination of epirubicin and iphosphamide a 50% response was achieved in 9% of 22 patients. The response rate after schedule VAP (vincristine, doxorubicin and prednisolone) was 8% of 13 patients and that after schedule VAD (vincristine, doxorubicin and dexamethasone) 20% of 59 patients. The previous chemotherapy had lasted for less than 12 months in 13 cases from among all these patients, and 5 of these (38%) responded. In contrast, there were only 10 responders (12%) among the 81 patients with longer previous chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Measurements of the DNA amount in mono- and binucleate cells in the celiac superior mesenteric ganglion of the guinea pig.

The relative proportion, ultrastructure and DNA-content of the binucleate cells in the celiac superior mesenteric ganglion of the guinea pig was studied using light and electron microscopy as well as computerized image analysis of Feulgen stained cells. The number of mono - versus binucleate cells was found to vary with stage of development with about 40% of the cells being binucleate in adult animals and 50% in late prenatal stage. No difference in ultrastructure was observed between the nuclei of the two cell types. The binucleate cells contain twice the amount of DNA found in the mononucleate cells.

Animals↗
PubMed1989

Familial hypofibrinolysis and venous thrombosis.

Nine patients with, and 11 without, venous thromboses (DVT) from two families were studied. In family 1, four members with, and one without, DVT had t-PA activity below the lower limit of the controls (21.3 IU/ml, n = 19) after 20 min venous occlusion (VO). After VO t-PA antigen (t-PA:Ag) was below the lowest value of the controls (22.8 ng/ml) in all five cases with low t-PA activity. All the family members, both with and without thrombosis, had normal t-PA inhibitor activities (PAI). In family 2 t-PA activity after VO was low in three symptomatic and four asymptomatic family members. t-PA:Ag was also low in four of these. PAI level was normal in all but one family member. Mild type I von Willebrand's disease was discovered in four members of family 2. Deficient t-PA:Ag response was found in two of these. Antithrombin III, protein C and protein S were normal in both families. It is concluded that low fibrinolytic capacity, independent of PAI, is associated with familial DVT. Our data suggests autosomal dominant inheritance.

Adult↗
PubMed1988

Neuropeptide tyrosine in the rat adrenal gland--immunohistochemical and in situ hybridization studies.

The adrenal gland of the rat was analysed with immunohistochemistry and antisera to neuropeptide tyrosine, to the catecholamine-synthesizing enzymes tyrosine hydroxylase, phenyl-ethanolamine-N-methyltransferase, and to acetylcholinesterase and with in situ hybridization using a nick-translated 280 base pair deoxyribonucleic acid probe coding for exon 2 of the rat neuropeptide tyrosine gene. Neuropeptide tyrosine-like immunoreactivity was observed in three structures: chromaffin cells, medullary ganglion cells and nerve fibers. The chromaffin cells were of both the noradrenaline- and adrenaline-type. The ganglion cells did not seem to contain any catecholamine-synthesizing enzymes but exhibited a strong immunoreaction for acetylcholinesterase. They were thus in all probability cholinergic neurons. In situ hybridization using the nick-translated deoxyribonucleic acid probe to rat neuropeptide tyrosine messenger ribonucleic acid revealed a very high-grain density over the ganglion cells, a moderate density over the chromaffin cells and a low background over cortex, in agreement with the immuno-histochemical demonstration of neuropeptide tyrosine-like immunoreactivity both in chromaffin and ganglion cells. The intense neuropeptide tyrosine-like immunoreactivity and low content of neuropeptide tyrosine messenger ribonucleic acid suggest that the chromaffin cells have fairly large peptide stores but that the peptide turnover is low. In contrast, the ganglion cell bodies seem to contain low amounts of neuropeptide tyrosine-like immunoreactivity but exhibit a high neuropeptide tyrosine synthesis rate. Preliminary studies with the amine-depleting drug reserpine revealed an increase in messenger ribonucleic acid both in ganglion cells and medullary cells. In the chromaffin cells the highest activity was seen 3 and 4 days after injection, and the levels were down to normal after 8 days. The present findings demonstrate neuropeptide tyrosine synthesis and storage in two cell populations in the adrenal medulla. In situ hybridization with its cellular resolution can provide information on possible differential effects of drugs and experimental procedures on these two neuropeptide tyrosine stores.

Acetylcholinesterase↗
PubMed1988

Coexistence and gene expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase, and neuropeptide tyrosine in the rat and bovine adrenal gland: effects of reserpine.

Expression and regulation of the catecholamine-synthesizing enzymes phenylethanolamine N-methyltransferase (PNMTase; S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28) and tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the coexisting neuropeptide tyrosine (NPY) were studied in rat and bovine adrenal medulla. By using both immunohistochemistry and in situ hybridization, PNMTase- and NPY-positive cells exhibited a close overlap in bovine medulla and were preferentially localized in the outer two-thirds of the medulla. Although TyrOHase and its mRNA were observed in virtually all medullary gland cells, TyrOHase mRNA levels were much higher in the PNMTase- and NPY-positive cells. After administration of the catecholamine-depleting drug reserpine to rats, a brief increase, followed by a dramatic decrease, in the level of PNMTase mRNA was observed in the adrenal medulla. In contrast, mRNA for both TyrOHase and NPY only exhibited an increase, whereby the TyrOHase mRNA peak preceded that of NPY mRNA. Different regulatory mechanisms may thus operate for these three compounds coexisting in the adrenal medulla.

Adrenal Glands↗
PubMed1987

Distribution of [3H]cholecystokinin octapeptide binding sites in the hippocampal region of the rat brain as shown by in vitro receptor autoradiography.

The distribution of binding sites for the neuropeptide cholecystokinin octapeptide in the rat hippocampal region was studied by using quantitative in vitro receptor autoradiography. Biochemical analysis of [3H]cholecystokinin octapeptide binding to tissue sections of the hippocampal region showed it to be of high affinity, to be saturable and approximately 50% specific at saturating concentrations. The binding of [3H]cholecystokinin octapeptide to hippocampal sections was dose-dependently blocked by cholecystokinin octapeptide, cholecystokinin and by pentagastrin. The autoradiographic analysis showed high densities of [3H]cholecystokinin octapeptide binding sites in the hilus of the area dentata, the outer three layers of the retrosplenial area and the presubiculum, layer 3 of the medial, but not the lateral, entorhinal area and the deep and superficial parts of layer 1 and 2, respectively of both the medial and the lateral entorhinal area. Medium binding densities were found in the parasubiculum and remaining layers of the entorhinal area and low densities occurred in the subiculum and in all subfields of Ammon's horn. The angular bundle and fornix-fimbria lacked specific [3H] cholecystokinin octapeptide binding sites. A very similar pattern of binding densities was found for [3H]pentagastrin. Comparisons of the cholecystokinin octapeptide receptor distribution with the cholecystokinin octapeptide innervation of the hippocampal region suggest that there exists a relatively good concordance in some hippocampal subfields such as the presubiculum and the entorhinal area between binding sites for [3H]cholecystokinin octapeptide and cholecystokinin-immunoreactive afferent input.

Animals↗
PubMed1987

Treatment of multiple myeloma with an intensive 5-drug combination or intermittent melphalan and prednisone; a randomised multicentre trial. Finnish Leukaemia Group.

In a randomised multicentre trial a combination of methylprednisolone, vincristine, CCNU, cyclophosphamide and melphalan (MOCCA) was compared with intermittent melphalan and prednisone (MP) as primary treatment in multiple myeloma. In the MP arm the refractory or relapsed patients were treated with regimen MOCCA. The MOCCA arm produced a response rate of 75% among 64 patients and the MP arm a response rate of 54% among 66 patients. The median survival was 41 months in the MOCCA arm and 45 months in the patients primarily randomised to the MP arm. The initial response to MOCCA improved the survival, while this effect was not statistically significant in the MP arm. The results show that the median survival does not increase if aggressive chemotherapy is employed as the first line treatment in multiple myeloma.

Adult↗
PubMed1986

GM1 ganglioside counteracts selective neurotoxin-induced lesion of developing serotonin neurons in rat spinal cord.

The effect of exogenous monosialoganglioside GM1 on neurotoxin-induced lesioning of bulbo-spinal serotonergic neurons of newborn rats was studied by means of biochemical and immunocytochemical techniques. 5,7-dihydroxytryptamine (5,7-HT, a selective serotonin neurotoxin) treatment of newborn rats caused a pronounced reduction of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in the thoracic and lumbar spinal cord, while an increase of 5-HT and 5-HIAA was found in the pons medulla. These biochemical alterations were regionally correlated with similar changes in 5-HT nerve terminal density analyzed by image analysis. GM1 administration (30 mg/kg for 4 consecutive days) antagonized the reduction of 5-HT and 5-HIAA levels induced by 5,7-HT treatment in the lumbar spinal cord of 2-month-old rats, as well as the decrease of 5-HT nerve terminal density in both thoracic and lumbar spinal cord of 1- and 2-month-old rats. A minor counteracting effect of GM1 was found in the pons medulla where the neurotoxin induced an increase of 5-HT and 5-HIAA levels. These data support the hypothesis that GM1 may have a preventing action on retrograde degenerative processes following chemical lesion and/or a growth-stimulating effect on injured 5-HT neurons.

5,7-Dihydroxytryptamine↗
PubMed1986

Intranuclear localization of snRNP antigens.

Anti-Sm antibodies recognize a group of small, nuclear RNA-protein complexes (snRNPs) containing U1, U2, U4, U5, and U6 snRNAs. Anti-RNP antibodies only react with U1 snRNA-containing complexes. The intranuclear distribution of snRNP particles was studied by double immunofluorescence staining of human fibroblasts. Mouse monoclonal anti-Sm antibodies and polyclonal patient sera reacting with different peptides in the snRNP complexes were used. The immunofluorescence patterns obtained with fluorescein isothiocyanate-conjugated anti-mouse Ig and tetramethylrhodamine isothiocyanate-conjugated anti-human Ig second antibodies were examined using computer analysis of digitized images. With this approach the similarity of different patterns could be visualized and estimated with mathematical methods. It was found that human anti-Sm serum as well as three different anti-RNP sera produced speckled patterns overlapping with the anti-Sm monoclonal pattern. Thus, Sm antigenic intranuclear domains also reacted with anti-RNP antibodies, suggesting a high degree of co-localization of the antigenic structures. A partial overlap was found between speckles detected by mouse anti-Sm antibodies and a human La-antiserum. No significant co-localization occurred between speckles detected by mouse anti-Sm antibodies and speckles detected by human antisera reacting with Scl-70 and centromeric antigens. As the U1 snRNP complex is believed to play a role in the splicing of RNA polymerase II transcripts, it appears that the speckles detected by Sm and RNP antibodies may be regions of hnRNA synthesis and mRNA processing. Although no function has been demonstrated for the U2, U4, U5, and U6 snRNPs, the co-localization with the U1 RNA complexes shown in this report indicate that they too participate in some aspect of mRNA processing. The results suggest that computer-assisted analysis of nuclear immunofluorescence patterns will be a useful tool in studies of the spatial and functional organization of the interphase nucleus.

Antibodies, Monoclonal↗
PubMed1986

Quantitation of noradrenaline nerve density in mouse iris by computer-assisted image analysis.

The density of noradrenaline (NA)-containing nerve fibres in mouse iris was measured with computer-assisted image analysis techniques both under normal conditions and during regeneration. Noradrenaline nerves were visualized by Falck-Hillarp formaldehyde condensation technique in whole-mount spread preparations of mouse irides. The samples were analysed in a fluorescence microscope connected to a commercially available image analysis system (IBAS/Kontron). A software program was developed for specific detection of fluorescence and the nerve density was determined by calculating the area covered by fluorescence in percentage of total measuring field. The method showed good reproducibility as observed both when repeated measurements were performed in the same measuring field or when consecutive measurements on the same set of irides were performed. Also the inter-assay variation between control values in the different experiments was low. Loading of the adrenergic nerves by incubation in alpha-methyl-NA or conditions leading to partial diffusion of the fluorophore had minor effects on the nerve density values. The regeneration of the NA nerve fibres after a selective toxic sympathectomy with 6-hydroxydopamine was also studied. The nerve fibre density values measured by image analysis correlated well with the uptake of [3H]NA; the endogenous NA levels recovered much more slowly, however. It thus seems that endogenous transmitter levels might be a somewhat insensitive index of nerve terminal regrowth, at least in early stages of regeneration. The results indicate that image analysis is a powerful tool to quantitate a transmitter-identified nerve terminal network in a histological preparation.

Adrenergic Fibers↗
PubMed1985

Neurochemical and histochemical characterization of neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on brain catecholamine neurones in the mouse.

Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused a rapid and long-lasting reduction of both 3,4-dihydroxyphenylalanine (dopamine, DA) and noradrenaline (NA) in mouse brain, as observed histo- and neurochemically. The depleting effects were more pronounced after repeated MPTP administration and the most marked reductions were observed after 2 X 50 mg MPTP/kg s.c., when DA in striatum and NA in frontal cortex were reduced by greater than 90% 1 week after MPTP. Mice with such catecholamine depletions were markedly sedated and almost completely immobilized. The behavioural syndrome after MPTP resembled that seen after reserpine, a monoamine-depleting drug. MPTP also caused a long-lasting reduction of catecholamine uptake in striatal DA and cortical NA nerve terminals and reduced tyrosine hydroxylase activity in these regions. There was no evidence that MPTP caused any marked DA and NA cell body death. MPTP given acutely transiently elevated serotonin levels. The results are compatible with a neurotoxic action of MPTP on both DA and NA nerve terminals. The nigro-striatal DA and the locus coeruleus NA neurone systems appeared to be most susceptible. Synthesis and utilization of residual striatal DA and cortical NA were increased, as often observed in partially denervated monoamine-innervated brain regions. Both DA and NA showed a gradual recovery, which took months to become complete and may have been related to a regrowth of catecholamine nerve terminals.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1979

Developmental plasticity of central noradrenaline neurons after neonatal damage--changes in transmitter functions.

The effects of neonatal 6-hydroxydopamine (6-OH-DA) treatment (systemic administration) on noradrenaline (NA) metabolism, turn over, and receptor characteristics have been investigated in rat brain in the adult stage. This treatment is known to preferentially affect the locus coeruleus (LC) NA system leading to a marked NA denervation in the central cortex and hyperinnervation of NA nerve terminals in the pons and medulla oblongata without influencing the LC perikarya. The main NA metabolite, 3-methoxy-4-hydroxy-phenylglycol (MOPEG) was reduced by about 70% in the cerebral cortex after 6-OH-DA treatment at birth while the endogenous NA was almost completely depleted (-92%). The MOPEG levels were not significantly changed in the pons medulla after 6-OH-DA treatment in contrast to the 60% increase of the endogenous NA concentration. The relative reduction of NA in the cerebral cortex of 6-OH-DA treated rats increased in the cerebral cortex following administration of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (H44/68) compared to the control, while the H44/68 induced depletion of NA was reduced in the pons medulla after 6-OH-DA. The steady-state level of endogenous NA and the effect of H44/68 were unchanged in the LC perikarya after 6-OH-DA treatment. These results indicate that the NA turn over in remaining NA nerve terminals in the cerebral cortex is increased after 6-OH-DA, while decreased in the pons-medulla, possible related to changes in the activation of presynaptic alpha-adrenoreceptors in both regions. NA-induced formation of cAMP in vitro was found to be markedly increased in the cerebral cortex after 6-OH-DA, whereas no consistent change was observed in the pons medulla. Measurements of alpha- and beta-receptor binding in vitro using radioligand techniques showed an increase of binding sites (20%--50%) for both receptors in the neocortex aster 6-OH-DA, whereas no changes were observed in the pons medulla. The 6-OH-DA induced changes in NA turnover, cAMP generating systems, and receptor density may all represent compensatory processes following the altered development of the NA neurons induced by 6-OH-DA.

Aging↗
PubMed1979

Catecholamine turnover changes in hypothalamus and dorsal midline area of the caudal medulla oblongata of spontaneously hypertensive rats.

The central noradrenaline (NA) and adrenaline (A) turnover in 15--16-week-old stroke prone, spontaneously hypertensive (sp-SH) female rats in an advanced stage of hypertension was found to differ from that of normotensive Wistar-Kyoto (WKy) control rats. The catecholamine (CA) levels were measured after inhibition of dopamine-beta-hydroxylase (DBH) or phenylethanolamine-N-methyltransferase (PNMT). in the hypertensive rats the dopamine (DA) and NA levels and the NA turnover were reduced in the hypothalamus, while in the dorsal part of the caudal medulla oblongata NA levels and A turnover were reduced. Changes in hypothalamic DA and NA mechanisms and in A mechanisms in medulla oblongata may therefore be of importance in the blood pressure regulation of sp-SH rats.

Animals↗
PubMed1979

Catecholamines and hemorrhagic shock in awake and anesthetized rats.

Catecholamines in plasma and tissue were determined during hemorrhagic shock in the rat. Two groups of rats were compared. 1. Awake rats bled to 70 mm Hg for 4 hours. 2. Anesthetized rats (pentobarbital sodium 60 mg/kg) bled to 35 mm Hg for 4 hours. The mortality rate was similar in both groups. The bled volume was also similar. The awake rats responded with tachycardia upon bleeding while the anesthetized rats responded with bradycardia. The basal plasma levels of noradrenaline (NA), adrenaline (A) and dopamine (DA) in the awake rats were 2.87, 4.09, and 0.51 nmol/l respectively and in the anesthetized rats 0.97, 0.54, and 0.56 nmol/l respectively. At the onset of bleeding there was a more rapid increase of plasma A and NA in the awake rats than in the anesthetized rats. In the awake rats plasma A reached its peak value (70 nmol/l) at 1 hour and then decreased, while NA showed a slow continuous rise to 17 nmol/l at 4 hours. In the anesthetized rats plasma A remained at a high level (about 60 nmol/l) between 1 and 4 hours, while there was a continuous rise of NA to 17 nmol/l at 4 hours. In these rats a very high DA level (17 nmol/l) was also found at 4 hours. The tissue content of NA was not significantly decreased in the heart while a significant decrease was seen in the skeletal muscle after bleeding for 4 hours. In the heart there was a substantial increase of A after bleeding. The A content of the adrenals decreased to about 25% of the initial value in the awake animals. The results show that barbiturate anesthesia considerably depresses the initial sympatho-adrenal response to bleeding.

Adrenal Glands↗