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M Ahonen

Publications and source records attributed to M Ahonen.

32 records · Page 2Linked to original sources
PubMed1993

Preepithelial mucus-HCO-3 layer protects against intracellular acidosis in acid-exposed gastric mucosa.

The role of the preepithelial mucus-HCO-3 layer in protection against intracellular acidosis was investigated in isolated Necturus gastric antral mucosa exposed to luminal acid by simultaneous measurement of intracellular pH (pH(i)) and extracellular surface pH (pHs) in surface epithelium with microelectrode technique. Acidification of the luminal perfusate to pH 2.5 acidified pH(i) in surface epithelial cells from 7.33 +/- 0.02 to 7.20 +/- 0.04, whereas pHs fell from 6.75 +/- 0.21 to 5.20 +/- 0.25 (P < 0.01; n = 9), followed by a steady state for at least 2 h. Inhibition of epithelial HCO-3 secretion and transport by removal of serosal HCO-3 and CO2 (HEPES and O2 substitution) during acid exposure provoked a progressive acidification of pHs from 5.60 +/- 0.41 to 2.74 +/- 0.14 in 30 min (P < 0.01; n = 9), which was accompanied, after a 5- to 10-min delay, by acidification of pH(i) from 7.21 +/- 0.03 to 5.68 +/- 0.26 (P < 0.01). Digestion of the surface mucus gel by pepsin (5% wt/vol) at pH 2.5 caused a slow acidification of pHs from 5.22 +/- 0.59 to 3.60 +/- 0.46 within 2 h. This was followed by a more rapid acidification to 2.53 +/- 0.38 (P < 0.01; n = 7), with concomitant acidification of pH(i) from 7.19 +/- 0.05 to 6.03 +/- 0.33 (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1991

Neurofilament immunoreactivity and acetylcholinesterase activity in the developing sympathetic tissues of the rat.

In this study, the ontogenetic appearance of three neuronal markers, tyrosine hydroxylase (TH), neurofilament (NF) proteins and acetylcholinesterase (AChE), have been compared in the neural tube and derivatives of the neural crest with special consideration on developing rat sympathetic tissues. The tree markers appeared for the first time on embryonic day E 12.5. At this age, NF immunoreactivity was located in the cells on the ventro- and dorsolateral edges of the neural tube, i.e., in the regions where the cells had reached the postmitotic stage. In addition, on day E 12.5, NF-immunoreactive fibers were located in the dorsal and ventral roots and the spinal and sympathetic ganglia. This suggests rapid extension of neurites. In contrast to NF, AChE first appeared on day E 12.5 in cell somata of spinal and sympathetic ganglia and only after that in axons. Thus, it can be considered as a marker of differentiating neuronal cell bodies. In the developing sympathoadrenal cells, TH is expressed before NF and AChE. However, the migrating TH immunoreactive sympathetic cells are constantly followed by NF immunoreactive fibers, suggesting that sympathetic tissues may receive innervation from preganglionic axons at the very beginning of their ontogeny. During the later development, all sympathetic tissues contain two major cell groups: 1) one with a moderate TH immunoreactivity, NF immunoreactivity and AChE activity and 2) the other with an intense TH immunoreactivity but lacking NF immunoreactivity or AChE activity. The former includes principal neurons, neuron-like cells of the paraganglia and noradrenaline cells of the adrenal medullae, and the latter includes ganglionic small intensely fluorescent (SIF) cells, paraganglionic cells and medullary adrenaline cells.

Acetylcholinesterase↗
PubMed1991

Distribution of histamine in the developing peripheral nervous system.

The presence and ontogenetic distribution of histamine was studied in the developing peripheral nervous system of the rat by using an indirect immunofluorescence technique and a specific rabbit anti-histamine antiserum. Histamine immunoreactivity (IR) first appeared in peripheral nerves on embryonic day 14. The number and intensity of histamine-immunoreactive nerves was highest on embryonic days 16-18. During development starting from embryonic day 14, motoneurones in ventral horns of the spinal cord at cervical, thoracic and lumbar levels contained histamine IR. A subpopulation of sensory neurones in dorsal root ganglia exhibited histamine IR. Histamine IR was also present in nerve fibres of ventral and dorsal roots of spinal cord, as well as in spinal nerves. Population of neurons and nerve fibres in sympathetic and pelvic ganglia as well as in myenteric ganglia of the intestine were also labelled with the histamine antiserum. In peripheral target organs, histamine IR was observed in nerve fibres around bronchi of the lungs, in the atria of the heart, in the adrenal gland, in the intestinal wall, in muscular tissues and in subepithelial tissue of the skin. The results of this study indicate that histamine is widely distributed in different types of neurons and nerve fibers of the developing peripheral nervous system.

Animals↗
PubMed1991

Histamine in the developing sympathoadrenal system.

The ontogenetic distribution of histamine in correlation with catecholamines in the developing rat sympathoadrenal system was analyzed by using an indirect immunohistochemical method and a specific rabbit anti-histamine antiserum. Tyrosine hydroxylase (TH) immunoreactivity was used as a marker of catecholamine synthesis. TH immunoreactivity appeared in retroperitoneal sympathetic tissues on embryonic day 12.5 (E 12.5) when it was found in cells of lumbar chain ganglia. In preaortic sympathetic tissue. TH immunoreactivity was observed on day E 13.5 and in adrenal medullae on day E 14.5. Histamine immunoreactivity was expressed in all of these tissues beginning from day E 14.5. First it was found mainly in nerve fibers, but also in some cells. During the embryonic development the number of histamine-immunoreactive cells increased in all sympathetic tissues studied. In newborn rats, histamine immunoreactivity was restricted to a subpopulation of sympathetic cells, i.e. small intensely fluorescent (SIF) cells of sympathetic ganglia, paraganglion-type cells and some adrenaline-synthesizing cells of the adrenal medulla.

Adrenal Glands↗
PubMed1989

L-glutamate decarboxylase immunoreactivity in developing sympathetic tissues of the rat.

An indirect immunofluorescence method was used to study the appearance and distribution of L-glutamate decarboxylase (GAD), the enzyme synthesizing gamma-aminobutyric acid, in developing rat retroperitoneal sympathetic tissues. GAD immunoreactivity was analyzed in correlation with immunoreactivity to the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), in the main retroperitoneal paraganglion, adrenal medullae and abdominal sympathetic ganglia. In different abdominal sympathetic tissues TH-immunoreactive cells first appeared on embryonic days 12.5-14.5, while GAD immunoreactivity was first observed in all these tissues in 14.5-day-old embryos (E 14.5). This suggests that the first expression of GAD is not coupled to the onset of catecholamine synthesis. In developing chain ganglia, GAD immunoreactivity was localized prenatally only in cell clusters with bright TH immunoreactivity, suggesting that GAD is expressed only in the cell lineage leading to ganglionic small intensely fluorescent (SIF) cells. The coeliac-superior mesenteric ganglion complex developed from the preaortic sympathetic tissue, starting from E 16.5 embryos, when the cranial, moderately TH-immunoreactive cells of this tissue were seen to form compact cell islets around the branches of the abdominal aorta. The caudal, intensely TH-immunoreactive cells of preaortic sympathetic tissue were seen to form the main retroperitoneal paraganglion from day E 15.5. During the prenatal period GAD immunoreactivity in preaortic sympathetic tissue was present caudally only in these paraganglionic cells and cranially in some brightly TH-immunoreactive cells, representing SIF and/or paraganglionic cells. In the adrenal medulla, only some of the TH-immunoreactive cells showed GAD immunoreactivity during early developmental stages. The moderately TH-immunoreactive, noradrenaline-synthesizing, cell clusters were seen for the first time in E 16.5 embryos, and they exhibited no GAD immunoreactivity. Thereafter, GAD was expressed only in the intensely TH-immunoreactive, adrenaline-synthesizing, cell clusters. The results of this study indicate that in the developing rat sympathetic tissues GAD is present only in the cell lineages which differentiate into SIF cells of abdominal sympathetic ganglia, preaortic paraganglionic cells and adrenaline cells of the adrenal medulla.

Adrenal Medulla↗
PubMed1989

Immunocytochemical localization of L-glutamate decarboxylase and catecholamine-synthesizing enzymes in the retroperitoneal sympathetic tissue of the newborn rat.

The localization of L-glutamate decarboxylase (GAD), the enzyme synthesizing gamma-aminobutyric acid, was studied in newborn rat retroperitoneal sympathetic tissue, i.e. the main retroperitoneal paraganglion, adrenal medullae and abdominal sympathetic ganglia using the indirect immunofluorescence method. The coexistence of GAD with the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) was analyzed in consecutive sections or by staining one section consecutively with different antisera. GAD immunoreactivity was observed only in some cell types of each organ studied. In the main retroperitoneal paraganglion, the small, intensely TH-immunoreactive, paraganglion-type cells were GAD-immunoreactive, while the larger moderately TH-immunoreactive, neuron-like cells were non-reactive for GAD. In the adrenal medulla, GAD immunoreactivity was localized only in the adrenaline-synthesizing, PNMT-immunoreactive chromaffin cells. The noradrenaline-synthesizing, i.e. the TH-immunoreactive cells with no PNMT immunoreactivity, were non-reactive for GAD. In the abdominal sympathetic ganglia, some small intensely TH-immunoreactive cells were GAD-immunoreactive, while the principal neurons were non-reactive for GAD. These results provide immunohistochemical evidence that GAD is present and is colocalized with catecholamine-synthesizing enzymes in various sympathetic tissues of the newborn rat. The present results indicate that GAD is localized in adrenaline-synthesizing cells of all the sympathetic tissues studied. A fraction of noradrenaline-synthesizing cells of retroperitoneal sympathetic tissues, excluding the adrenal medulla, also contains GAD.

Adrenal Medulla↗
PubMed1989

Developmental changes in 5-hydroxytryptamine immunoreactivity of sympathetic cells.

5-Hydroxytryptamine was demonstrated immunohistochemically in developing sympathetic chain ganglia, adrenal medullae and retroperitoneal paraganglionic tissue. Initially, all catecholamine-synthesizing cells were immunoreactive to 5-hydroxytryptamine, but during the maturation some sympathetic cell types lose this property. In the ganglia, small intensely fluorescent cells retain their 5-hydroxytryptamine content throughout maturation. This property is expressed transitionally in some neonatal principal neurons, but can be triggered even in adult neurons, e.g. after loading with L-tryptophan. In the adrenal medulla, immunoreactivity to 5-hydroxytryptamine is carried over to the adrenaline-synthesizing cells, while in the main retroperitoneal paraganglion it is observed in both adrenaline and noradrenaline cells. These results suggest that initial expression of 5-hydroxytryptamine immunoreactivity is coupled to the onset of catecholamine synthesis, but is regulated differently in each mature sympathetic organ.

Adrenal Medulla↗
PubMed1988

5-Hydroxytryptamine and catecholamines in developing sympathetic cells of the rat.

Appearance of 5-hydroxytryptamine (5-HT) in developing sympathetic cells of prenatal rats was studied using the indirect immunofluorescence method. In consecutive sections, tyrosine hydroxylase (TH) immunoreactivity was considered as a marker for catecholamine-synthesizing cells in general, while phenylethanolamine N-methyltransferase (PNMT) immunoreactivity was used as an indicator of adrenaline synthesis. 5-HT immunoreactivity was observed for the first time in 12.5-day-old embryos in developing sympathetic chain ganglia. On day 13.5, 5-HT-immunoreactive cells were first seen on the preaortic region and on day 14.5 in the developing adrenal gland. Comparison with consecutive sections stained for TH revealed that all TH-immunoreactive cells were also 5-HT-immunoreactive. During later development, however, 5-HT immunoreactivity was retained by some cell types in each sympathetic tissue. In the ganglia, most developing principal nerve cells gradually lost their 5-HT immunoreactivity, while all so-called small intensely fluorescent (SIF) cells remained intensely 5-HT-immunoreactive. In the adrenal medulla, all catecholamine-containing cells showed 5-HT immunoreactivity until day 16.5. The first adrenaline-synthesizing cells appeared at this stage. Occasionally on day 16.5 and constantly on day 17.5 noradrenaline cell islets were distinguished among adrenaline cells. The adrenaline cells retained intense 5-HT immunoreactivity, while the noradrenaline cells were non-reactive to it. In the main retroperitoneal paraganglion, two noradrenaline cell populations were distinguished from day 15.5, one being 5-HT-immunoreactive and the other non-reactive. A third population appeared in this tissue at the time of birth, consisting of adrenaline-synthesizing cells which were also 5-HT-immunoreactive. These results indicate that the 3 sympathetic tissues undergo similar developmental changes: 5-HT immunoreactivity occurs in conjunction with the initiation of catecholamine synthesis and appears first in all catecholamine cells. During maturation it is confined to certain subpopulations in each tissue, i.e. the SIF cells and some principal nerve cells of the ganglion, the adrenaline cells of the adrenal medulla, the adrenaline cells and some noradrenaline cells of the paraganglionic tissue.

Animals↗
PubMed1987

Pre- and postnatal development of rat retroperitoneal paraganglia.

The prenatal and postnatal development of the rat retroperitoneal paraganglia were studied using the formaldehyde-induced catecholamine fluorescence (FIF) method. In addition, the transmitter composition of the paraganglionic cells of the newborn rat was analyzed by immunohistochemical demonstration of the catecholamine-synthesizing enzymes. The first fluorescent preaortic cells were detected in the 13.5-day-old embryos. One day later these cells constituted a distinct organ with moderately fluorescent cells, and in 15.5-day-old embryos this organ consisted cranially of moderately fluorescent and caudally of brightly fluorescent cells. The organ reached its largest size at birth and afterwards fibrous material increased between the fluorescent cells. In 4-week-old animals, only small clusters of fluorescent cells were observed in the preaortic area although many small paraganglia were situated cranially near the coeliac ganglion. In the organ of the newborn rat, many cells showed bright FIF. In addition, some cells with only slight or moderate fluorescence as well as non-fluorescent cells were detected. The analysis of immunoreactivity to the catecholamine-synthesizing enzymes showed that there was a cell population with intense reactivity to both tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). These cells were considered as paraganglion-type cells. Some of them were also immunoreactive to phenylethanolamine N-methyltransferase (PNMT). In addition, there were cells with weak to moderate reactivity to TH and DBH but not to PNMT. Also totally negative cells were constantly seen. These findings were confirmed by using consecutive sections for the localization of different enzymes and by using the Tramu method to elute previous staining and by restaining the same sections with the other antibodies. It is concluded that the retroperitoneal paraganglia of newborn rat consist of many paraganglion-type cells containing noradrenaline, some of them containing also adrenaline, a few neuron-like cells with TH and DBH immunoreactivity, and cells containing no catecholamines.

Animals↗
PubMedDate not supplied

Vitamin D and prostate cancer.

Our recent epidemiological study (Ahonen et al., Cancer Causes Control 11(2000) (847-852)) suggests that vitamin D deficiency may increase the risk of initiation and progression of prostate cancer. The nested case-control study was based on a 13-year follow-up of about 19000 middle-aged men free of clinically verified prostate cancer. More than one-half of the serum samples had 25OH-vitamin D (25-VD) levels below 50 nmol/l, suggesting VD deficiency. Prostate cancer risk was highest among the group of younger men (40-51 years) with low serum 25-VD, whereas low serum 25-VD appeared not to increase the risk of prostate cancer in older men (>51 years). This suggests that VD has a protective role against prostate cancer only before the andropause, when serum androgen concentrations are higher. The lowest 25-VD concentrations in the younger men were associated with more aggressive prostate cancer. Furthermore, the high 25-VD levels delayed the appearance of clinically verified prostate cancer by 1.8 years. Since these results suggest that vitamin D has a protective role against prostate cancer, we tried to determine whether full spectrum lighting (FSL) during working hours could increase serum 25-VD concentrations. After 1-month exposure, there was no significant increase in the serum 25-VD level, although there was a bias towards slightly increasing values in the test group as opposed to decreasing values in controls. There was no significant change in the skin urocanic acid production. The possibility to use FSL in cancer prevention is discussed. In order to clarify the mechanism of VD action on cell proliferation and differentiation, we performed studies with the rat and human prostates as well prostate cancer cell lines. It is possible that 25-VD may have a direct role in the host anticancer defence activity, but the metabolism of vitamin D in the prostate may also play an important role in its action. We raised antibodies against human 1alpha-hydroxylase and 24-hydroxylase. Our preliminary results suggest that vitamin D is actively metabolised in the prostate. Vitamin D appears to upregulate androgen receptor expression, whereas androgens seem to upregulate vitamin D receptor (VDR). This may at least partially explain the androgen dependence of VD action. VD alone or administered with androgen causes a suppression of epithelial cell proliferation. VD can activate mitogen-activated kinases, erk-1 and erk-2, within minutes and p38 within hours. Also, auto/paracrine regulation might be involved, since keratinocyte growth factor (mRNA and protein) was clearly induced by VD. Based on these studies, a putative model for VD action on cell proliferation and differentiation is presented.

Adult↗