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Biomedical subjects

P Alm

Publications and source records attributed to P Alm.

At least 145 records · Page 8Linked to original sources

Ontogenetic development of the guinea pig uterine innervation. An immunohistochemical study of different neuronal markers, neuropeptides and S-100 protein.

The ontogenetic development of the guinea pig uterine autonomic innervation was studied immunohistochemically using neurofibrillary protein (NF) and neuron specific enolase (NSE) as general neuronal markers, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) as specific markers for adrenergic innervation and S-100 protein as marker for Schwann cell structure and/or function. In addition, comparisons were made of the development of the different populations of peptide-containing nerves. The structure and time of appearance were similar for nerves with NF-, NSE-, TH- and DBH-immunoreactivities, which were first present in the organ periphery as coarse nerve trunks, then extending centrally and branching into non-varicose nerves. From these, varicose nerves developed first in relation to vessels and then in association with the myometrial smooth musculature. Development was completed earlier in the cervix than in the uterine horns suggesting differences in local environment. In comparison, S-100 nerve-immunoreactivity appeared later but attained complete development more rapidly than axonal structures. Neuropeptide Y-immunoreactive nerves showed a similar developmental pattern to presumed adrenergic nerves, further verifying the assumption of intraneuronal localization of NPY in uterine adrenergic nerves. Other peptide-containing nerves were developed later probably reflecting differences in neuronal growth properties.

Animals↗

Effects of pregnancy on the extrinsic innervation of the guinea pig uterus. A histochemical, immunohistochemical and ultrastructural study.

The extrinsic innervation of the guinea pig uterus was studied by immunohistochemical, ultrastructural and enzyme histochemical methods. The extrinsic innervation was organized in two major ways. One consisted of nerve trunks and non-varicose nerve fibres running in the suspensory ligament, and the other of a plexus of varicose nerve fibres surrounding vessels, and non-vessel-related non-varicose nerve fibres in the mesouterus. The use of different neuronal and Schwann cell markers showed that the extrinsic innervation was predominantly adrenergic and contained only few peptidergic nerves. Acetylcholinesterase-positive (cholinergic) nerves were only found around the uterine artery. In late pregnancy, the extrinsic nerves of the mesouterus adjacent to foetus-containing uterine horns underwent pronounced degenerative changes comprising both Schwann cell and axonal structures. In comparison, no changes were found in extrinsic nerves of mesouteri adjacent to non-foetus-bearing uterine horns or in extrinsic nerves in the suspensory ligaments. Further, chemical sympathectomy produced axonal degeneration but no changes in the Schwann cells. In conclusion, the pregnancy-induced nerve degeneration is of a very special type different from that following chemical sympathectomy and represents a local phenomenon related to the conceptus. Hypothetically, this could be of importance for counteracting disturbances in placental blood flow.

Animals↗

Organization of the guinea-pig uterine innervation. Distribution of immunoreactivities for different neuronal markers. Effects of chemical- and pregnancy-induced sympathectomy.

The structural organization of the guinea-pig uterine innervation was investigated by an immunofluorescence method using neurofibrillary protein (NF) and neuron-specific enolase (NSE) as general neuronal markers. NF- and NSE-immunoreactive nerve trunks and non-varicose nerves formed continuous networks similar to nerves with analogue morphology and with immunoreactivities for tyrosine hydroxylase (TH; adrenergic nerves) and neuropeptide Y (NPY). NF- and NSE-immunoreactive non-varicose nerves occurred in the myometrium and along vessels, where TH- and NPY-immunoreactive varicose nerves were also comparatively frequent. After chemical sympathectomy all TH- and NPY-immunoreactive varicose nerves and most NF- and NSE-immunoreactive non-varicose nerves disappeared, suggesting colocalization of TH, NPY, NF and NSE immunoreactivities. During pregnancy all NF-, NSE-, TH- and NPY-immunoreactive nerve structures disappeared in the foetus-bearing uterine horns whereas in the cervix and non-foetus-bearing uterine horns only the myometrial TH- and NPY-immunoreactive varicose nerves disappeared. After parturition there was a complete structural restoration of all types of immunoreactive nerves in previously non-foetus-related tissue. The reinnervation of this tissue followed a similar time-course to that after chemical sympathectomy. In contrast, the reinnervation of previously foetus-related tissue was much slower and incomplete. In conclusion, the whole autonomic uterine innervation undergoes overt structural changes during pregnancy and these changes are related to the foetus-bearing regions.

Adrenergic Fibers↗

Uterine microcurettage with combined endometrial histopathology and cytology. An alternative to conventional curettage.

A new disposable mechanical curette, the Inocurette, was used to obtain endometrial samples for histopathology and cytology. The instrument was tested on 120 patients; 37 patients were known from a previous conventional curettage (D & C) to have an endometrial cancer and 83 patients were referred to the County Hospital of Trelleborg for curettage because of dysfunctional bleedings. In all 120 patients a D & C followed the microcurettage procedure. The samples were randomized, coded and analyzed blind without any clinical information. In all but 3 patients with a known endometrial cancer, sufficient microcurettage sample material for either histopathology or cytology was obtained. In all but one of these 34 patients either a malignant diagnosis or seriously atypical cells were found. Using only cytology five out of 34 samples were designated adequate but normal. In a further 5 of the 37 patients the samples obtained at the subsequent D & C were inadequate for diagnosis; one sample was denoted as normal. In the 83 patients with dysfunctional bleedings, sufficient material for diagnosis after microcurettage, cytology and D & C was obtained in 74, 83 and 79 patients respectively. One endometrial cancer was disclosed by all three methods. Inocurette sampling causes little discomfort and requires no special training. The combined microcurettage--cytology procedure may be recommended as an alternative to conventional curettage, though, for the time being, D & C should not be replaced for cytology alone.

Curettage↗

Defective synthesis of apolipoprotein A-I in jejunal mucosa in coeliac disease.

Apolipoprotein A-I was studied in biopsy specimens from the duodenojejunal junction by means of an indirect immunoperoxidase technique. In normal control subjects apolipoprotein A-I was immunohistochemically detected only in the absorptive cells at the tips of villi and was mainly localized supranuclearly. In 14 patients with coeliac disease apolipoprotein A-I was virtually undetectable. This implies that the inflammatory lesion in coeliac disease decreases the intestinal mass of apolipoprotein A-I, because it destroys the villous absorptive cells. Apolipoprotein A-I concentrations in plasma were also decreased (by 40%) in patients with coeliac disease, suggesting that the intestine has a role in maintaining plasma apolipoprotein A-I levels.

Adult↗

S-100-immunoreactive nerves in the guinea-pig uterus with reference to ultrastructural correlations: effects of chemical sympathectomy and pregnancy.

In the guinea-pig uterus, by use of an indirect immunofluorescence method, S-100 immunoreactivity was found to be restricted to nerves that corresponded in number, distribution and type to adrenergic axons and pre-terminals. With advancing pregnancy S-100 immunoreactivity completely disappeared in uterine tissue adjacent to a fetus, in parallel with an ultrastructural degeneration of the adrenergic innervation. In the cervix and the uterine horn devoid of a fetus, however, the number and distribution of S-100-immunoreactive nerves was seemingly unchanged and no ultrastructural changes were found in adrenergic nerves. In contrast, chemical sympathectomy produced by 6-hydroxydopamine did not change S-100 immunoreactivity of uterine nerves. These findings suggest that there are differences in the denervation effected by chemical and by pregnancy-induced sympathectomy. The latter probably represents a special type of adrenergic denervation by inducing a degeneration of Schwann cells in addition to destruction of neuronal structures. This may explain the differences in the speed of regeneration of uterine adrenergic nerves following the two types of denervation.

Animals↗

Urinary bladder innervation in children.

Muscle strips from the fundus, trigone, and distal ureter obtained from children at operation for vesicoureteric reflux were studied using histochemical and immunohistochemical methods, and electrical nerve stimulation in an organ bath. A rich supply of cholinergic nerves was found and the transmitter causing contraction of the detrusor muscle was regarded as being acetylcholine. The adrenergic innervation was very sparse except around the ureteric orifices. No contractile alpha-adrenoceptors could be detected but beta-receptor-mediated relaxation was found. The type was not beta 1 or beta 2, suggesting a third type of beta-receptor. Peptidergic nerves containing vasoactive intestinal peptide (VIP) were demonstrated in a few nerve terminals. No nerves containing enkephalin, somatostatin, or substance P were found. VIP affected the detrusor muscle, indicating a possible role as a modulator of transmitter action. Imipramine, used for enuresis, had no anticholinergic effect on the bladder in the doses used clinically. The anticholinergic and calcium antagonistic drug terodiline inhibited all muscle activity, making it suitable for treatment of diurnal enuresis.

Acetylcholinesterase↗

Changes in cholinergic innervation and neuropharmacologic properties in idiopathic hypotonic urinary bladders.

Tissue specimens from hypotonic and normotonic human urinary bladders were investigated histochemically, chemically and neuropharmacologically. In hypotonic bladders the density of acetylcholinesterase (AChE)-positive nerves was markedly reduced and the nerve AChE staining intensity was weak. The concentration of acetylcholine was significantly lower than in specimens from normotonic bladders. At field stimulation the contractions were weak. The observations indicated that sparse cholinergic innervation and reduced acetylcholine synthesis are important for the impaired contractility in idiopathic dystonic bladder.

Acetylcholine↗

Lung tumor presentation in relation to histology and smoking habit of operable and inoperable patients.

In two separate groups of lung cancer patients, the cranio-caudal site of tumor presentation was related to smoking habits. Group I consisted of 47 inoperable lung cancer patients. In this group apical lung tumor presentation was significantly more common in nonsmokers than in smokers (p less than 0.04). The proportion of women and patients with adenocarcinoma was higher for nonsmokers (p less than 0.01 and p less than 0.01, respectively). In order to validate these findings the site of tumor presentation in relation to smoking habits was studied for a separate group of 369 lung cancer patients. All these patients (group II) had operable tumors. In general, these patients were younger and came from more urban areas than the patients in group I. In group II, upper lobe tumor presentation was not more common among nonsmokers compared with tumor presentation in smokers (p greater than 0.05). However, there were more patients with adenocarcinomas and women among nonsmokers (p less than 0.0001 and p less than 0.0001, respectively). The findings indicate that either the tumor site of presentation in operable and in inoperable lung cancer patients has different epidemiological characteristics, or that, due to chance, a difference in the groups has been observed. However, consistently in the two groups, women with adenocarcinomas who were smokers were younger than other women with adenocarcinomas.

Aged↗

Contractile response in isolated human groin lymphatics.

Lymphatics from the human superficial groin removed at operation in 21 patients (one with lymphedema) were examined in vitro. Histochemically no nerves were identified with either specific catecholamine fluorescence or immunoreactivity to tyrosine hydroxylase or dopamine beta-hydroxylase. Ring preparations of the lymphatics were mounted in tissue baths and isometric induced contractions were recorded after administration of K+ (124 mM), acetylcholine, selected amines and prostanoids. Noradrenaline (NA), adrenaline, dopamine, and acetylcholine had no or only weak contractile effects. In some segments, serotonin induced contractions. Prostaglandin E2 showed no contractile effect and prostaglandin F2 alpha induced contraction in most of the tested lymphatics. The prostaglandin-endoperoxide analogue U44069 uniformly elicited marked concentration-dependent contraction. In the lymphatic segment from the patient with lymphedema, a slightly greater contractile response to NA and serotonin was observed. The results overall suggest an absence of sympathetic innervation and contraction-mediating alpha adrenergic receptors in human superficial groin lymphatics, and support that certain prostanoids may be important regulators of human lymphatic contractility.

Acetylcholine↗

Histochemical demonstration of a concomitant reduction in neural vasoactive intestinal polypeptide, acetylcholinesterase, and noradrenaline of cat uterus during pregnancy.

Noradrenaline, acetylcholinesterase, and vasoactive intestinal polypeptide (VIP) were visualized in uterine nerves of cats by histochemical techniques. Alterations were followed in different regions of the organs at various stages of pregnancy and compared with the situation in non-pregnant controls. Positively stained nerve fibres, the adrenergic type being particularly well developed, were found along the muscle bundles and around blood vessels in the smooth muscle layers, as well as in the mucosa, of both uterine horns and cervix. The nerve supply was especially prominent in the upper part of the cervix. The distribution of VIP-immunoreactive and acetylcholinesterase-positive nerve fibres resembled each other, but they were less numerous than the adrenergic fibres. In the course of pregnancy there was a marked reduction in the number of all positively reacting nerves, so that almost no fibres were visible in the uterine horns near term. A small number of positive nerve fibres was found to remain, however, in the wall of the sterile (empty) horn during unilateral pregnancy. The reduction was less prominent in the cervix, particularly its lower part. Distinct changes were encountered already during early and mid pregnancy in those parts of the uterine wall distended by the growing conceptus, where almost no fibres were seen. The nerve supply was more intact in the non-distended portions located between the fetuses, and especially in the empty horn of unilateral pregnancy. No overt reduction in the number of positively stained nerve fibres was found in the cervix at these pregnancy stages. The results show that marked alterations take place in the uterine autonomic innervation during such an entirely physiological event as pregnancy. There is reason to assume that the histochemical observations reflect both structural and functional alterations in the innervation related both to the type of nerves involved and to the localization of the conceptus.

Acetylcholinesterase↗

Innervation of the child urinary bladder.

Muscle strips from the fundus, trigonum and distal ureters obtained from children at operations for vesico-ureteric reflux were studied using histochemical and immunohistochemical methods, and electrical nerve stimulation in an organ bath. A rich supply of cholinergic nerves was found and despite a partial atropine resistance the neurophysiological experiments indicated that the transmitter causing contraction of the detrusor muscle is acetylcholine. Imipramine, which is used in the treatment of enuresis, had no anticholinergic effect on the bladder in the doses used clinically. The adrenergic innervation was very sparse except around the ureter orifices. No contractile alpha-adrenoceptors could be detected but beta receptor mediated relaxation was found, which was neither of the beta 1 nor beta 2 type. A third type of beta receptor is postulated. Peptidergic nerves containing vasoactive intestinal peptide, VIP, were demonstrated in a few nerve terminals running along bundles of smooth muscle. No nerves containing enkephaline, somatostatine or substance P were found. VIP affected the detrusor muscle indicating a possible role as a modulator of transmitter action, while substance P had no effect. The anticholinergic and calcium antagonistic drug terodiline inhibited all muscle activity, whether it was induced by nerve stimulation, cholinergic drugs or a potassium rich solution, making it suitable for treatment of diurnal enuresis.

Adrenergic Fibers↗

Levels of neural vasoactive intestinal polypeptide in rat uterus are markedly changed in association with pregnancy as shown by immunocytochemistry and radioimmunoassay.

Immunocytochemical studies have shown that the rat uterus is well innervated by nerve fibers containing vasoactive intestinal polypeptide (VIP). The fibers were associated with both vascular and nonvascular smooth muscle cells, and they were somewhat more numerous in the cervix compared to the uterine horns. This was confirmed in radioimmunologic determinations. Pregnancy induced a marked, almost 50% reduction in the total content of VIP in the uterine horns, which was associated with an almost complete disappearance of immunocytochemically visible nerve fibers in this part of the uterus. The innervation normalized within 25 days following delivery. Less marked changes occurred in the VIP innervation of the cervical region, where the concentration of the peptide was reduced mainly as a result of the increased tissue weight during pregnancy.

Animals↗

Basal cell carcinoma of the vulva.

A clinical and histopathologic study of material from a series of 21 patients with basal cell carcinoma treated from 1960 until 1979 are reviewed. In 3 patients 'mixed' tumor was recorded. The histopathologic diagnosis: basosquamous carcinoma and the behavior of this carcinoma are discussed. The mean age of the patients was 76 years. Presenting symptomatology consisted primarily of bleeding, burning or itching, and ulcerations. No case of pure basal cell carcinoma gave metastasis to the regional lymph nodes, in no case could the cause of death be attributed directly to this kind of lesion. A conservative approach consisting of wide local excision is suggested.

Aged↗

Plasma steroid hormones, cytosol receptors, and thymidine incorporation rate in endometrial carcinoma.

Histopathologically evaluated endometrial carcinomas were analyzed for the presence of estradiol and progesterone receptors and for tumor thymidine incorporation rate. Plasma estradiol and progesterone concentrations were also measured. With the use of an improved assay, all endometrial carcinomas were found to contain estradiol receptors; 81 of 92 (88%) contained measurable concentrations of progesterone receptors. The concentrations of both receptors were positively correlated to the degree of differentiation. The moderately and poorly differentiated tumours could be further divided into subgroups with low and high concentrations of receptors, which might be a reflection of an independent biologic characteristic of a tumor. These subgroups did not differ in any of the other variables studied, including the age of the patients. The plasma concentrations of estradiol showed a positive correlation to the degree of differentiation and to the concentration of both receptors. It is suggested that improved analyses of estradiol and progesterone receptors in endometrial carcinomas may add information to the conventional histopathologic and clinical classification which will be of significant value in the proper treatment of the disease.

Aged↗

Hypophyseal tumor and gynecomastia preceding bilateral breast cancer development in a man.

The case is reported of a 48-year-old man who, 26 years after treatment for a hypophyseal tumor and 11 years after the onset of bilateral gynecomastia, developed cancer of the left breast. Ten years after the first breast cancer operation a new cancer developed in his right breast. Hormonal investigation at the time of the second breast cancer operation revealed a low S-FSH and a relative estrogen excess compared to testosterone. Values of thyroid and adrenal hormones were essentially normal, while P-prolactin was elevated. Stimulatory tests of the hypophyseal function were in accordance with a partial hypophyseal insufficiency affecting the hypophyseal-gonadal axis. Also, a weak elevation of S-HGH was noted by an insulin tolerance test. Immunohistochemical analysis of the pituitary tumor 36 years later showed that the tumor could be classified as a prolactinoma. Cytogenetic analysis revealed a normal male chromosome karyotype.

Adenocarcinoma↗

Cell cycle perturbations in heterotransplanted squamous-cell carcinoma of the head and neck after mitomycin C and cisplatin treatment.

Cell kinetic studies are of interest for clarifying the concepts of chemotherapeutic strategy in the multimodality therapy of advanced squamous-cell carcinoma of the head and neck. A poorly-differentiated squamous-cell carcinoma of the head and neck heterotransplanted to nude mice was used for analyses of chemotherapeutically induced cell cycle perturbations. The heterotransplanted tumour, in its 15th or later passages in nude mice, was treated with either Mitomycin C or cisplatin. After determination of dose-response relationships and toxicity, treated tumours were biopsied at different times and cell cycle distribution pattern, 3HTdR incorporation into DNA, histology and tumour volume were recorded. Mitomycin C and cisplatin gave the same pattern of cell cycle perturbations, although the changes induced by cisplatin were more profound. There was an initial increase of the fraction of cells in the S phase, concomitant with a reduction of the fraction of cells in G0 + G1 phase. When these perturbations were normalized a transient increase of the fraction of cells in G2 + M phase was observed. However, while cisplatin caused an initial transient depression of DNA synthesis, the Mitomycin-C-treated tumours exhibited a short-lasting increase of DNA-synthesis. The maxima of the induced changes in cell cycle phase distribution and DNA-synthesis lasted for only 24-48 h, which may be of importance for scheduling combinations of drugs. Though both drugs induced profound changes in tumour volume growth and cell kinetics, there was no change in the histopathological picture of the treated tumours. Routine histopathological examination is thus not likely to be of value evaluating the effect of chemotherapy.

Animals↗