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Biomedical subjects

O Johansson

Publications and source records attributed to O Johansson.

At least 73 records · Page 4Linked to original sources
PubMed1995

High allele loss rates at 17q12-q21 in breast and ovarian tumors from BRCAl-linked families. The Breast Cancer Linkage Consortium.

Loss of heterozygosity (LOH) was evaluated in 174 breast and ovarian tumors derived from 94 families with at least 3 first-degree relatives affected with either of these cancers. By linkage analysis 26 families were identified as having a high posterior probability of being due to BRCAl (the breast/ovarian cancer susceptibility locus on 17q12-21) with lod scores varying from 0.51 to 9.49. Tumor genotypes were determined at at least 2 constitutionally heterozygous markers flanking BRCAl in a total of 58 tumors from these families. These tumors were derived from 52 patients, the BRCAl mutation carrier status of which was evidenced by DNA sequencing in 20, and inferred by reconstructing haplotypes in the remainder. LOH was detected in 50 (86%) tumors, and invariably involved the wild-type allele. Where informative, this allele was of paternal origin in 33 cases and of maternal origin in 10 cases. These results strongly suggest that BRCAl is a tumor suppressor gene and that LOH is greatly favored to fully inactivate it.

Alleles↗
PubMed1995

The central nervous system of Grillotia erinaceus (Cestoda: Trypanorhyncha) as revealed by immunocytochemistry and neural tracing.

Immunofluorescent labeling and neural tracing techniques were employed in conjunction with confocal scanning laser microscopy to study the intact neuroanatomy of the central nervous system of the trypanorhynch tapeworm Grillotia erinaceus. Immunocytochemical labeling for the general nerve fibre marker PGP 9.5 showed a pattern of extensive labeling that paralleled findings obtained with the neural tracer DiI. In contrast, immunocytochemical labeling for 5-hydroxytryptamine (5-HT) was localised to cell bodies lying on the periphery of the ganglion, with fine immunoreactive fibres radiating out towards the bothridia. Following the retrograde transport of the fluorescent molecule DiI through axotomised nerve cords, it successfully labeled both the cerebral ganglion and associated nerve fibres within the scolex. The cerebral ganglion was shown to give rise to posterior nerve cords, an array of radial fibres that pass out to the bothridia, and to contain a centrally disposed group of cell bodies thought to be involved in efferent functions.

Animals↗
PubMed1995

Distribution and chromatographic analysis of galanin immunoreactivity in the heart.

The presence and distribution of the biologically active neuropeptide galanin (GAL), in the rat heart as well as in mouse, guinea pig, rabbit, cat, and dog heart, were analyzed. With some minor variations in the overall distribution, extractable GAL-like immunoreactivity (-LI) was present in all major portions of the heart. In the rat heart, GAL-immunoreactive (GAL-IR) nerve fibers were present in the atria as well as in the ventricles; thin GAL-IR fibers were present in the myocardium as well as around some cardiac blood vessels. A few larger GAL-IR nerve fiber bundles were also present on the surface of the heart. Characterization of extractable GAL-LI in the rat heart, using HPLC, revealed one GAL-IR form, coeluting with synthetic rat GAL. Our findings suggest that galanin is of importance in the control of certain cardiac functions and/or of circulation.

Animals↗
PubMed1995

Rearrangement of S-100 immunoreactive Langerhans' cells in human psoriatic skin treated with peptide T.

Dendritic cells marked by protein S-100 (S-100) antiserum in the suprabasal layers of the epidermis have previously been identified to be Langerhans' cells. In this study, S-100 immunoreactive cells have been investigated in psoriatic lesioned skin during and after peptide T treatment. Peptide T is an octapeptide with affinity for the CD4 receptor. Nine patients were intravenously infused with peptide T, 2 mg in 500 ml saline per day for 28 days. Sections from involved skin before, every week during, and after the treatment were processed by indirect immunofluorescence using S-100 antiserum. Before the treatment the epidermal Langerhans' cells were numerically decreased or even completely gone in the involved skin of psoriasis as compared to skin from normal healthy controls, while the dermal dendritic cells instead were increased and gathered in cell clusters around vascular structures. Four of the nine patients had histopathological improvements after the peptide T treatment, and, in those cases, the dendritic cells in the dermis were reduced in number, and the Langerhans' cells in the epidermis were numerically increased as well as even reversed to normal position and morphology. These changes in the distribution and density of Langerhans' cells represent their rearrangement during the course of psoriasis and/or the remission after peptide T treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Immunohistochemical evidence of alpha-, beta- and gamma 3-melanocyte stimulating hormone expression in cutaneous malignant melanoma of nodular type.

Opiomelanocortins are formed after cleavage of the larger precursor molecule, proopiomelanocortin (POMC), which contains several peptide residues, sharing certain amino acid homology, including adrenocorticotrophic hormone (ACTH) and alpha-, beta- and gamma-melanocyte stimulating hormone (MSH). The expressions of alpha-, beta- and gamma 3-MSH in human cutaneous malignant melanoma of nodular type are demonstrated. For the MSHs, the immunolabelling was concentrated mostly in the tumour cellular cytoplasm, with occasional cells displaying a nuclear staining. Labelled tumour cells were dispersed throughout the epidermis and dermis as individual cells or in so-called 'pearl-like nests', most of which consisted mainly of round or oval shaped cells as well as a few pleomorphic or spindle-shaped cells. The fluorescence intensity seemed to increase in accordance with the development of the tumours. All cases examined were clearly stained with protein S-100, which provided us with a definite diagnosis. Considering the overall MSHs-related staining intensity of each section, the general perception we got was that the closer to the centre of the tumour parenchyma, the stronger was the staining and, furthermore the larger/more poorly differentiated the cells, the stronger was the staining. We also found the MSHs expressions to appear in the peripheral part of the tumour and the perilesional tissues including epidermis, sweat glands, sebaceous glands as well as hair follicles. Neurohypertrophic features were encountered including increases in both the number of nerve fibres and their diameter. Our results presented here strongly support the viewpoint earlier proposed that MSH peptides, by an autocrine and/or paracrine production from melanoma cells, are engaged in the regulation of melanogenesis, growth and proliferation of the tumour cells. We also conclude that, although alpha-, beta- and gamma 3-MSH peptides do not provide as high a sensitivity for diagnosis as protein S-100, they appear as useful markers for supportive diagnosis and assessment of malignant melanoma.

Adult↗
PubMed1995

Ultrastructural evidence for nerve fibers within all vital layers of the human epidermis.

To prove the existence of human intraepidermal nerve fibers at the electron microscopic level, we used both conventional and immunohistochemical ultrastructural techniques. Specimens were obtained from skin of the back, one of the most densely innervated areas of the human epidermis. The immunohistochemical marker protein gene product 9.5 was chosen because it is highly potent in labeling nerves. Thin nerve fibers were found in the basal, spinous, and granular layers of the epidermis with both techniques used, although it was more difficult to identify the nervous structures with the conventional method. The nerves appeared in the intercellular spaces and contacted keratinocyte cell bodies or cilia by membrane-membrane apposition, but without any specialized structures. Nerve fibers in the very superficial part of the vital human epidermis have not been described before at the ultrastructural level.

Humans↗
PubMed1995

Neurochemical markers in human cutaneous Merkel cells. An immunohistochemical investigation.

Merkel cells (MCs) are specialized sensory cells widely distributed in the epithelia of vertebrates. A variable immunohistochemical pattern of neuronal and neurotransmitter markers has been demonstrated in MCs of several species including man. In the present study, we investigated the expression of neurochemical markers in a selected population of human cutaneous MCs by immunofluorescence. The structural neural proteins protein gene product 9.5 and neuron-specific enolase were found to be the most reliable markers for MC identification. Moreover, neurofilament immunoreactivity was shown in a small subset of epidermal MCs. Among the neurotransmitter markers, evidence for expression of calcitonin gene-related peptide, vasoactive intestinal polypeptide, peptide histidine isoleucine amide, neuropeptide Y, neurokinin A, galanin, substance P, somatostatin and phenylethanolamine N-methyltransferase was found. These immunoreactivities were highly variable as far as number of positive cells and staining intensity were concerned. The results indicate that a complex and heterogeneous immunophenotype can be expressed even within a homogeneous population of human MCs.

Adult↗
PubMed1995

Histaminergic nerves demonstrated in the skin. A new direct mode of neurogenic inflammation?

An intradermal administration of histamine into human skin results in a local erythema, edema and often also the sensations of itch and/or pain. These effects have classically been attributed to the presence of histamine-containing mast cells. However, in the present investigation, we report the observation of histamine-immunoreactive nerves in the skin of Sprague-Dawley rats using a new and highly sensitive immunohistochemical approach. These data suggest a more direct route of cutaneous histamine effects, mediated exclusively by the peripheral nervous system. The findings could also give a new basis for explaining histamine-related issues, such as itch.

Animals↗
PubMed1995

Innervation of the human vaginal mucosa as revealed by PGP 9.5 immunohistochemistry.

In order to obtain a description of the innervation of the vaginal wall we employed an antiserum against the general neuronal marker, protein gene product 9.5, on normal human vaginal mucosa. Specimens were taken from the anterior and posterior fornices, from the anterior vaginal wall at the bladder neck level and from the introitus vaginae region, and then processed for indirect immunohistochemistry. All regions studied revealed a profound innervation, although regional differences were noted. The more distal areas of the vaginal wall had more nerve fibers compared to the more proximal parts. Also, biopsies from the anterior wall generally were more densely innervated than the posterior wall. Some large nerve coils were observed in lamina propria of the anterior wall as well as gatherings of thick-walled medium-sized blood vessels. Free intraepithelial nerve endings were only detected in the introitus vaginae region. These fibers were very thin, always varicose and could be observed just a few cell layers from the surface. In this part of the vagina, protein gene product 9.5 antibodies also stained cells within the basal parts of the epithelium. These cells were also neurone-specific enolase positive and resembled, from a morphological point of view, Merkel cells.

Female↗
PubMed1995

Carboplatin in combination with epirubicin and cyclophosphamide in patients with advanced ovarian cancer. A phase II study.

Seventy-one patients with epithelial ovarian cancer stage III (n = 56) or IV (n = 15) were treated with carboplatin 300 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 400 mg/m2 every fourth week. Patients clinically free of tumour after six courses (n = 58) underwent a second-look laparotomy. Seventeen patients were microscopically tumour-free (24% of all) and an additional 10 (14%) had only microscopic cancer. Median time to progression was 19 months. The median survival was 33 months and the estimated 5-year survival 27%. The toxicity was mainly haematological, with leukopenia WHO grade 3-4 seen in 88% and thrombocytopenia grade 3-4 in 42% of the patients. The gastrointestinal toxicity was mild and no renal toxicity was seen. This chemotherapy regimen was effective with acceptable toxicity and could be given on an out-patient basis. The possibility of increasing the efficacy and decreasing the toxicity was discussed.

Adult↗
PubMed1995

Variations in epidermal thickness in expanded human breast skin.

Tissue expansion generates metabolic and morphological changes in the expanded tissues. The alteration of epidermal and dermal thickness has been investigated in many animal studies, but few human studies have been published. We have studied 11 women whose breasts were reconstructed with tissue expansion after mastectomy. The expanded breast skin was biopsied on three occasions: before expansion, at the time of maximal expansion, and six months after the completed reconstruction. Specimens were prepared for light microscopy and epidermal thickness was assessed. There was a significant increase in epidermal thickness (p < 0.05) at the time of maximal expansion. The values before and at six months after reconstruction were not significantly different from each other. We conclude that the epidermis increases in thickness as a result of expansion and returns to normal thickness six months after cessation of expansion.

Biopsy↗
PubMed1994

Distribution and chromatographic analysis of galanin message-associated peptide (GMAP)-like immunoreactivity in the rat.

Galanin message-associated peptide (GMAP) constitutes the C-terminal part of the precursor protein encoding also the biologically active neuropeptide galanin (GAL). We have raised antisera against a species-conserved portion of GMAP, and investigated the localization of GMAP-like immunoreactivity (-LI) in relation to that of GAL-LI in the rat central and peripheral nervous system using the indirect immunofluorescence technique. In the central nervous system, GMAP-immunoreactive (-IR) cell bodies were observed in the hypothalamus, while GMAP-IR nerve fibers were demonstrated in the septum, hypothalamus, pons and spinal cord. In the posterior pituitary and in the connecting infundibular stalk, weakly fluorescent GMAP-IR nerve fibers were observed. GMAP-IR nerve fibers were also observed throughout the gastrointestinal tract, i.e., from the stomach down to the colon, and in all layers, except in the epithelium, of the wall. In general, the staining of consecutive tissue sections suggested that GMAP-IR was co-distributed with that of GAL-IR. A sensitive radioimmunoassay (RIA) for characterization of GMAP-IR in the rat central and peripheral nervous system was also developed. Characterization of GMAP-LI in acid extracts of rat brain and small intestine, using reverse phase high pressure liquid chromatography (rpHPLC), revealed multiple GMAP-IR forms that co-eluted with a synthetic porcine GMAP(19-41)-amide fragment, or were less or more polar than this fragment. The corresponding chromatographic analysis of GAL-LI revealed only one major form corresponding to rat GAL. The immunohistochemical data indicate that a GMAP-like peptide(s) probably is axonally transported and may possibly have pre- and/or post-synaptic functions. The nature of the multiple GMAP-IR components remains to be investigated, but may tentatively represent differently processed and/or chemically modified forms of rat GMAP(1-60).

Amino Acid Sequence↗
PubMed1994

Histamine immunohistochemistry is superior to the conventional heparin-based routine staining methodology for investigations of human skin mast cells.

Conventional studies of mast cells are limited by methodological restrictions such as a selective fixative-dependent routine staining blockage. This is thought to depend on the biochemical differences of the mast cell granule contents suggesting a cellular heterogeneity. Investigations of human mast cells, using routine methods, also suffer from the problem of a low signal-to-noise ratio. In the present study, normal human skin was used to compare an immunohistochemical method for histamine with two recommended mast-cell fixatives and a new commercial fixative in combination with three routine stains. Mast cells were found throughout the dermis with all the routine stains used. However, immunohistochemistry gave profoundly better results. Small structures, such as thin cytoplasmatic extensions and single granules, were readily detectable. Double-staining (immunohistochemistry followed by routine staining) revealed differences in staining capacity. All immunoreactive cells were not stained by routine stains and sometimes the opposite was also seen. This supports earlier reported evidence of heterogeneity, not only between skin and intestinal mast cells but also among skin mast cells themselves. Furthermore, by focusing on histamine, instead of heparin, we probably overcame the problems of the selective fixative-dependent routine staining blockage. Finally, the immunofluorescence technique provides a high signal-to-noise ratio and is an excellent method for making high-quality microphotographs of human mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1994

Immunohistochemical studies of neurochemical markers in normal human buccal mucosa.

The content of various substances, such as regulatory peptides, hormones and structural proteins, was investigated in normal buccal mucosa using indirect immunofluorescence. Thin nerve fibres, which from a morphological point of view were most probably sensory, showed immunoreactivity for substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide K (NPK) and neurokinin A (NKA). Also galanin (GAL), gamma-melanocyte stimulating hormone (gamma-MSH) and somatostatin (SOM) stained thin fibres were found in the propria, which were, however, few in number and the gamma-MSH staining was weak. CGRP, vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine amide (PHI) and neuropeptide Y (NPY) immunoreactive nerve fibres were observed in close connection to blood vessels. SOM positive cells with processes were found, mostly scattered, in the connective tissue. A population of cells within the epithelium also showed somatostatin immunoreactivity. Protein S-100 (S-100) stained distinct populations of cells at two separate locations. In the propria, cells with one or two slender processes were seen, being mostly single but sometimes forming groups. In the epithelium, dendritic cells with many processes with or without 'spines' were observed, mainly located to the basal layer of the lamina epithelialis. Single nerve fibres and nerve bundles were also stained. Neurofilament (NF) positive fibres, singly and in bundles, as well as endorgan-like structures were seen. Neuron-specific enolase (NSE) and protein gene product 9.5 (PGP 9.5) both stained the same structures, namely single fibres, nerve bundles, nerves surrounding vessels and innervating muscles and glands (if present in the section), as well as Merkel cells. Also with these two markers endorgan-like structures were seen. No clear innervation of the epithelium could be observed with the markers used. No methionine-enkephalin (ENK) or synaptophysin (SYN) immunoreactive material was found.

Adolescent↗
PubMed1994

Microflora modulates endocrine cells in the gastrointestinal mucosa of the rat.

BACKGROUND/AIMS: Gastrointestinal peptides and biogenic monoamines participate in the regulation of gastrointestinal functions. The aim of this study was to examine the influence of the microflora on the distribution of endocrine cells and on the release of gastrointestinal peptides. METHODS: A quantitative morphological study using stereological methods was performed in gastrointestinal sections of conventional and germ-free rats. Tissue and plasma concentrations of peptides were measured. RESULTS: The total volumes of gastrin- and serotonin-immunoreactive cells were significantly increased in the gastric mucosa of germfree rats (P < 0.05), as well as the total volumes of serotonin- and motilin-immunoreactive cells in the ileum (P < 0.05) and serotonin-immunoreactive cells in the colonic mucosa (P < 0.05). The tissue concentration of somatostatin was significantly higher in the jejunum (P < 0.05) and lower in the ileum of germfree rats than in controls (P < 0.05). Plasma glucagon was significantly increased in germfree rats (P < 0.05). The total volume of the fundic mucosa was enlarged in germfree rats (P < 0.05), whereas the total volume, the mucosal thickness, and the number of crypt cells of the colonic mucosa were significantly reduced in these rats compared with controls (P < 0.05). CONCLUSIONS: Our findings suggest that the intraluminal microflora influences the release of biologically active peptides and that it participates in the regulation of gastrointestinal endocrine cells and the epithelial structure.

Animals↗