Search PubMed⌕ Search

Biomedical subjects

A Fischer

Publications and source records attributed to A Fischer.

At least 433 records · Page 24Linked to original sources

Sympathoadrenal progenitors in embryonic chick sympathetic ganglia show distinct responses to glucocorticoid hormones.

The sympathoadrenal cell lineage originates from the neural crest and comprises the neurons of sympathetic ganglia, adrenal and extra-adrenal chromaffin cells, and the so-called small intensely fluorescent cells. In vitro studies using mammalian immature chromaffin cells, adrenal or sympathetic ganglionic progenitors, or ganglionic small intensely fluorescent cells, have suggested that glucocorticoid hormones are essential for inhibiting neuronal differentiation of sympathoadrenal progenitors and promoting the chromaffin cell phenotype. In avian systems, however, the distinct cellular phenotypes in this lineage and the molecular cues underlying their differentiation have not been fully explored. In the chick embryo, early sympathetic ganglion anlagen are populated by granule-containing cells that morphologically resemble small intensely fluorescent cells and chromaffin cell progenitors. These cells subsequently disappear from the ganglia, by death and by transition into fully differentiated sympathetic neurons, as indicated by the appearance of cells that are ultrastructurally intermediate between granule-containing cells and fully differentiated neurons (granule-containing cells in transition). In the present study, we show that treatment of cultured sympathetic cells dissociated from embryonic day (E) 7, 9, or 11 lumbar sympathetic ganglia with the glucocorticoid hormones hydrocortisone or corticosterone has neither an inhibitory nor an inductive effect on phenotypes of granule-containing cells or granule-containing cells in transition. In cell cultures of E15 ganglia, however, glucocorticoid treatment induces a granule-containing cell resembling the granule-containing phenotype. These results suggest that the early granule-containing cells and granule-containing cells in transition in chick sympathetic ganglia are not the counterparts of glucocorticoid-responsive mammalian small intensely fluorescent or chromaffin progenitor cells, despite their morphological similarity. However, E15 sympathetic ganglia apparently contain a glucocorticoid-responsive progenitor population that can differentiate into chromaffin-like cells. These progenitors seem to require a systemic or intraganglionic developmental signal or undergo a temporal switch that renders them susceptible to glucocorticoids.

Adrenal Medulla↗

Further evidence that tachykinin-induced contraction of human isolated bronchus is mediated only by NK2-receptors.

The tachykinin-receptors mediating contraction of human bronchus have been characterized using both tachykinin-receptor selective agonists and blocking drugs under conditions where tachykinin metabolism by endogenous peptidases has been controlled, and true equilibrium conditions have been established. The findings that neurokinin A (EC50 = 2 nM) is the most potent agonist, and the NK2-receptor selective agonist, GR64349, is only 3-fold weaker, whereas agonists selective for NK1-receptors, substance P methyl ester, or NK3-receptors, senktide, are inactive, suggest that this effect is mediated exclusively by NK2-receptors. This is supported by observations that GR64349 is antagonised by the selective NK2-receptor blocking drugs, MEN10207 (pA2 = 6.7), R396 (pA2 = 6.1), (+/-)SR48968 (pA2 = 8.4) and GR159897 (pA2 = 8.6), but not by the NK1-receptor blocking drug, GR82334 (pA2 < 5). In approximately half of the preparations, the peptidase inhibitors, phosphoramidon (1 microM) and bestatin (100 microM), caused a marked and well-maintained contraction (approximately 20% of neurokinin A maximum), which may indicate a role for endogenous tachykinins in the regulation of tone in this preparation. This is supported by the finding that neurokinin A-immunoreactive nerve fibres are located around intrinsic neurones of local ganglia and within the smooth muscle layer of this preparation.

Aged↗

[Neonatal acute leukemia: apropos of 7 cases].

BACKGROUND: Acute leukemia in neonates is rare and is more severe than leukemia in childhood. POPULATION: Seven cases (four girls, three boys) were included in this series. Leukemia was diagnosed at birth in three cases; hepatosplenomegaly was seen in five cases and skin nodules in three. Hyperleukocytosis more than 100,000/mm3 was present in four cases; the WBC and differential counts were normal in two. A meningeal involvement was seen in one case. The leukemia was lymphoblastic (ALL) in three cases and myeloblastic (AML) in four. Intensive chemotherapy induced complete remission in five patients, persisting 5 and 4 years after the diagnosis in two. Classic risk factors such as high white blood counts, central nervous system involvement, myeloblastic lineage, absence of CALLA (common acute lymphoblastic leukemia antigen) expression and abnormal blast cell karyotype interesting the 11q23 area were found again in this series. Risk related to drug toxicities and infectious complications were also noted in this series of very young patients. CONCLUSIONS: The outcome may depend on progress in pharmacology, search for new drugs and use of bone marrow transplantation.

Female↗

Treatment of Omenn syndrome by bone marrow transplantation.

We report the outcome of allogeneic bone marrow transplantation (BMT) in nine consecutive patients with Omenn syndrome treated between 1980 and 1989. Five patients received unmanipulated marrow from a related matched donor, and four received T cell-depleted marrow from a haploidentical donor. The patients were conditioned with cyclophosphamide (200 mg/kg) and, except in one case, busulfan (16 mg/kg). Antithymocyte globulin and etoposide were given to three patients each; three recipients of T cell-depleted haploidentical marrow also received intravenous injections of an anti-leukocyte function-associated antigen type 1 antibody as graft rejection prophylaxis. All the patients were fed parenterally for 1 to 5 months before BMT to improve nutritional status and received topical corticosteroids (n = 8), systemic steroids (n = 2), etoposide (n = 1), or cyclosporine (n = 1) to control T-cell activation. Engraftment occurred in four of five recipients of human leukocyte antigen (HLA)-identical marrow and three of four recipients of HLA-haploidentical marrow. One patient died with cytomegalovirus infection. The other six patients are alive 4 to 11 years after BMT, with full chimerism in all but one case. Chronic graft-versus-host disease persists in one patient; the other five survivors have fully restored immune function and have no manifestations of Omenn syndrome, including failure to thrive. We conclude that both HLA-identical and haploidentical BMT can cure Omenn syndrome, provided that parenteral nutrition and immunosuppressive therapy are given before transplantation.

Bone Marrow Transplantation↗

Diurnal variation of urinary leukotriene E4 and histamine excretion rates in normal subjects and patients with mild-to-moderate asthma.

BACKGROUND: Leukotriene E4 (LTE4) and histamine excreted into the urine reflect the in vivo synthesis and release of cysteinyl leukotrienes and histamine, respectively. We examined the diurnal variation of the excretion rate of these mediators over 4 consecutive days in normal subjects (n = 5) and patients with stable mild-to-moderate asthma (n = 8). METHODS: Sixteen consecutive 6-hour urine samples were collected over 4 days. Urinary LTE4 concentrations were determined by reverse-phase high-pressure liquid chromatography, followed by ELISA. Urinary histamine concentrations were measured by ELISA. The excretion rates of these compounds were normalized relative to urinary creatinine content. RESULTS: The mean urinary LTE4 excretion rate was 83.8 +/- 38.2 pg/mg creatinine (mean +/- SD) in normal subjects; in patients with asthma, the urinary LTE4 excretion rate (110.0 +/- 59.2 pg/mg creatinine) was significantly higher than that in normal subjects (p < 0.05). The urinary histamine excretion rate was not different between normal subjects (24.0 +/- 12.5 ng/mg creatinine) and patients with asthma (31.5 +/- 25.8 ng/mg creatinine). A robust and systematic within-day variation (p < 0.01), but no day-to-day variation, was observed in histamine excretion rate. Although the magnitude of variation in LTE4 excretion within a day was significantly greater in patients with asthma than in normal subjects (p < 0.05), we could not identify any specific diurnal variation pattern in either the normal or the asthma group. No significant correlation was observed between urinary LTE4 and histamine excretion rate within any subject. CONCLUSIONS: Patients with asthma excrete LTE4 in the urine at a greater rate than normal subjects. Although no systematic variation in urinary LTE4 excretion rates over the course of a day was observed in either normal subjects or patients with stable asthma, the presence of a systematic diurnal variation of urinary histamine excretion exists in both groups.

Adult↗

Incidence of deep and superficial sternal infection after open heart surgery. A ten years retrospective study from 1981 to 1991.

Between January 1981 and December 1991, 4137 adult patients underwent various cardiac procedures via a median sternotomy under cardiopulmonary bypass. The overall infection rate was 1.33%, including superficial wound infections (SWI) (1.18%) and deep sternal infection (DSI) (0.145%). Pericardial and retrosternal suction drains with a vent allowed a better drainage of blood and serosities and probably contributed to our low DSI rate. Eleven factors predisposing to infection were evaluated by Fisher's exact test. Only the operative urgency (P = 0.006), reexploration for bleeding (P = 0.00001) and preoperative renal failure (P = 0.0005) were statistically significant. Twenty of our infected patients had no risk factors for infection. When the risk factors described in the literature were applied to our infected patients, only one had no risk factor.

Adolescent↗

Long-lasting exocytosis and massive structural reorganisation in the egg periphery during cortical reaction in Platynereis dumerilii (Annelida, Polychaeta).

The course of the cortical reaction in the Platynereis dumerilii egg is described from live observation and from sectioned fixed material and is found to differ in several aspects from the course of cortical reactions in better-known systems. Cortical granules are unusually numerous. They are discharged by exocytosis during a period of about 25 min following fertilisation (18 degrees C). Most of the surplus membrane material brought to the egg surface by exocytosis is set free into the perivitelline space. Swelling of egg jelly precursor secreted by cortical granule exocytosis may be causal for the detachment of the vitelline envelope from the egg cell surface which, however, remains attached punctately to the vitelline envelope by about 30,000 microvilli. Under the strain of the distending vitelline envelope, the bases of the microvilli move and line up, pulling the cell surface into a network of ridges. The grooves in between the ridges are the sites of exocytoses. Cytochalasin B, generally destabilising actin filaments, induces rupture of the microvilli and exaggerated distension of the vitelline envelope during the cortical reaction. In a final phase of the cortical reaction the vitelline envelope wrinkles and falls back onto the egg cell surface, the microvilli shorten and the egg cell transiently becomes deformed by local contractions. The cortical reaction in the nereid egg is discussed as a process of distortion and reorganisation of the egg cortex and plasmalemma. The abundance of cortical granules accommodating egg jelly precursor in the Platynereis oocyte is attributed to the mode of so-called diffuse oogenesis characteristic of nereids, i.e. of differentiation of oocytes freely suspended in the coelomic fluid. In nereids, egg jelly therefore forms after fertilisation as opposed to ovulation.

Animals↗

[Immunohistochemical studies of the neuroanatomy of the human turbinates: innervation pattern of seromucous glands].

Seromucous glands are among the main components of human nasal mucosa. To control the different physiological functions of these glands, a dense nerval network is necessary. The aim of this study was to demonstrate the general innervation of the seromucous glands in nasal mucosa. Tissue samples of inferior human turbinates were fixed and embedded in paraffin wax or frozen. Serial sections were performed and incubated with antibodies either to neuron-specific enolase (NSE) or S-100 protein. The ABC method was employed to demonstrate the immunacomplexes. The sections were counterstained with haemotoxylin. Either NSE and S-100 protein-immunoreactive nerve fibres were found around the acini, ducts and in the connective tissue of the glands. Furthermore, a dense network of fine nerve fibres was detected in the submucosal region. The localisation of neurons in nasal glands confirms the direct nerval control of the diverse glandular functions. Additionally, the sensitive subepithelial network of fine nerve fibres might be involved in the regulation of glandular secretion.

Adult↗

[Current immunohistochemical results of localization of vasoactive intestinal polypeptide (VIP) in nasal mucosa of the human].

Besides classic neurotransmitters, neuropeptides seem to participate in the control of human nasal physiology. In this region vasoactive intestinal peptide (VIP) is found in higher concentration than other neuropeptides. The aim of this study was to localize VIP in neuronal and non-neuronal structures of the human nasal mucosa using immunocytochemical techniques. Paraffin and frozen serial sections of the inferior turbinate were incubated with antibodies against neuronspecific enolase (NSE) to demonstrate neuronal structures or against VIP. The immunocomplexes were visualized by the Avidin-Biotin-Complex (ABC)-method. VIP-positive nerve fibers were found around the acinus cells and the ducts of the seromucous glands. These results emphasize the influence of VIP on nasal gland secretion. Few immunoreactions to the VIP were demonstrated in the nerves of the adventitia of veins and arteries. Additionally, by comparing NSE nad VIP localization, strong extranerval immunoreactions in the tunica medica of the arterioles were demonstrated, as were lesser but still visible immunoreactions in the muscular layer of thick veins. These morphological findings in vessels and the well known vasodilatory effect of VIP underline the functions of this neuropeptide on the nasal mucosa in man. Thus, by increasing the blood flow and volume, VIP, in conjunction with other control factors, seems to participate in the physiological processes of the swelling mechanism of nasal turbinates and influence nasal congestion.

Adult↗

DNA-based mutation analysis of Bruton's tyrosine kinase gene in patients with X-linked agammaglobulinaemia.

The identification of the BTK (Bruton's tyrosine kinase) gene defective in human immunoglobulin deficiency X-linked agammaglobulinaemia (XLA) and characterisation of BTK exon-intron boundaries has now allowed the analysis of mutations and polymorphisms at the level of genomic DNA. Using Southern blot analysis and the polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) assay, amplifying all 19 exons and the putative promoter region with a single annealling temperature, mutations have been identified in 19 out of 24 unrelated patients diagnosed as having XLA. Apart from a large deletion involving exon 19, nine missense (F25S, R288W, 1370M, M509V, R525P, N526K, R562W, A582V and G594R), two nonsense (E277X and R525X), five frameshift and two splice site mutations have been found affecting most coding exons and all major enzyme domains. No mutations or polymorphisms were detected in the putative promoter region. A single nucleotide deletion located in the last exon, resulting in a truncation of the eight C-terminal residues of Btk and a typical XLA phenotype, indicates structural and/or functional importance of Btk helix I in the catalytic domain. Although allelic heterogeneity at the BTK locus may partly explain clinical variability in families with XLA, compensatory and redundant mechanisms involved in B-cell development must play a role in the phenotypic diversity of the disease.

Adolescent↗

The chronically symptomatic vulva: aetiology and management.

OBJECTIVE: To determine the causes and management of chronic vulval symptoms and to compare the findings in patients first presenting to a gynaecologist with those in patients first presenting to a dermatologist. DESIGN: A prospective study of 144 patients, approximately half each being referred to a gynaecologist and a dermatologist. Diagnosis was based on clinical history, vulvoscopy, vulval biopsy and bacteriology. Biopsies were examined by a histopathologist experienced in dermatopathology and gynaecological pathology. RESULTS: The two patient groups were similar in both range and frequency of conditions. The commonest cause of chronic vulval symptoms was dermatitis, which was found in 64% of our patients. Dermatitis occurred alone in 55% and was found in association with histological evidence of human papilloma virus (HPV) in a further 9%. These patients responded to simple dermatological methods, mainly topical corticosteroids. Histopathological evidence of HPV was encountered in only 23% of our patients, and of these 36% also demonstrated dermatitis on biopsy. Most responded to topical corticosteroids. Another 7% had lichen sclerosus, and all responded to potent topical corticosteroid. The remaining 15% demonstrated a range of diagnoses, including psoriasis, dysaesthetic vulvodynia, vulval intraepithelial neoplasia (VIN) and chronic candidiasis. The majority of patients had a corticosteroid responsive dermatosis rather than a gynaecological condition. CONCLUSIONS: The majority of patients with a chronically symptomatic vulva who present to either a gynaecologist or a dermatologist have a dermatological condition that responds to simple dermatological treatments. We believe that the presence or absence of the human papilloma virus is not relevant to most patients with a chronically symptomatic vulva and treatments should not be aimed at eradicating this virus. Histopathologists and gynaecologists who have focused on gynaecological disorders have often missed simple dermatological conditions that are easily treatable.

Adolescent↗

[Is co-administration of ethanol to the distension medium in surgical hysteroscopy a screening method to prevent fluid overload? A prospective randomized comparative study of ablative versus non-ablative hysteroscopy and various ethanol concentrations].

OBJECTIVE: Is it possible to diagnose early a beginning fluid absorption during operative hysteroscopy by adding ethanol to the distension medium? METHODS: A prospectively randomised comparative study of ablative versus non-ablative operative hysteroscopy with differing ethanol concentration was performed. Purisole (a mannitol/sorbitol solution) was used as distension medium. RESULTS: The results of the study show that at those hysteroscopical procedures at which the endometrium is not or only minimally injured (e.g. syneciolysis, hysteroscopic proximal tubal catheterisation) an intraoperative screening is not necessary due to the low absorbing amounts. At the hysteroscopical procedures as the resection of myoma, endometriumablation and septumresection, however, an addition of ethanol of 2% to the distension medium has proved to be useful, because with this method absorbing amounts from 400 mls can be established by positive values of breath alcohol. As the result of a further absorption of fluid, but delayed in time compared to the first positive value of breath alcohol, there is an increase of the central venous pressure and a hyponatraemia. CONCLUSION: The intraoperative ethanol-monitoring is a non-invasive procedure which can be performed at ablative-operative hysteroscopies and has no negative influence on the course of the intervention and the general condition of the patients.

Adult↗

Lymphoproliferative disorders after organ transplantation: a report of 24 cases observed in a single center.

PURPOSE: Organ recipients are at a high risk of post-transplant lymphoproliferative disorders (PTLDs) as a complication of immunosuppressive therapy. We report the incidence, clinical presentation, pathologic findings, treatment, and outcome for 24 cases of PTLD observed at our institution. PATIENTS AND METHODS: Twenty-four (1.7%) of 1,385 organ transplant recipients developed PTLDs. Dosages of immunosuppressive drugs were reduced in 19 patients. Treatment consisted of anti-B-cell monoclonal antibodies (12 patients), and/or chemotherapy (eight patients), or surgery (two patients). RESULTS: The median time between grafting and the onset of PTLD was 210 days. Tumors were classified as monomorphic and polymorphic in nine and 15 cases, respectively. Three of 24 cases were of T-cell origin. Genotypic studies confirmed the monoclonality of the tumors in 11 cases among 14 PTLDs tested. Epstein-Barr virus (EBV) infection was associated with 70% of B-cell PTLDs tested. The overall survival duration was 5 months. Ten patients are alive and disease-free with a median follow-up time of 37 months; most were treated with anti-B-cell antibodies. Two other patients died in complete remission of unrelated causes at 33 and 38 months. CONCLUSION: Anti-B-cell monoclonal antibody therapy seems to be effective in PTLD, even in monoclonal B-cell forms, but other approaches will be necessary to improve survival further.

Adolescent↗