Fluoride-resistant acid phosphatase-containing neurones in dorsal root ganglia are separate from those containing substance P or somatostatin

The distribution of fluoride-resistant acid phosphatase, substance P and somatostatin were investigated in the dorsal horn of the spinal cord and in dorsal root ganglia. In the dorsal horn, the distribution of fluoride-resistant acid phosphatase closely paralleled that of somatostatin and only partly overlapped with that of substance P. In sensory ganglia, none of the fluoride-resistant acid phosphatase-containing neurones contained either substance P or somatostatin. The results suggest the existence of a population of fluoride-resistant phosphatase-positive sensory neurones which is distinct from neurones containing either of these peptides.     

Dynamic balance of metabotropic inputs causes dorsal horn neurons to switch functional states

Sensory relay structures in the spinal cord dorsal horn are now thought to be active processing structures that function before supraspinal sensory integration. Dorsal horn neurons directly receive nociceptive (pain) signals from the periphery, express a high degree of functional plasticity and are involved in long-term sensitization and chronic pain. We show here that deep dorsal horn neurons (DHNs) in Wistar rats can switch their intrinsic firing properties from tonic to plateau or endogenous bursting patterns, depending upon the balance of control by metabotropic glutamate (mGlu) and GABA(B) receptors. We further show that this modulation acts on at least one common target, the inwardly rectifying potassium channel (Kir3). Finally, we found that these firing modes correspond to specific functional states of information transfer in which dorsal horn neurons can faithfully transmit, greatly enhance or block the transfer of nociceptive information.     

Biochemistry of chronic jejunal ulcer in patients

Separation and measurement of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenine-adenosine, lipid phosphates (lipid P), ribonucleic acid (RNA), deoxyribonucleic acid (DNA), further of Mg2+-dependent, total (Mg2+-dependent plus Na+-K+-dependent) and Na+-K+-dependent ATPases was carried out in control (non-ulcerated) and ulcerated (mucosa up to 2.0 cm around the ulcer) jejunal mucosa of 11 patients with chronic jejunal ulcer, who had undergone a Billroth II gastric resection for duodenal ulcer. The levels of ATP, ADP, AMP, sum of ATP + ADP + AMP, lipid-P, RNA (related to 1.0 mg DNA) and the activity of Mg2+-dependent, total (Mg2+-dependent plus Na+-K+-dependent) and Na+-K+-dependent ATPase (related to 1.0 mg membrane protein) were significantly higher in the lacerated jejunal mucosa than in the control one. The results indicate that (1) no circulatory damage can be found in the ulcerated jejunal mucosa; (2) a cellular hyperactivity (increased ATP breakdown and increased ATP resynthesis, increased RNA and lipid synthesis) occurs in the ulcerated jejunal mucosa; (3) the biochemical structure of cells differs significantly in the control and the ulcerated jejunal mucosa.     

Presence of parvoviruses in the intestine of chickens showing stunting syndrome

Small viral particles of 19 to 24 nm in diameter with a buoyant density in CsCl of 1.43 g/ml were detected electron microscopically in samples taken from the gut of 10-day-old chickens suffering from a stunting syndrome. The viral particles are suggested to belong to the Parvoviridae and their possible role in the stunting syndrome is discussed.     

Complementation of class II A alleles in the immune response to (GluLysTyr) polymers

The proliferative T cell responses to poly(GluLysTyr) (GLT) and poly(GLULysPhe) (GLPhe) are restricted by the E alpha E beta class II MHC molecule (E) in most responded strains. Some nonresponder strains that carry responder E beta, but cannot express cell surface E molecules, can complement with other nonresponder strains that provide the missing E alpha chain needed for the expression of E molecules and for responsiveness to GLT and GLPhe. Here another type of complementation is described between two E-nonexpressor haplotypes, H-2f and H-2s, which result in E-nonexpressor F1 hybrids, which are responders to GLT. The restriction element involved in this response is an Af/As hybrid molecule. The data support the hypothesis that conformational determinants resulting from the free association of alpha and beta chains in heterozygotes can increase the immune potential of the individual.     

Biochemistry of antral ulcer in patients

Separation and measurement of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), adenine-adenosine, lipid phosphates (lipid-P), RNA and DNA, furthermore, separation of Mg2+-dependent, total (Mg2+-dependent plus Na+--K+-dependent or Mg2+--Na+--K+-dependent) and Na+--K+-dependent ATPases and measured of their activities were carried out in tissue samples obtained from "ulcerated antral mucosa", from "non-ulcerated antral mucosa" and the muscular layer beneath the examined mucosa specimens, of patients with antral ulcer. It has been found that (1) the tissue levels of ATP, ADP and AMP, of the sum ATP + ADP + AMP, adenine-adenosine, lipid-P, RNA all calculated for 1.0 mg DNA content, further, the activities of Mg2+-dependent, total (Mg2+-dependent plus Na+--K+-dependent) and Na+--K+-dependent ATPase were significantly higher in the ulcerated antral mucosa than those in the control antral mucosa; (2) no significant biochemical alterations were found in the muscles under the ulcerated and non-ulcerated antral mucosa of patients with antral ulcer; (3) the extents of increases in the substrate levels of ulcerated antral mucosa depended on their original levels in the control antral mucosa. The results indicate a cellular hyperfunction in the ulcerated antral mucosa, in comparison with the control one. No circulatory injury could be demonstrated in the ulcerated antral mucosa.     

A second field metachronous Merkel cell carcinoma of the lip and the palatine tonsil confirmed by microarray-based comparative genomic hybridisation

Merkel cell carcinoma was diagnosed in a 79-year-old Caucasian woman. The tumour was localised to the upper lip and was in stage T2. After successful cryosurgery and a 7-year tumour-free period, a new tumour developed in her palatine tonsil. Histologically and immunohistochemically, this resembled the tumour in the lip. The regional lymph nodes were devoid of metastasis. The paraffin-embedded material of the two tumours and the unaffected lymphatic tissue were analysed with DNA microarrays for comparative genomic hybridisation to assess the genetic relationship of the tumours. In both tumours, regions on 2p and 10p were commonly over-represented, while 41 regions on chromosomes 1–4, 6, 8–9, 11 and 14–22 were commonly under-represented. Chromosomes 1, 3, 4, 16–18 and X were most frequently involved in the DNA losses. In gene copy numbers in the two tumours, 31 chromosome locations were found to be differently affected. The partly similar and partly different molecular patterns indicated a genetic relationship between the tumours and excluded the possibility that the tonsillar tumour was a metastasis. The findings suggest that a genetically altered field was the reason for the development of the tonsillar cancer; thus, it can be regarded pathogenetically as a second field tumour.     

Inflammatory mediators convert anandamide into a potent activator of the vanilloid type 1 transient receptor potential receptor in nociceptive primary sensory neurons

The endogenous ligand, anandamide activates at least two receptors on nociceptors; the excitatory vanilloid type 1 transient receptor potential receptor, the activity of which is indispensable for the development and maintenance of inflammatory heat hyperalgesia, and the inhibitory cannabinoid 1 receptor, the activity of which reduces that pathological pain sensation. Recent data are equivocal on whether increasing anandamide levels at the peripheral terminals of nociceptors in pathological conditions increases or decreases inflammatory heat hyperalgesia. Here, by using the cobalt-uptake technique we examined whether vanilloid type 1 transient receptor potential receptor activity evoked by 10 nM-100 microM anandamide is increased or decreased in inflammatory conditions. An inflammatory milieu for cultured rat primary sensory neurons was established by incubating the cells in the presence of the inflammatory mediators, bradykinin and prostaglandin E2. Anandamide, similarly to the archetypical vanilloid type 1 transient receptor potential receptor agonist, capsaicin induced concentration-dependent cobalt-uptake in a proportion of neurons. However, the potency of anandamide was significantly lower than that of capsaicin. While pre-incubation of cultures with bradykinin and prostaglandin E2 alone did not evoke cobalt-entry, the inflammatory mediators potentiated the effect of both capsaicin and anandamide. Application of the competitive vanilloid type 1 transient receptor potential receptor antagonist, capsazepine, or inhibitors of protein kinase A, protein kinase C or phospholipase C inhibited the anandamide-evoked cobalt-uptake both in the presence and absence of bradykinin and prostaglandin E2. These findings show that inflammatory mediators significantly increase the excitatory potency and efficacy of anandamide on vanilloid type 1 transient receptor potential receptor, thus, increasing the anandamide concentration in, or around the peripheral terminals of nociceptors might rather evoke than decrease inflammatory heat hyperalgesia.     

Influence of Dialysable Transfer Factor on IgE Concentrations in Patients with Atopic Dermatitis

Dialysable transfer factor (TF) was given in 10 paediatric patients with severe atopic dermatitis (AD). Ten patients with AD, matched for age and severity of disease, served as controls.
Prior to the therapy with TF and at weekly intervals thereafter, T- and B-cells in the blood, PHA-stimulation, total IgE and specific IgE antibodies to inhalant and food antigens were determined. Therapy with TF was followed by IgE depression in 8/10 patients and was most pronounced in three patients with initially high levels. Some decrease of IgE levels was seen in four controls also, none of them, however, fell to normal levels as was seen in two of the treated patients.
Specific IgE levels decreased slightly, but always remained within the pathological range. T-cell counts in the blood increased in 2/10 cases as well as PHA-stimulation. B-cell counts remained within normal limits. Clinical improvement was seen in one patient, five improved slightly and four remained unchanged.
Our results indicate, that transfer factor can lower total IgE levels in cases with atopic dermatis. The effect is most marked in patients with high total IgE levels. Skin involvement, however, does not closely follow in vitro findings.     

Intracellular signalling and cytoskeletal rearrangement involved in Yersinia pestis plasminogen activator (Pla) mediated HeLa cell invasion

Yersinia pestis, the etiologic agent of plague is a highly invasive organism being able to invade non-phagocytic epithelial cells. Its plasminogen activator (Pla), encoded by the pPCP1 plasmid plays a pivotal role in internalisation of bacteria by HeLa cells. The aim of this study was to analyse the intracellular signalling processes and cytoskeletal rearrangement events associated with invasion. Wortmannin caused a 50% decrease of invasiveness at 50nM concentration pointing to the involvement of phosphatidyl-inosinol-4 kinase (PtINs4). Pre-treatment with staurosporin, a potent inhibitor of protein kinases (PKs) and with genistein, a specific tyrosine kinase inhibitor decreased the number of internalised bacteria about seven-fold and two-fold, respectively, indicating the involvement of PKs including tyrosine kinases in Pla-mediated internalisation. Cytochalasin D, an actin polymerisation inhibitor, C3 exoenzyme of Clostridium botulinum, a specific inhibitor of small GTPase Rho, and NDGA, a 5-lipoxygenase inhibitor also involved in Rho activation strongly reduced the number of internalised bacteria revealing the role of cytoskeletal events in the invasion process. All the tested inhibitors changed the invasion but not the adhesion pattern of the Pla producing recombinant strain. Actin rearrangement could also be visualised also with rhodamin-phalloidin staining.