Thalidomide and recurrent aphthous stomatitis: a follow-up study

AIM: To investigate the effects of dipfluzine (Dip), a new derivative of cinnarizine (Cin), first developed by China, upon 5-hydroxytryptamine (5-HT)-induced contractions in cerebral arteries. METHODS: Compared Dip, flunarizine (Flu), and Cin antagonistic effects and actions on 2-component contractions evoked by 5-HT in isolated pig basilar artery. RESULTS: Dip showed a greater concentration-dependent antagonistic effect on 5-HT-evoked contraction than Cin and Flu in pig basilar artery rings. The order of potency (IC50) was Dip (4.0 mumol.L-1) > Flu (15.6 mumol.L-1) > Cin (25.2 mumol.L-1). All the Dip, Flu, and Cin inhibited 2-components of 5-HT-induced contraction. The antagonistic effects of Dip and Cin on the initial fast-phase contraction (FPC) were greater than that on the sustained tonic-phase contraction (STC), but Flu showed no difference between inhibiting effects on 2-component contractions. CONCLUSION: Dip was more potent than both of Flu and Cin on cerebrovascular dilation, associated mainly with the inhibition of intracellular calcium release.     

Levamisole treatment of a child with severe aphthous stomatitis and neutropenia

The treatment of a 12-year-old girl with a lifelone history of recurrent infections and aphthous stomatitis is reported. A profound neutropenis, first noted at the age of 2 years, occurring at least every month was observed together with multiple mouth ulcers a sore throat and swelling of the jugular glands. Levamisole, originally described as an anthelmintic, has a beneficial effect on the symptoms of recurrent aphthous stomatitis. After levamisole treatment aphthous stomatitis was milder and in the 1-year follow-up period the patient was asymptomatic several times during a phase of obvious neutrophil depression. The child no longer complained of a sore throat with swelling of the jugular glands and the recurrent staphylococcal infections of the skin disappeared. After therapy a marked increase in monocytes at the moment of neutropenia was observed.     

Frequency of the HLA-DP genes and the antigens of the HLA-A, -B, -Cw, and -DR loci in Tuvinians

The results of DNA typing of the HLA-DPB1 gene among Tuvinians are described. The allele 0201 was found to be the most frequent (26.66%); then, in order of decreasing frequency, followed the alleles 0401 (26.42%), 0402 (13.99%), 0301 (8.55%), 0501 (7.77%), 0901 (5.16%), and 1301 (2.07%). The frequency of the allele 0501 in Tuvinians was significantly lower than that in the published data on allele distributions characteristic of two other Mongoloid populations, the Manchu and Japanese. The results of the serological typing of the loci HLA-A, -B, and -Cw of class I in the Tuva population were compared to the corresponding published data on ten Mongoloid populations of Central and Eastern Asia: Uigurs, Kazakhs, Mongols, Manchu, Tibetans, the Chinese of the northern and southern regions of China, Thais (inhabitants of Northwestern Indochina), Koreans, and Japanese. In Tuvinians, the most frequent antigens were HLA-A2, -A9, -B0, -B35, -B17, -Cw4, and -DR5. In the inhabitants of Tuva, the frequency of the antigens HLA-A1, -A9, -B17, -Cw2, and -Cw4 was significantly higher than in other Mongoloids, while that of the antigens HLA-A26 and -B22 was lower. This difference was greatest in the case of antigen HLA-B40: it a frequency of 43.4% was detected in it, while in individuals of Mongolian origin, the frequency of this antigen did not exceed 22.5%. Indices of genetic similarity (IGSs), calculated from the gene frequencies of the loci HLA-A, -B, and -Cw, suggested that the Tuvinians were most closely related to Kazakhs (IGS = 0.73), and least related to the Japanese and Uigurs (IGS = 0.66). Our data suggest that Tuvinians significantly differ from the compared populations of Central and Eastern Asia.     

Identification of HLA-A3 and -B7-restricted CTL response to hepatitis C virus in patients with acute and chronic hepatitis C

We investigated the role of the two highly conserved cysteine residues, cysteines 67 and 95, of the human immunodeficiency virus type 1 (HIV-1) protease in regulating the activity of that protease during viral maturation. To this end, we generated four HIV-1 molecular clones: the wild type, containing both cysteine residues; a protease mutant in which the cysteine at position 67 was replaced by an alanine (C67A); a C95A protease mutant; and a double mutant (C67A C95A). When immature virions were produced in the presence of an HIV-1 protease inhibitor, KNI-272, and the inhibitor was later removed, limited polyprotein processing was observed for wild-type virion preparations over a 20-h period. Treatment of immature wild-type virions with the reducing agent dithiothreitol considerably improved the rate and extent of Gag processing, suggesting that the protease is, in part, reversibly inactivated by oxidation of the cysteine residues. In support of this, C67A C95A virions processed Gag up to fivefold faster than wild-type virions in the absence of a reducing agent. Furthermore, oxidizing agents, such as H2O2 and diamide, inhibited Gag processing of wild-type virions, and this effect was dependent on the presence of cysteine 95. Electron microscopy revealed that a greater percentage of double-mutant virions than wild-type virions developed a mature-like morphology on removal of the inhibitor. These studies provide evidence that under normal culture conditions the cysteines of the HIV-1 protease are susceptible to oxidation during viral maturation, thus preventing immature virions from undergoing complete processing following their release. This is consistent with the cysteines being involved in the regulation of viral maturation in cells under oxidative stress.     

Immunoglobulin deficiencies and impaired immune response to polysaccharide antigens in adult patients with recurrent community-acquired pneumonia

OBJECTIVE: This article reports the results of segmental reversal of the small bowel on parenteral nutrition dependency in patients with very short bowel syndrome. SUMMARY BACKGROUND DATA: Segmental reversal of the small bowel could be seen as an acceptable alternative to intestinal transplantation in patients with very short bowel syndrome deemed to be dependent on home parenteral nutrition. METHODS: Eight patients with short bowel syndrome underwent, at the time of intestinal continuity restoration, a segmental reversal of the distal (n = 7) or proximal (n = 1) small bowel. The median length of the remnant small bowel was 40 cm (range, 25 to 70 cm), including a median length of reversed segment of 12 cm (range, 8 to 15 cm). Five patients presented with jejunotransverse anastomosis, and one each with jejunorectal, jejuno left colonic, or jejunocaecal anastomosis with left colostomy. RESULTS: There were no postoperative deaths. Three patients were reoperated early for wound dehiscence, acute cholecystitis, and sepsis of unknown origin. Three patients experienced transient intestinal obstruction, which was treated conservatively. Median follow-up was 35 months (range, 2 to 108 months). One patient died of pulmonary embolism 7 months postoperatively. By the end of follow-up, three patients were on 100% oral nutrition, one had fluid and electrolyte infusions only, and, in the four other patients, parenteral nutrition regimen was reduced to four (range of 3 to 5) cyclic nocturnal infusions per week. Parenteral nutrition cessation was obtained in 3 of 5 patients at 1 years and in 3 of 3 patients at 4 years. CONCLUSION: Segmental reversal of the small bowel could be proposed as an alternative to intestinal transplantation in patients with short bowel syndrome before the possible occurrence of parenteral nutrition-related complications, because weaning for parenteral nutrition (four patients) or reduction of the frequency of infusions (four patients) was observed in the current study.     

Preliminary evidence for an association of Epstein-Barr virus with pre-ulcerative oral lesions in patients with recurrent aphthous ulcers or Beh?et's disease

In this study we used the polymerase chain reaction (PCR), slot blot and Southern blot hybridization, direct sequencing and in situ hybridization (ISH) to show the possible presence of EBV-DNA in pre-ulcerative oral aphthous lesions of patients with recurrent aphthous ulcers (RAU) or Beh?et's disease (BD). For this purpose, formalin-fixed biopsy specimens were obtained from 13 pre-ulcerative oral aphthous lesions of nine RAU and four BD patients. Five specimens of normal oral mucosa (NOM) from five normal control subjects and 10 specimens of oral erosive or ulcerative lesions from 10 patients with erosive lichen planus (ELP) were also included. EBV-DNA was detected by PCR in 5 of the 13 (38.5%) pre-ulcerative oral aphthous lesions, two from RAU patients and three from BD patients. However, no EBV-DNA was demonstrated in five NOM specimens from normal control subjects and in 10 specimens of oral lesions from ELP patients. EBV-DNA was also demonstrated in patients' peripheral blood lymphocytes and/or plasma, suggesting that the lymphocytes may be the reservoir of latent EBV infection and there is EBV shedding in the plasma. EBV-DNA was detected by ISH in only one PCR-positive case; the reaction product was found to deposit on the nuclei of some of the epithelial cells and lymphocytes. By immunohistochemistry, expression of Epstein-Barr nuclear antigen and EBV/C3d receptors was also noted in some of the epithelial cells and lymphocytes in this ISH-positive case. Therefore, we suggest that the epithelial cells of pre-ulcerative oral aphthous lesions may be infected by EBV through EBV-infected lymphocytes; also, the cytotoxic T lymphocyte-induced lysis of the EBV-infected epithelial cells, but not the virus-induced cytolysis, may be the main mechanism causing oral ulcer formation. Our data provide preliminary evidence for an association of EBV with pre-ulcerative oral aphthous lesions in RAU and BD patients.     

Quantitative assessment of mast cells in recurrent aphthous ulcers (RAU)

Previous studies on the frequency of mast cells (MCs) in recurrent aphthous ulcers (RAU) have yielded conflicting results. Monoclonal antibodies specific for tryptase (AA1) and anti-IgE (polyclonal antibody) were used to identify density and distribution of MCs in an immunohistochemical study of RAU (n=15), induced oral traumatic ulcers (TUs) (n=9), and control clinically healthy oral mucosa (n=15). Results were quantified by means of a VIDAS image analyzer. In all sections studied, IgE-positive cells showed similar frequency and distribution to tryptase-positive MCs. In RAU lesions, numerous tryptase-positive MCs were found in the sub-epithelial lamina propria, but MC numbers in the epithelium were low and present only in some RAU biopsies. MCs were also more numerous in RAU-inflammatory infiltrates (118+/-31 cells/mm2) than those seen in TU-inflammatory infiltrates (75+/-18 cells/mm2, P<0.001). MC activation/degranulation, as judged by diffuse extracellular tryptase staining, was a common feature within RAU-inflammatory infiltrates and at RAU-inflammatory infiltrates-connective tissue interfaces, which were often associated with connective tissue disruption. MC counts in the RAU connective tissue, lateral to the inflammatory infiltrates, were significantly greater than in the connective tissue of TUs and of control biopsies (124+/-36 vs 73+/-13 vs 69+/-21 cells/mm2, respectively; P<0.001). Overall, MCs were significantly increased in aphthae (116+/-26 cells/mm2) compared with TU lesions (72+/-11 cells/mm2, P<0.001) and controls (71+/-16 cells/mm2, P<0.001). In conclusion, MC numbers are increased in a typical topographical pattern, and the local MCs show signs of activation/degranulation suggesting active involvement of this cell type in RAU pathogenesis.     

Expression of laminin 5, fibronectin, and epithelium-associated integrins in recurrent aphthous ulcers

Recurrent aphthous ulceration (RAU) is characterized by an ulcerated lesion that persists longer than traumatic ulcers of similar size. This delayed healing phase of the lesion was investigated for extracellular matrix components and matrix receptors (integrins). The hypothesis tested was that aphthous ulcers may lack key extracellular matrix components, or their receptors, that are necessary for the migration of marginal keratinocytes from the ulcer edge. We immunocytochemically stained biopsy specimens of RAUs and non-involved mucosal specimens from HIV+ and non-infected individuals to investigate the presence and distribution of molecules reported to be associated with reepithelialization of mucosal and cutaneous wounds. Fibronectin, laminin type 5 (kalinin), and integrin subunits beta 1, beta 4, alpha 6, and alpha v were consistently found at the margins of RAU, as they are in traumatic ulcers. The alpha 5 and beta 6 subunits were not always present. We also found alpha v in the intact stratified squamous epithelium adjacent to ulcers. Immunohistochemical stains showed distruption in the deposition of laminin 5 and an apparent lack of fibronectin at the edges of some ulcers. Although these tissue results do not determine which integrin subunits are paired with each other, they do show some alterations in their expression in RAU. Absence of one or more of these molecules at the migrating front may contribute to delayed epithelial regeneration. It is likely that the absence or inappropriate expression of keratinocyte integrins or their extracellular matrix receptors occurs after the causative factors (currently unknown) of the lesion are gone. The reason for the altered expression of these molecules may be related to the secretory products (including lymphokines and proteinases) of the lymphocytic infiltrate.     

The HLA A1-B8 haplotype extends 6 Mb beyond HLA-A: associations between HLA-A, B, F and 15 microsatellite markers

Ornithodoros (Alectorobius) amblus Chamberlin 1920 specimens were collected from a seagull (Larus spp.) nest in northern Chile. This reports the occurrence of this species outside Peru. The biology of 79 specimens reared under laboratory conditions at 27 degrees C, 75-80% RH, and total darkness was determined. A 13% mortality rate from larval to adult was observed. Larval ticks were fed on chicks, Gallus gallus domesticus; and nymphs and adults were fed on chickens. We recorded the number of eggs per female per gonotrophic cycle and the mean duration of the periods of preoviposition, oviposition, and incubation. The total duration of their life cycle ranged from 111 to 239 d, depending on the number of molts. Males were found after the 4th molt, and after the 5th molt the proportion of females was greater than that of males or remaining nymphs. The feeding period of larvae was 4-6 d, N1 nymphs do not feed. The N2-N6 nymphs, males and females, had a 10- to 60-min feeding period. From N2 on, there was emission of coxal fluid while on the host and during or immediately after feeding.     

Detection efficacy of soluble HLA-A, B antigens using 1D-IEF

Soluble HLA class I alloantigens (sHLA class I) can be typed according to their isoelectric points (IEP) after immunoprecipitation by w6/32 monoclonal antibody (mAb) coupled to immunomagnetic beads and focusing. In order to prove the large scale efficacy of this methodology, EDTA-plasma samples from 344 probands HLA-A, B typed by serology were analysed by one-dimensional isoelectric focusing and HLA class I specific Westernblot (1D-IEF). In addition, detergent solubilized HLA class I membrane molecules from approximately one half of the probands were studied too. Soluble HLA-A24,B7,B18,B62 antigens were identified in nearly all experiments, whereas A28, B13, and B51 could be detected in about 50%. A third group of HLA antigens (A26, B8, B44) could be visualized rarely. The difficulties of detection might be due to the different affinity of mAb w6/32 to certain sHLA class I gene products or to variable amounts of sHLA class I in the plasma specimens. Some modifications of the antigen capture technique have already led to a slightly better degree of antigen recognition in 25 probands tested. Thus, HLA-A, B typing using sHLA molecules and 1D-IEF in the assay format presented does not yet seem to be a definitive alternative for HLA class I serology or biochemistry of membrane-bound HLA class I molecules but it should be a promising technique if no cells are available or donor-derived sHLA allotypes are to be monitored after HLA mismatched organ transplantation.     

Factor XIIIa-positive dendrocytes are increased in number and size in recurrent aphthous ulcers (RAU)

The factor XIIIa-positive (FXIIIa+) cell is a potent antigen-presenting cell, which has been described as increasing in numbers in various chronic inflammatory conditions. The purpose of this study was to investigate the distribution and frequency of FXIIIa+ cells in acute recurrent aphthous ulcer (RAU) lesions compared with induced traumatic ulcer (TU) lesions and with clinically healthy oral mucosa. Samples were labeled with polyclonal rabbit anti-human FXIIIa antibodies in avidin-biotin-peroxidase complex (ABC) staining. Most of the FXIIIa-immunoreactive cells in TUs and normal mucosa were spindle-shaped, whereas a relatively large, dendritic-like cell was predominant in RAU lesions. FXIIIa+ cells were quite frequent within mononuclear cell-rich inflammatory cell infiltrates and in perivascular areas in RAU lesions. In contrast, FXIIIa+ cells were not found in mucosal epithelium or in the neutrophil-rich areas. RAU mononuclear cell-rich inflammatory cell infiltrates appeared to have greater numbers of positively stained cells than the TU-inflammatory cell infiltrates (199 +/- 67 vs 110 +/- 31 cells/mm2, P < 0.001). Overall, FXIIIa+ dendrocytes were increased in numbers, and apparently also in size, in RAU lesions (274 +/- 68/mm2) as compared to controls (177 +/- 74/mm2, P < 0.01), and to TU lesions (183 +/- 50 mm2, P < 0.01). Interestingly, relatively high numbers of FXIIIa+ dendrocytes were also found in deep connective tissue in RAU sections compared with TUs (281 +/- 80 vs 166 +/- 57, P < 0.01). The characteristic changes in the size and shape of individual FXIIIa+ cells, their typical distribution and increase in frequency in RAU lesions indicate active involvement in the local pathogenic mechanisms. Localization to perivascular areas/inflammatory cell infiltrates would be compatible with a role in antigen presentation.     

The effect of sodium lauryl sulfate on recurrent aphthous ulcers: a clinical study

This study measured the incidence of recurrent aphthous ulcers during the use of dentifrices with and without sodium lauryl sulfate (SLS). A single-blind, crossover design was used. A statistically significant reduction in recurrent aphthous ulcers was observed during 2 months' use of SLS-free dentifrice compared to 2 months' use of the SLS-containing dentifrice. These results support the results of an earlier independent study, and suggest that use of an SLS-free dentifrice should be considered for individuals suffering from recurrent aphthous ulcers.     

Bronchial reactivity in patients with primary and recurrent pneumonias

Results are submitted of analysis of the external respiration function in rest, under cold test and berotec test in 308 patients with primary pneumonia and 233 patients with recurrent pneumonia. A prominent feature of recurrent pneumonia (unlike the primary one) is the presence of obstruction of the lungs and middle bronchi presenting with hyperreactivity to the cold test and poor response to the broncholytic berotec.     

Brain scanning in patients with recurrent breast cancer

Brain scans were performed on 116 patients with recurrent breast cancer. Seventy-eight of 79 (98%) asymptomatic patients with recurrent disease had negative brain scans. Eleven of 37 (30%) patients with central nervous system (CNS) symptoms had scans indicative of intracranial metastases. There was no difference in the distribution of extracranial metastaic disease in patients who had positive brain scans when compared with those who did not. Brain scaning is of value in detecting intracranial metastases in patients with CNS symptoms. Brain scanning seems unnecessary, however, in the staging of patients with recurrent breast cancer who have no CNS symptoms.