INFLUENCE OF AGING, BEVERAGES, AND MOUTH WASH SOLUTIONS ON THE MICROSTRUCTURAL AND COLOR STABILITY OF DIFFERENT DENTAL CERAMICS: AN IN VITRO STUDY.

Рurроse - to evaluate the influence of aging, beverages, and mouthwash solutions on the microstructural and color stability of three CAD/CAM ceramic materials. In total, 87 specimens (7×5×1.5 mm) were prepared from 3 CAD/CAM ceramic groups, Lithium Disilicate glass ceramic (IPS e.max CAD), Extra translucent zirconia (VITA YZ), and Resin Nanoceramic (Cerasmart 270). All the materials were A2 or equivalent shades. After hydrothermal aging in distilled water at 5 C to 55 C for (10.000 cycles). The samples were randomly allocated into 3 groups (n=27) and immersion (staining) for one week in 3 different solutions coffee, green tea, and chlorhexidine. The baseline measurements of ceramic discs were recorded for color change and 2 samples of each group sent for SEM (microstructure) images before aging and staining. The second measurement was recorded after 10000 thermocycling and immersion in staining agents for 7 days. Statistical analysis were performed with an independent Kruskal-wallis test . The significant level was set at P≤0.05. ∆E values for lithium Disilicate after immersion in coffee, green tea and chlorhexidine gluconate were 3.167, 1.847 and 2.022, respectively. corresponding ∆E values for VITA XT were 3.438, 4.201 and 2.267. meanwhile Cerasmart shows more sensitivity for staining than LD and VITA of 4.454, 2.926 and 2.933. Within limitation of this study lithium disilicate showed the best color stability with values less than perception threshold. VITA and Cerasmart show higher sensitivity for staining with VITA more affected by green tea (Higher than clinically accepted threshold) and Cerasmart more affected by coffee (higher than clinically accepted threshold).

Macroecological patterns of sexual size dimorphism in turtles of the world.

Sexual size dimorphism (SSD) is a well-documented phenomenon in both plants and animals; however, the ecological and evolutionary mechanisms that drive and maintain SSD patterns across geographic space at regional and global scales are understudied, especially for reptiles. Our goal was to examine geographic variation of turtle SSD and to explore ecological and environmental correlates using phylogenetic comparative methods. We use published body size data on 135 species from nine turtle families to examine how geographic patterns and the evolution of SSD are influenced by habitat specialization, climate (annual mean temperature and annual precipitation) and climate variability, latitude, or a combination of these predictor variables. We found that geographic variation, magnitude and direction of turtle SSD are best explained by habitat association, annual temperature variance and annual precipitation. Use of semi-aquatic and terrestrial habitats was associated with male-biased SSD, whereas use of aquatic habitat was associated with female-biased SSD. Our results also suggest that greater temperature variability is associated with female-biased SSD. In contrast, wetter climates are associated with male-biased SSD compared with arid climates that are associated with female-biased SSD. We also show support for a global latitudinal trend in SSD, with females being larger than males towards the poles, especially in the families Emydidae and Geoemydidae. Estimates of phylogenetic signal for both SSD and habitat type indicate that closely related species occupy similar habitats and exhibit similar direction and magnitude of SSD. These global patterns of SSD may arise from sex-specific reproductive behaviour, fecundity and sex-specific responses to environmental factors that differ among habitats and vary systematically across latitude. Thus, this study adds to our current understanding that while SSD can vary dramatically across and within turtle species under phylogenetic constraints, it may be driven, maintained and exaggerated by habitat type, climate and geographic location.

Novel mutation in DOCK8-HIES with severe phenotype and successful transplantation.

BACKGROUND: Hyper-IgE syndrome (HIES) due to DOCK8 deficiency is an autosomal recessive (AR) primary combined immunodeficiency which results in significant morbidity and mortality at a young age. Different mutations in the DOCK8 gene can lead to variable severity of the disease. OBJECTIVE: We evaluated the genetic mutations in three related patients with severe clinical manifestations suggestive of AR HIES. We also explored whether treatment with stem cell transplantation could lead to complete disease resolution. METHOD: We examined the clinical manifestations and immunological workup of these patients. Their DNA was also screened for causative mutation. Post transplantation, clinical and immunological data for the transplanted patient was also collected. RESULTS: All patients had a severe course of the disease with rarely reported severe complications in HIES. One patient died with lymphoma while another died with progressive multifocal leukoencephalopathy (PML) due to a slow virus. All our patients had two novel mutations in the DOCK8 gene. One of these mutations was a novel pathogenic mutation and explains the severity of the disease (homozygous splice site mutation at position 5 after the end of exon 45), while the other mutation was mostly non-pathogenic. Hematopoietic stem cell transplantation (HSCT) was performed in the youngest patient with excellent engraftment and full reversibility of the clinical manifestations. CONCLUSION: We report 3 patients from a consanguineous family diagnosed with AR-HIES due to a novel pathogenic mutation in DOCK8 gene leading to fatal outcome in 2 patients and complete resolution of the clinical and immunological features in the third patient by HSCT.

Loss of NHEJ1 Protein Due to a Novel Splice Site Mutation in a Family Presenting with Combined Immunodeficiency, Microcephaly, and Growth Retardation and Literature Review.

INTRODUCTION: Non-homologous end joining gene 1 (NHEJ1) defect is a rare form of primary immune deficiency. Very few cases have been described from around the world. PURPOSE: We are reporting the first family from the Arabian Gulf with three siblings presenting with combined immunodeficiency (CID), microcephaly, and growth retardation due to a novel NHEJ1 splice site mutation, in addition to a review of the previously published literature on this subject. METHODS: Patients' clinical, immunological, and laboratory features were examined. Samples were subjected to targeted next-generation sequencing (NGS). The pathogenic change in NHEJ1 was confirmed by Sanger sequencing, then further assessed at the RNA and protein levels. RESULTS: Patients were found to have a homozygous splice site mutation immediately downstream of exon 3 in NHEJ1 (c.390 + 1G > C). This led to two distinct mRNA products, one of which demonstrated skipping of the last 69 basepairs (bp) of exon 3 while the other showed complete skipping of the entire exon. Although both deletions were in-frame, immunoblotting did not reveal any NHEJ1 protein products in patient cells, indicating a null phenotype. CONCLUSION: Patients presenting with CID, microcephaly, and growth retardation should be screened for NHEJ1 gene mutations. We discuss our data in the context of one of our patients who is still alive at the age of 30 years, without transplantation, and who is the longest known survivor of this disease.

Arterial pulsatility as an index of cerebral microangiopathy in diabetes type 2.

Transcranial doppler is an inexpensive, non-invasive investigation. This study assessed its validity in determining cerebral small vessel disease in patients with type 2 diabetes mellitus. Flow velocity and pulsatility index were measured in the middle cerebral, basilar and intracranial internal carotid arteries of a sample of 141 diabetic patients with no other risk factors, and 132 age- and sex-matched healthy controls. The patients were divided into 2 groups: 73 with complicated and 68 with uncomplicated diabetes. There was a statistically significant difference between the complicated diabetes and control groups for the 3 arteries and most indices. The differences between the uncomplicated diabetes patients and the controls were also statistically significant but less strongly. Transcranial doppler may be useful in early diagnosis of cerebral small vessel disease in patients with type 2 diabetes mellitus.

Assessment of pain in patients with primary immune deficiency.

BACKGROUND: Primary immune deficiency (PID) patients may develop acute or chronic pain. Pain has not been studied in this population until now. OBJECTIVES: This study systematically assessed the pain of various durations in PID patients using validated pain questionnaires. SUBJECTS AND METHODS: A Short-Form McGill Pain Questionnaire (SF-MPQ), already validated in the Arabic language, was used to ascertain the characteristics and severity of pain. Additionally, an Arabic version of the Neuropathic Pain Questionnaire-Short Form (NPQ-SF) was employed to evaluate neuropathic pain in the same group of patients. RESULTS: Forty-six patients participated in the study. The mean age of the patients was 25 years. The most commonly diagnosed PID was a common variable immune deficiency (32.6%), followed by severe combined immune deficiency (19.57%). Based on the SF-MPQ, the pain was experienced by 30.4 % of the subjects who participated in the study; 57% of whom were on regular pain medications. The most common site reported for pain was the abdomen (35.7%). The mean duration of pain was 36.1 days ± 34.6 days. The most common comorbidities in these patients were bronchiectasis, followed by immune thrombocytopenic purpura, and scoliosis. None of the PID patients had significant neuropathic pain based on NFQ-SF. CONCLUSION: To the best of our knowledge, this is the first study to assess the prevalence as well as the severity and duration of pain in PID patients. There were significantly more subjects who had continuous pain. Treatment of pain in PID patients will have a significant effect on improving their quality of life.

Novel and recurrent mutations in the C1NH gene of Arab patients affected with hereditary angioedema.

BACKGROUND: Autosomal dominant hereditary angioedema (HAE) results in episodes of subcutaneous edema in any body part and/or submucosal edema of the upper respiratory or gastrointestinal tracts. This disorder is caused by mutations in the C1NH gene, many of which have been described primarily in European patients. However, the genetic cause of HAE in Middle Eastern Arab patients has not yet been determined. METHODS: Four unrelated Arab families, in which 15 patients were diagnosed with HAE, were studied. DNA from 13 patients was analyzed for mutations in the C1NH gene by DNA sequencing. RESULTS: Three novel and 2 recurrent mutations were identified in the C1NH gene of HAE patients. In family 1, the patient was heterozygous for a novel c.856C>T and a recurrent c.1361T>A missense mutation encoding for p.Arg264Cys and p.Val432Glu, respectively. In patients from family 2, a novel c.509C>T missense mutation encoding for a p.Ser148Phe was identified. In patients from family 3, a novel c.1142delC nonsense mutation encoding for a p.Ala359AlafsX15 was discovered. In family 4, a recurrent c.1397G>A missense mutation encoding for a p.Arg444His was present. CONCLUSION: This is the first ever report of C1NH gene mutations in Middle Eastern Arab patients. Our study suggests that, despite the numerous existing mutations in the C1NH gene, there are novel and recurrent mutations in HAE patients of non-European origin. We conclude that the spectrum of C1NH gene mutations in HAE patients is wider due to the likely presence of novel and recurrent mutations in patients of other ethnicities.

Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones.

The adoptive transfer of antigen-specific T cells to establish immunity is an effective therapy for viral infections and tumors in animal models. The application of this approach to human disease would require the isolation and in vitro expansion of human antigen-specific T cells and evidence that such T cells persist and function in vivo after transfer. Cytomegalovirus-specific CD8+ cytotoxic T cell (CTL) clones could be isolated from bone marrow donors, propagated in vitro, and adoptively transferred to immunodeficient bone marrow transplant recipients. No toxicity developed and the clones provided persistent reconstitution of CD8+ cytomegalovirus-specific CTL responses.

The t-unique coding domain is important to the transformation maintenance function of the simian virus 40 small t antigen.

The small t antigen (t) of simian virus 40, a 174-amino-acid-containing protein, when present together with the other early viral protein, large T antigen (T), plays an important role in the maintenance of simian virus 40-induced neoplastic phenotype in certain cells. Indeed, each protein functions in a complementary manner in this process. The t coding unit is composed of two segments, a 5' region of 246 nucleotides which is identical to that of the corresponding 5' region of the T coding unit and a 3' segment of 276 nucleotides which is unique. Two mutant, t-encoding genomes, one bearing a missense and the other a nonsense mutation at the same point in the t-unique coding region were constructed in vitro and found to be defective in their ability to dissolve the actin cytoskeleton of rat fibroblasts and to complement T in the growth of mouse fibroblasts in soft agar. Therefore, the unique segment of the t gene encodes a portion of the t molecule which is essential to its transformation maintenance function.

Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans.

The virulence of Candida albicans is dependent upon fitness attributes as well as virulence factors. These attributes include robust stress responses and metabolic flexibility. The assimilation of carbon sources is important for growth and essential for the establishment of infections by C. albicans. Previous studies showed that the C. albicans ICL1 genes, which encode the glyoxylate cycle enzymes isocitratelyase are required for growth on non-fermentable carbon sources such as lactate and oleic acid and were repressed by 2% glucose. In contrast to S. cerevsiae, the enzyme CaIcl1 was not destabilised by glucose, resulting with its metabolite remaining at high levels. Further glucose addition has caused CaIcl1 to lose its signal and mechanisms that trigger destabilization in response to glucose. Another purpose of this study was to test the stability of the Icl1 enzyme in response to the dietary sugars, fructose, and galactose. In the present study, the ICL1 mRNAs expression was quantified using Quantitative Real Time PCR, whereby the stability of protein was measured and quantified using Western blot and phosphoimager, and the replacing and cloning of ICL1 ORF by gene recombination and ubiquitin binding was conducted via co-immuno-precipitation. Following an analogous experimental approach, the analysis was repeated using S. cerevisiaeas a control. Both galactose and fructose were found to trigger the degradation of the ICL1 transcript in C. albicans. The Icl1 enzyme was stable following galactose addition but was degraded in response to fructose. C. albicans Icl1 (CaIcl1) was also subjected to fructose-accelerated degradation when expressed in S. cerevisiae, indicating that, although it lacks a ubiquitination site, CaIcl1 is sensitive to fructose-accelerated protein degradation. The addition of an ubiquitination site to CaIcl1 resulted in this enzyme becoming sensitive to galactose-accelerated degradation and increases its rate of degradation in the presence of fructose. It can be concluded that ubiquitin-independent pathways of fructose-accelerated enzyme degradation exist in C. albicans.

Knowledge and misconceptions about sexually transmitted infections in married women--perspective from Islamabad.

OBJECTIVE: To study the knowledge of married women regarding existence of sexually transmitted infection (STI) their complications, treatment seeking, ways of preventing STI acquisition and opinion about sex education in schools/colleges and media. SETTING: The Mother and Child Health Center, a tertiary care hospital in Islamabad. METHODS: A cross-sectional survey based on sample of convenience was conducted, using a structured questionnaire with both close and open-ended questions. Trained women physician interviewers conducted the interviews after obtaining verbal consent. RESULTS: Out of 218 women approached for interviewing, only two refused to participate in the study. The mean age of the respondents was 28.5 years (range 18-53 years). One hundred and sixty-eight (77.8%) respondents had heard/knew about sexually transmitted infections (STIs). Two hundred and ten (97.2%) respondents had heard/ knew about AIDS and out of these 162 (77.1%) knew that it is also transmitted through sexual contact. One hundred and eighty two (84.2%) felt a need for sex education in the media, both print and electronic and 204 (94.4%) respondents said that they would like to learn more about sexually transmitted infections. One hundred ninety four (98.8%) respondents had heard the Latin term Leukorrhoea. Of these 158 (81.5%) thought it was a gynecological disease. Majority thought it caused weakness. CONCLUSION: Widespread misperceptions were found to exist, which does not augur well for the effective prevention of STIs in the country. Population based studies are required to study the knowledge and epidemiology of STIs, as well as a need for a health education campaign in the country (JPMA 51:389; 2001).

The generation of human dendritic and NK cells from hemopoietic progenitors induced by interleukin-15.

Interleukin-15 (IL-15) is a pleiotropic cytokine that induces the generation and differentiation of lymphoid cells and shares many biological activities with IL-2. We have shown here the development of dendritic cells (DC) from human CD34+ hemopoietic precursor cells cultured for 2-4 weeks with IL-15 alone. DC generated with IL-15 have typical morphological, immunocytochemical, phenotypic, and functional characteristics of mature DC. Dual flow cytometry analysis performed weekly demonstrated increasing co-expression of CD1a or CD83 with HLA-DR, CD80, CD86, IL-2R alpha, beta, and gamma. Two populations of cells were distinguished among CD34+ progeny. Small and medium-size cells were mainly natural killer (NK) cells (72.6-85.2% CD56+) and low numbers of DC (9.1-21.3% CD1a+). Large cells were mostly DC (75.4-95.4% CD1a+). Isolated CD34+ cells did not express IL-2R subunits but after 2-3 days in culture with IL-15, they were found to express IL-2Rgamma. Induced expression of IL-2Rgamma on CD34+ cells may explain the primary mechanism of IL-15-regulated differentiation of hemopoietic precursor cells. Thus, our data suggest that IL-15 stimulates CD34+ cells to differentiate into NK and DC and may represent a new growth and survival factor for lymphoid DC.

First study of pattern of anaphylaxis in a large tertiary care hospital in Saudi Arabia.

BACKGROUND: Anaphylaxis is a serious allergic reaction that may cause death. The signs and symptoms of anaphylaxis have not been examined in the Saudi population before. OBJECTIVE: The present study examined the signs, symptoms, triggers, and demographic patterns of patients treated for anaphylaxis at a large tertiary care hospital in Riyadh, Saudi Arabia. METHODS: All the patients who were prescribed new prescriptions of adrenaline auto-injectors (AAs) between February 1, 2010 and December 31, 2011 were included in this study. Information was collected using a standardized form. RESULTS: There were 238 patients who were analyzed. The median age at the time of first AA prescription was 15.5 years. Female to male ratio was 52:48 and 54% of the subjects were more than 18 years of age. There were some differences in the presenting signs and symptoms observed in our study compared with similar studies from around the world. Urticaria and angioedema were the most common at about 70% across all ages, followed by shortness of breath at 28%. Some triggers were found to be more common in our region. Food was the commonest trigger for anaphylaxis including tree nuts, egg, and sesame. Drug allergy was also a common trigger, with penicillins and nonsteroidal anti-inflammatory drugs being the commonest. Regarding insect allergy, samsam ant was the commonest trigger in our study. CONCLUSION: To our knowledge, this is the first study on anaphylaxis in Saudi Arabia. Some of the manifestations of anaphylaxis are significantly different in our population study compared to previously published data from other parts of the world. While managing anaphylaxis, we should be mindful of these differences. This improved understanding should help reduce the morbidity and mortality associated with anaphylaxis in our region.

Calpain activity in bone marrow transplant-associated thrombotic thrombocytopenic purpura.

The pathophysiology of thrombotic thrombocytopenic purpura (TTP) is not well understood. Recent studies have described a platelet aggregating factor which has been characterized as a calcium-dependent cysteine protease (calpain) in patients with TTP. A type of TTP, sometimes called secondary TTP, has been associated with bone marrow transplantation (BMT). However, unlike primary adult TTP, BMT-TTP has important differences and often does not respond well to plasma exchange. We describe the measurement of calpain activity in a group of BMT patients (with and without the clinical syndrome of transplant-associated TTP). Calpain was measured using a functional assay (14C-serotonin platelet release with inhibition by the cysteine protease inhibitor, leupeptin) in the sera of patients following autologous (auto) or allogeneic (allo) BMT. We also independently diagnosed and graded the BMT-TTP on the day of blood sampling using a scale that related to the percentage schistocytes and lactic dehydrogenase level. Calpain activity was detected in 1/8 (13%) grade 0-1 (6 auto, 2 allo); 6/16 (38%) grade 2 (3 auto, 13 allo) 9/16 (56%) grade 3 (2 auto, 14 allo) and 8/8 (100%) grade 4 BMT-TTP. Pre-BMT samples were tested in 10 allo-BMT patients who had positive calpain results post-BMT. One patient gave positive results before the transplant. This patient developed grade 4 BMT-TTP (day 24 post-BMT) and died despite apheresis. Positive calpain results were highly associated with neurologic symptoms, P < 0.001. Nineteen of 24 (79%) patients with positive results had neurologic symptoms compared to three of 21 (14%) patients with negative results. In conclusion, calpain was detected in half of the BMT patients with mild to moderate BMT-TTP (grades 2-3) and was uniformly found in those with severe (grade 4) BMT-TTP. Typically the calpain activity develops as TTP complicates the transplant process. It is unknown whether calpain contributes to the pathogenesis of this disorder, or is a secondary event.

Hepatitis C virus genotypes and hepatitis G virus in hemodialysis patients from Syria: identification of two novel hepatitis C virus subtypes.

High prevalence of hepatitis C (HCV) and hepatitis G (HGV) viruses has been reported among hemodialysis patients with substantial heterogeneity of HCV genotypes throughout the world. We studied HCV prevalence, clinical significance, genotype distribution, and HGV coinfection in hemodialysis patients from Syria. Ninety (75%) of 120 screened patients were HCV antibody positive. Forty-nine (87.5%) of 56 HCV antibody-positive patients had HCV RNA detected by the polymerase chain reaction. The HCV genotyping was possible in 37 of 49 patients (76%). The HCV genotype distribution was genotype 1a, seven (19%); genotype 1b, 10 (27%); genotype 4a, 11 (30%); unmatched sequences, nine (24%). Phylogenetic analysis of unmatched sequences indicated that they represent two distinct and novel subtypes of HCV genotype 4. Hepatitis G virus RNA was detected in 29 (59%) of the HCV RNA-positive patients. No differences were identified between patients infected with HCV alone and those coinfected with HGV. These data demonstrate that HCV infection is common in this population with a genotype distribution predominantly made up of types 1 and 4. Coinfection with HGV had no effect on the outcome of HCV infection.

Triterpenoid saponins from Bellium bellidioides.

A new acylated triterpenoid saponin carrying the rare 2,3-branched glucose at C-28 of the aglycone bayogenin (2 beta, 3 beta, 23-trihydroxyolean-12-en-28-oic acid) was isolated from the whole plants of Bellium bellidioides. The structure was elucidated mainly by high field NMR experiments (1H and 13C NMR, HMBC, HMQC, COSY-45 at 600/150 MHz) as 3-O-beta-D-glucopyranosyl-28-O-[2-O-alpha-L-rhamnopyranosyl-3-O-beta-D- glucopyranosyl-6-O-acetyl-beta-D-glucopyranosyl]-23-O-acetylbayogenin . Additionally, three acylated derivatives of the known bellissaponin BS1 were obtained.

Specular microscopy, confocal microscopy, and ultrasound biomicroscopy: diagnostic tools of the past quarter century.

PURPOSE: To identify, characterize, and illustrate the most important past and future potential contributions of specular, confocal, and ultrasound biomicroscopy to clinical diagnosis and research applications in the cornea from the past 25 years. METHODS: Specular microscopy, in vivo tandem scanning confocal microscopy (TSCM), scanning slit confocal microscopy (SSCM), and high-frequency ultrasound biomicroscopy are examined. RESULTS AND CONCLUSIONS: This review demonstrates the abilities and limitations of three powerful new in vivo imaging modalities to resolve the cellular and structural layers of the cornea temporally and spatially in three or four dimensions, (x, y, z, t). Clinical pathological processes such as inflammation. infection, wound healing, toxicity, embryonic development, differentiation, and disease, which previously could be studied only under static ex vivo conditions, can now be dynamically evaluated over time. Thus, with continued development and application in vivo, noninvasive microscopic techniques should provide exciting new insights into understanding the structure and function of not only the eye, but also other multicellular organ systems in health and disease. These new imaging paradigms are in the first rank of advances in medical science in the past quarter century.

Tear IgA and serum IgG antibodies against Acanthamoeba in patients with Acanthamoeba keratitis.

PURPOSE: Exposure to Acanthamoebaspecies appears to be ubiquitous, as 50% to 100% of healthy human subjects display anti-Acanthamoebaantibodies. However, the presence of specific anti-Acanthamoebaantibodies in the serum and tears of patients has not been investigated. The prevalence of serum immunoglobulin G (IgG) and tear IgA against three species of Acanthamoebawas assessed in healthy subjects and patients with Acanthamoebakeratitis. METHODS: The level of specific serum IgG and tear IgA against A. castellanii, A. astronyxis, and A. culbertsoniin the sera of 23 patients and 25 healthy subjects was tested by enzyme-linked immunosorbent assays. Total serum IgM, IgG, and IgA concentrations were measured by nephelometry. Acanthamoebakeratitis was diagnosed clinically and confirmed by in vivo confocal microscopy. In some patients, corneal biopsies were also performed and trophozoites were cultured on lawns of Escherichia colion non-nutrient agar. RESULTS: All healthy subjects and patients with Acanthamoebakeratitis had detectable serum IgG antibodies against all Acanthamoebaantigens. However, patients with Acanthamoebakeratitis had significantly higher anti-AcanthamoebaIgG antibody titers than healthy subjects. In contrast, Acanthamoeba-specific tear IgA was significantly lower in patients with Acanthamoebakeratitis in comparison with healthy subjects. Total serum immunoglobulins did not differ significantly between healthy subjects and patients with Acanthamoebakeratitis. CONCLUSIONS: The results suggest that a low level of anti-AcanthamoebaIgA antibody in the tears appears to be associated with Acanthamoebakeratitis.

Immunohistochemical study of proliferating mesenchymal spindle cells in heterogenous soft tissue lesions.

Proliferation of mesenchymal spindle cells is a main event in a variety of lesions with similar morphological features but widely divergent biological behaviour. In order to identify criteria for precise histological diagnosis, 60 human soft tissue lesions, divided into 40 cases of fibroblastic cell proliferation, 10 smooth muscle cell tumours and 10 nerve sheath cell tumours, were examined for the immunohistochemical profile of the main lesional cell in addition to other histological features. The three groups could be differentiated by determining the lineage of the constituent spindle cell on the pattern of expression of vimentin, alpha-smooth muscle actin (ASMA) and macrophage antigen CD68 (MA-CD68). Smooth muscle cells expressed ASMA and vimentin but not MA-CD68, while nerve sheath cells were negative for ASMA but positive for vimentin and MA-CD68. The fibroblastic cell lesions as a group were easily differentiated on the basis of positive reactivity for all three markers but individual lesions could only be distinguished by additional assessment of histological features. Because of consistent co-expression of ASMA, vimentin and MA-CD68 in the spindle mesenchymal cell present in all varieties of lesions in this heterogeneous group, we suggest that this proliferating "fibroblastic" cell is phenotypically a fibromyohistiocyte.