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Angioleiomyomas are uncommon, noncancerous, smooth muscle tumors that primarily arise from blood vessels. Previous studies have yielded limited data due to the lack of interdisciplinary approaches or restricted patient pools. This study aims to provide a comprehensive analysis of angioleiomyomas, including the demographic, clinical, radiological, and histopathological features, with a large number of patients. Conducted as a retrospective investigation at a single center from January 2005 to June 2023, this study involved 142 patients. Relevant information was extracted from electronic medical records, covering clinical, radiological, histological, and demographic details. Angioleiomyomas mostly occurred at age 59 (1–87), predominately affect females (53%) and commonly arise in subcutaneous tissue (85%) and the lower limbs (76%). MRI findings revealed characteristic signals, with a high prevalence of the solid histologic type (65%), often displaying a reticular sign. Smooth muscle Actin was universally present (n = 95/95), while Desmin and Caldesmon showed positive expression in 83% (n = 71/85) and 98% (n = 92/94) of cases, respectively. This study presents an updated and comprehensive analysis of angioleiomyomas. Typically appearing as well-defined nodules in the extremities, these tumors can be effectively diagnosed using MRI, though histopathological analysis is generally essential for confirmation. Treatment primarily involves straightforward excision, with notable low complication and recurrence rates. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung dysfunction due to excessive collagen production and tissue scarring. Despite recent advancements, the molecular mechanisms remain unclear. Methods: RNA sequencing identified 475 differentially expressed genes (DEGs) in the TGF-b1-induced primary lung fibrosis model. Gene expression chips GSE101286 and GSE110147 from NCBI gene expression omnibus (GEO) database were analyzed using GEO2R, revealing 94 DEGs in IPF lung tissue samples. The gene ontology (GO) and pathway enrichment, Protein-protein interaction (PPI) network construction, and Maximal Clique Centrality (MCC) scoring were performed. Experimental validation included RT-qPCR, Immunohistochemistry (IHC), and Western Blot, with siRNA used for gene knockdown. A co-expression network was constructed by GeneMANIA. Results: GO enrichment highlighted significant enrichment of DEGs in TGF-b cellular response, connective tissue development, extracellular matrix components, and signaling pathways such as the AGE-RAGE signaling pathway and ECM-receptor interaction. PPI network analysis identified hub genes, including FN1, COL1A1, POSTN, KIF11, and ECT2. CALD1 (Caldesmon 1), CDH2 (Cadherin 2), and POSTN (Periostin) were identified as dysregulated hub genes in both the RNA sequencing and GEO datasets. Validation experiments confirmed the upregulation of CALD1, CDH2, and POSTN in TGF-b1-treated fibroblasts and IPF lung tissue samples. IHC experiments probed tissue-level expression patterns of these three molecules. Knockdown of CALD1, CDH2, and POSTN attenuated the expression of fibrotic markers (collagen I and a-SMA) in response to TGF-b1 stimulation in primary fibroblasts. Co-expression analysis revealed interactions between hub genes and predicted genes involved in actin cytoskeleton regulation and cell-cell junction organization. Conclusions: CALD1, CDH2, and POSTN, identified as potential contributors to pulmonary fibrosis, present promising therapeutic targets for IPF patients. [ABSTRACT FROM AUTHOR]

Cancer is a profound medical concern and better treatments are needed for cancer patients. Therefore, new cancer targets are constantly being studied. These targets need not only be relevant for cancer progression, but their modulation needs to be tolerated reasonably well by the host. Caldesmon is one of these proposed novel targets for cancer therapy. Therefore, we analyzed effects of caldesmon mutations in normal development using genetically modified zebrafish embryos. We analyzed mutations in both zebrafish caldesmon genes, cald1a and cald1b and analyzed effects of either mutation alone or as in combination in double homozygous embryos using molecular, morphological and functional analyses. The effects of caldesmon mutations were mild and the gross development of zebrafish embryos was normal. The caldesmon mutant embryos had, however, alterations in response to light-stimulus in behavioural assays. Taken together, the effects of caldesmon mutations in the development of zebrafish embryos were reasonably well tolerated and did not indicate significant concerns for caldesmon being a potential target for cancer therapy. • Mutations in caldesmon genes were not embryonic lethal in zebrafish model. • Mutation of either cald1a , cald1b or both together did not result in gross morphological defects in zebrafish embryos. • Cald1 mutation had mild effects on the behavior of zebrafish embryos. [ABSTRACT FROM AUTHOR]

Stretch-induced vascular tone is an important element of autoregulatory adaptation of cerebral vasculature to maintain cerebral flow constant despite changes in perfusion pressure. Little is known as to the regulation of tone in senescent basilar arteries. We tested the hypothesis, that thin filament mechanisms in addition to smooth muscle myosin-II regulatory-light-chain- (MLC20)-phosphorylation and non-muscle-myosin-II, contribute to regulation of stretch-induced tone. In young BAs (y-BAs) mechanical stretch does not lead to spontaneous tone generation. Stretch-induced tone in y-BAs appeared only after inhibition of NO-release by L-NAME and was fully prevented by treatment with 3 µmol/L RhoA-kinase (ROK) inhibitor Y27632. L-NAME-induced tone was reduced in y-BAs from heterozygous mice carrying a point mutation of the targeting-subunit of the myosin phosphatase, MYPT1 at threonine696 (MYPT1-T696A/+). In y-BAs, MYPT1-T696A-mutation also blunted the ability of L-NAME to increase MLC20-phosphorylation. In contrast, senescent BAs (s-BAs; >24 months) developed stable spontaneous stretch-induced tone and pharmacological inhibition of NO-release by L-NAME led to an additive effect. In s-BAs the MYPT1-T696A mutation also blunted MLC20-phosphorylation, but did not prevent development of stretch-induced tone. In s-BAs from both lines, Y27632 completely abolished stretch- and L-NAME-induced tone. In s-BAs phosphorylation of non-muscle-myosin-S1943 and PAK1-T423, shown to be down-stream effectors of ROK was also reduced by Y27632 treatment. Stretch- and L-NAME tone were inhibited by inhibition of non-muscle myosin (NM-myosin) by blebbistatin. We also tested whether the substrate of PAK1 the thin-filament associated protein, caldesmon is involved in the regulation of stretch-induced tone in advanced age. BAs obtained from heterozygotes Cald1+/- mice generated stretch-induced tone already at an age of 20-21 months old BAs (o-BA). The magnitude of stretch-induced tone in Cald1+/- o-BAs was similar to that in s-BA. In addition, truncation of caldesmon myosin binding Exon2 (CaD-ΔEx2-/-) did not accelerate stretch-induced tone. Our study indicates that in senescent cerebral vessels, mechanisms distinct from MLC20 phosphorylation contribute to regulation of tone in the absence of a contractile agonist. While in y-and o-BA the canonical pathways, i.e., inhibition of MLCP by ROK and increase in pMLC20, predominate, tone regulation in senescence involves ROK regulated mechanisms, involving non-muscle-myosin and thin filament linked mechanisms involving caldesmon. [ABSTRACT FROM AUTHOR]

Stretch-induced vascular tone is an important element of autoregulatory adaptation of cerebral vasculature to maintain cerebral flow constant despite changes in perfusion pressure. Little is known as to the regulation of tone in senescent basilar arteries. We tested the hypothesis, that thin filament mechanisms in addition to smooth muscle myosin-II regulatory-light-chain-(MLC20)-phosphorylation and non-muscle-myosin-II, contribute to regulation of stretch-induced tone. In young BAs (y-BAs) mechanical stretch does not lead to spontaneous tone generation. Stretch-induced tone in y-BAs appeared only after inhibition of NO-release by L-NAME and was fully prevented by treatment with 3 μmol/L RhoA-kinase (ROK) inhibitor Y27632. L-NAME-induced tone was reduced in y-BAs from heterozygous mice carrying a point mutation of the targeting-subunit of the myosin phosphatase, MYPT1 at threonine696 (MYPT1-T696A/+). In y-BAs, MYPT1-T696A-mutation also blunted the ability of L-NAME to increase MLC20-phosphorylation. In contrast, senescent BAs (s-BAs; >24 months) developed stable spontaneous stretch-induced tone and pharmacological inhibition of NO-release by L-NAME led to an additive effect. In s-BAs the MYPT1-T696A mutation also blunted MLC20-phosphorylation, but did not prevent development of stretch-induced tone. In s-BAs from both lines, Y27632 completely abolished stretch- and L-NAME-induced tone. In s-BAs phosphorylation of non-muscle-myosin-S1943 and PAK1-T423, shown to be down-stream effectors of ROK was also reduced by Y27632 treatment. Stretch- and L-NAME tone were inhibited by inhibition of non-muscle myosin (NM-myosin) by blebbistatin. We also tested whether the substrate of PAK1 the thin-filament associated protein, caldesmon is involved in the regulation of stretch-induced tone in advanced age. BAs obtained from heterozygotes Cald1+/− mice generated stretch-induced tone already at an age of 20–21 months old BAs (o-BA). The magnitude of stretch-induced tone in Cald1+/− o-BAs was similar to that in s-BA. In addition, truncation of caldesmon myosin binding Exon2 (CaD-▵Ex2−/−) did not accelerate stretch-induced tone. Our study indicates that in senescent cerebral vessels, mechanisms distinct from MLC20 phosphorylation contribute to regulation of tone in the absence of a contractile agonist. While in y-and o-BA the canonical pathways, i.e., inhibition of MLCP by ROK and increase in pMLC20, predominate, tone regulation in senescence involves ROK regulated mechanisms, involving non-muscle-myosin and thin filament linked mechanisms involving caldesmon.

Colorectal cancer is a notorious disease, with almost half of the patients succumbing to the disease. The prevalence and incidence rates of colorectal cancer are increasing in many parts of the world, highlighting the need to discover new biomarkers for diagnosis and therapy. Caldesmon (CaD), an actin-binding protein that plays a significant role in controlling cell motility, has emerged as a promising biomarker. The CALD1 gene encodes CaD as multiple transcripts that mainly encode two protein isoforms: High-molecular-weight (h-CaD), expressed in smooth muscle, and low-molecular-weight (l-CaD), expressed in nonsmooth muscle cells. Most studies have suggested an oncogenic role of CaD in colorectal cancer, but the exact subcellular localization of the two CaD isoforms in tumor cells and stroma have not been clarified yet. Here, we analyzed tissue samples from 262 colorectal cancer patients by immunohistochemistry analysis using specific antibodies for l-CaD and h-CaD. The results showed elevated cytoplasmic expression levels of l-Cad in 187/262 (71.4%) cases. l-Cad was expressed at low levels in the normal colon mucosa and was also consistently expressed in the cancer-associated stroma of all cases, suggesting that it could play a role in modulating the tumor microenvironment. l-CaD expression in cancer cells was associated with preinvasive stages of cancer. Survival analysis indicated that patients with high l-CaD expression in tumor cells could respond poorly to selective chemotherapeutic 5FU, but not combination chemotherapy. h-CaD was expressed in colonic and vascular smooth muscle cells as expected and to a lesser extent in the tumor-associated stroma, but it was not expressed in the cancer cells or normal colon mucosal epithelial cells. Collectively, these data clarify how the expression patterns of CaD isoforms in colorectal cancer can have applications in the management of colorectal cancer patients. [ABSTRACT FROM AUTHOR]

Soft tissue tumors with smooth muscle differentiation are rare in pediatric patients. Despite often showing morphologic features sufficient for classification as "leiomyosarcoma" in adults (e.g., high cellularity, mitotic activity), clinical follow-up has shown only indolent behavior. The pathological features of recently reported SRF-rearranged "cellular myofibromas/myopericytomas", typically occurring in children, overlap with those of true smooth muscle tumors. We studied a large series of pediatric tumors with morphologic and immunohistochemical evidence of smooth muscle differentiation, with the goals of better understanding their natural history and molecular genetic features. Seventy-eight tumors were identified occurring in 45 males and 33 females, with a median age of 10 years. Clinical follow-up (50 patients; median 45.5 months) disclosed local recurrence in 7 patients (15%). No metastases or deaths due to disease occurred. Group 1 (73/78) tumors consisted of cellular fascicles of mildly to at most moderately atypical, bland, ovoid to spindled cells with distinctly eosinophilic cytoplasm, appreciable mitotic activity (median 5/50 HPF) and no necrosis. Group 2 tumors (5/78) showed greater cellularity, significant nuclear pleomorphism, and brisk mitotic activity (median 59/50 HPF). Subsets of group 1 tumors harbored SRF rearrangements (16/47) and all group 2 tumors showed TP53 biallelic inactivation (5/5). SRF fusion partners included CITED1, NCOA2, C3orf62, RELA, ARGFXP1, ARNTI2, ICA1L, and unknown (n=1). We conclude that the prognosis for pediatric tumors with smooth muscle differentiation that fall into group 1 is excellent. SRF rearrangements are present in a significant minority of tumors, typically showing features of smooth muscle, rather than myopericytic differentiation. A smaller subset with more worrisome morphologic features harbor biallelic inactivation of TP53. To emphasize their unique features, we propose the term "pediatric-type myoid neoplasms of somatic soft tissue," rather than simply "leiomyoma" or "leiomyosarcoma" for group 1 tumors and the designation of leiomyosarcoma in children should be limited to group 2 tumors., (Copyright © 2025. Published by Elsevier Inc.)

Primary leiomyosarcoma (PLMS) of the ovary is extremely rare tumors comprising 1% of ovarian tumors. About 3% of all ovarian malignancies are primary ovarian sarcomas. Only 72 cases have been reported till date. A 57-year-old postmenopausal female presented with abdominal pain for the last 6 months. Ultrasonography and MRI revealed a heterogeneously enhancing solid lobulated mass in the left adnexa abutting the fundus of the uterus and bowel loops. The endometrial cavity was normal. Ovarian markers CA 125, CEA, CA 19.9, and all hematological parameters were within normal limits. LDH was near normal (284 IU/ml). The specimen was sent for frozen section and a diagnosis of malignant spindle cell lesion of ovary was rendered. Histopathology of the ovarian mass revealed intersecting fascicles of tumor cells consisting of ovoid to spindle-shaped cells having a moderate amount of cytoplasm. Bizarre and atypical cells were seen singly dispersed and in small aggregates along with the brisk mitotic activity. Focal areas of necrosis and hemorrhage were also noted. Immunohistochemistry showed strong positivity for smooth muscle actin and Caldesmon while focal positivity for Desmin and Epithelial Membrane Antigen (EMA) was noted. The lesion was negative for Inhibin, Calretinin, and CD 117 and S100. The final diagnosis of primary ovarian Leiomyosarcoma was given based on histopathology and Immunohistochemistry. PLMS of the ovary are rare incidental findings in postmenopausal women. These are highly malignant tumors and carry a poor prognosis. Hence, early diagnosis and surgical treatment with cytoreduction improve patient survival.

Nevoid basal cell carcinoma syndrome (NBCCS) associated odontogenic keratocysts (OKCs) show more aggressive behavior and it has a higher frequency of relapse than non-syndromic OKCs. Stromal myofibroblasts (MFs), characterized by α-smooth muscle actin (αSMA), desmin and caldesmon expression, and metalloproteinases (MMPs) have an essential role in the remodeling of the extracellular matrix (ECM). The aim of the study is to analyze the immunohistochemical expression of MMP-7, MMP-9, αSMA and other new markers in the study of OKCs MFs such as desmin and caldesmon in NBCCS-associated OKCs compared to recurrent and sporadic keratocysts. Fourty 40 patients (23 M and 17 F) underwent surgery to remove the OKCs. The histological sections in paraffin were incubated with markers antibodies and a semi-quantitative score was used to evaluate the immunoreactivity. Densitometric analysis showed a very significantly increased expression of αSMA, caldesmon, MMP-7 and MMP-9 in NBCCS-OKCs compared to non-syndromic OKCs (p < 0.001). However, desmin showed a not significant increased expression in non-syndromic OKC compared to NBCCS-OKCs specimens in which desmin was slightly or not at all expressed. NBCSS-OKCs showed a greater distribution of MFs compared to the other OKCs subtypes. Further studies will be needed to evaluate whether the different expressions of these markers can be correlated to a different clinical behavior. [ABSTRACT FROM AUTHOR]

Different challenges are being applied in the poultry industry in order to protect animal health and to increase immunity and production. The supplementation of microbial phytase is essential in terms of both reducing the inorganic phytase rate and contributing to the absorption of other minerals. In this study, a newly isolated microbial phytase was added at different concentrations to the diet together with calcium (Ca2+) and available phosphorus (AP), and the effects of this supplementation on intestinal absorption capacity and Ca2+ binding capacity were investigated via morphological measurements and immunohistochemical examination of the duodenum and ileum. For this purpose, 90 Lohmann LSL-White laying hens were divided into three main diet groups: 1. Standard Ca2+ and AP (Ca+AP), 2. Standard Ca2+ and low AP (Ca+low AP), and 3. Low Ca2+ and low AP (low Ca+low AP). These three groups were further divided into three phytase subgroups each (without phytase [Phy-], commercial phytase [CP] and microbial phytase [MP]). At the end of the experiment, animals were euthanized, and duodenum and ileum samples were fixed and processed for histological examination. Villus height, crypt depth, total mucosa thickness, and villus width were measured and villus height: crypt depth ratio and villus absorption area were calculated. Caldesmon expression in the duodenum and ileum was also investigated immunohistochemically. The results indicated that villus height, total mucosa thickness, and villus absorption area increased (p = 0.05) in birds fed with Ca+AP+MP. Stronger caldesmon expression was observed in the MP treated groups. We concluded that MP produced from Bacillus megaterium EBD 9-1 bacterium increases the utilization of Ca2+ and AP and, thus, can have a beneficial role when these macrominerals are used insufficiently. Ca2+, AP, and MP may have positive effects on the intestinal morphology and absorption area when used at optimum amounts. [ABSTRACT FROM AUTHOR]

Myopericytoma is an uncommon benign neoplasm that arises from the perivascular myoid cells. It typically presents as a painless well-circumscribed cutaneous or soft-tissue nodule, most commonly on the extremities of adults. Histologically, it is characterized by spindle-shaped myoid-appearing cells with a concentric arrangement in vessel walls, that are immunoreactive to alpha-smooth muscle actin and often for h-caldesmon, but negative for other smooth muscle markers. Herein, we present an unusual case of a painful subungual myopericytoma presenting as a dark subungual discoloration. [ABSTRACT FROM AUTHOR]

Canine oral malignant melanomas (OMMs) exhibit a variety of morphologic phenotypes, including a spindloid variant. The microscopic diagnosis of spindloid OMMs is based on junctional activity and/or the presence of melanin pigment. In the absence of these features, spindloid OMMs are difficult to differentiate from soft tissue sarcomas (STS). An antibody cocktail (MDX) that includes Melan-A, PNL2, and tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2) is the current gold standard for identifying amelanotic OMMs by immunohistochemistry (IHC). However, MDX is less sensitive for diagnosing spindloid amelanotic OMMs. This raises concern for biopsy specimens that lack overlying epithelium, making it potentially difficult to differentiate OMM from STS by IHC. The goal of this study was to identify additional markers to help differentiate between STS and OMMs that lack pigment and junctional activity. SOX-10 has recently been proposed as a sensitive marker for melanocytes in humans but has not been validated in dogs. Similarly, RNA expression for various genes has been analyzed in humans, but not in the context of diagnosing canine melanocytic neoplasms. For this retrospective study, formalin-fixed, paraffin-embedded tissues from 20 OMMs, 20 STS, and 20 oral spindle cell tumors (OSCTs) that lacked junctional activity and pigmentation were selected. IHC for MDX, SOX-10, and laminin, in parallel with RT-qPCR of TYR, SOX10, CALD1, CD34, DES, and LAMA1, was performed in all cases. TYR, CD34, and CALD1 were the most discriminatory genes in differentiating between OMM and STS, all having 100% specificity and 65, 95, and 60% sensitivity, respectively. While all 20 OMMs were immunohistochemically labeled for SOX-10, two STS were also labeled (100% sensitivity and 90% specificity). MDX IHC labeled all 20 OMMs and no STS. Surprisingly, none of the 20 OSCTs expressed TYR RNA above the cutoff, and 14/20 OSCTs expressed CALD1 or CD34 RNA above the cutoff, thereby confirming them as STS. Four OSCT were suspect STS, and no OSCTs were confirmed as OMMs based on IHC and RNA expression patterns. In conclusion, the RNA levels of TYR, CD34, and CALD1 should be evaluated in suspected amelanotic OMMs that are negative for MDX to accurately differentiate between OMM and STS.

Caldesmon, an actin-binding protein, can inhibit myosin binding to actin and regulate smooth muscle contraction and relaxation. However, caldesmon has recently attracted attention due to its importance in cancer. The upregulation of caldesmon in several solid cancer tissues has been reported. Caldesmon, as well as its two isoforms, is considered as a biomarker for cancer and a potent suppressor of cancer cell invasion by regulating podosome/invadopodium formation. Therefore, caldesmon may be a promising therapeutic target for diseases such as cancer. Here, we review new studies on the gene transcription, isoform structure, expression, and phosphorylation regulation of caldesmon and discuss its clinical implications in cancer.

Background: Duchenne muscular dystrophy (DMD) is characterized by the lack of dystrophin in skeletal, cardiac, and smooth muscle. Slow colonic transit and constipation are common in DMD patients and animal models of DMD. However, the cause of this hypocontractility and the expression of contractile proteins in smooth muscle are unknown. The aim of the study was to investigate the expression of contractile proteins in the colonic smooth muscle and the function of the colon in control and mdx mice. Methods: Muscle contraction was measured in muscle strips and isolated muscle cells. Peristaltic activity was measured in ex vivo preparations by spatiotemporal mapping, and gastrointestinal (GI) transit in vivo was measured by the distribution of fluorescent marker along the intestine and colon. mRNA expression of contractile proteins smoothelin, caldesmon, calponin, and tropomyosin was measured by qRT‐PCR. Results: Expression of mRNA for contractile proteins was decreased in colonic smooth muscle of mdx mice compared with control. Contraction in response to acetylcholine and KCl was decreased in colonic muscle strips and in isolated muscle cells of mdx mice. Distension of ex vivo colons with Krebs buffer induced peristalsis in both control and mdx mice; however, significantly fewer full peristaltic waves were recorded in the colons of mdx mice. GI transit was also inhibited in mdx mice. Conclusion and Inferences: The data indicate that the lack of dystrophin causes decrease in colonic smooth muscle contractility, peristalsis, and GI transit and provides the basis for analysis of mechanisms involved in smooth muscle dysfunction in DMD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fibrous pseudotumor is a rare benign lesion, reactive in nature, which can appear in the form of nodules (single or multiple) or diffusely in the testicular tunics. Clinically it simulates a malignant tumor, so the treatment consists of radical orchiectomy. CLINICAL CASE: A 70-year-old man, who came to the clinic due to an increase in testicular volume of several months of evolution. Ultrasound revealed a right simple hydrocele, 170 cm3. Treatment consisted of hydrolectomy, using the right hemiscrotal technique. In the surgical act, multiple nodules adhered to the tunica vaginalis and albuginea were evidenced. Immunohistochemistry showed positivity for caldesmon and CK (AE1 / AE3), and negativity for desmin, actin, CD34, CD31, calretinin, EMA, CK7, CK5 / 6 and WT1. The final diagnosis was: multiple nodular fibrous pseudotumor. CONCLSUIONS: It is important to know the fibrous pseudotumor, since when obtaining an intraoperative biopsy it can be confused with a high-grade lesion. The possibility of IgG4 disease should be ruled out, because it is a systemic disease that can affect any location. [ABSTRACT FROM AUTHOR]

Abstract Smooth muscle cell (SMC) regeneration plays an important role in retrieving the bladder-wall functionality and it can be achieved by a proper cell- co -polymer constructed by tissue engineering. Human induced pluripotent stem cells (iPSCs), which can be specifically prepared for the patient, was considered as cells in this study, and Poly(lactide- co -glycolide) (PLGA) as a most interesting polymer in biomedical applications was applied to the scaffold fabrication by electrospinning. After scaffold characterization, SMC differentiation potential of the human iPSCs was investigated while cultured on the PLGA nanofibrous scaffold by evaluation of the SMC related important gene and protein markers. Alpha-smooth muscle actin (ASMA), Smooth muscle 22 alpha (SM-22a) as two early SMC markers were significantly up regulated either two and three weeks after differentiation induction in human iPSCs cultured on PLGA compared to those cells cultured on the tissue culture polystyrene (TCPS). But Calponin-1, Caldesmon1 and myosin heavy chain (MHC) expression differences in human iPSCs cultured on PLGA and TCPS were significant only three weeks after differentiation induction based on its lately expression in the differentiation process. ASMA and MHC proteins were also considered for evaluation by immunocytochemistry on differentiated iPSCs whereas results showed higher expression of these proteins in stem cells grown on PLGA compared to the TCPS. According to the results, human iPSCs demonstrated a great SMC differentiation potential when grown on PLGA and it could be considered as a promising cell- co -polymer for use in bladder tissue engineering. Highlights • PLGA nanofibers was fabricated by electrospinning method. • Nanofibrous scaffold characterized using SEM, contact angle, Tensile and MTT assays. • SMC differentiation potential of the iPSCs was investigated while cultured on PLGA. • SMC related gene and protein markers were used for differentiation evaluation. • Evaluations demonstrated higher SMC differentiation in iPSCs while cultured on PLGA. [ABSTRACT FROM AUTHOR]

Purpose: The decreased placental perfusion is the underlying reason for intrauterine growth restriction that in turn leads to reduced placental perfusion and ischemia. However, there are several issues to be understood in the pathophysiology of intrauterine growth restriction. We aimed to study whether any compensatory response in placental vascular bed occur in pregnancies complicated with intrauterine growth restriction by the immunohistochemical staining of von Willebrand factor and caldesmon in placental tissues.Materials and Methods: A total of 103 pregnant women was enrolled in the study including 50 patients who were complicated with IUGR and 50 uncomplicated control patients. The study was designed in a prospective manner. All placentas were also stained with von Willebrand factor and caldesmon monoclonal kits.Results: The immunohistochemical staining of von Willebrand factor and caldesmon expressions in placental tissues were different between normal and intrauterine growth restriction group. The percentages of 2+ and 3+ von Willebrand factor expression were higher in the intrauterine growth restriction group comparing with the normal group, although the difference was not statistically significant. The intensity of caldesmon expression was significantly lower in the intrauterine growth restriction group in comparison with the normal group (p < .001).Conclusion: Angiogenesis occurs as a placental response to intrauterine growth restriction which is a hypoxic condition. But newly formed vessels are immature and not strong enough. Our study is important to clarify the pathophysiology and placental compensatory responses in intrauterine growth restriction. [ABSTRACT FROM AUTHOR]

Soft tissue sarcomas (STS) are rare mesenchymal neoplasms arising from nonepithelial connective tissue origins. Retroperitoneal Soft tissue sarcomas may be primary tumours or metastases especially from the uterus. Here, the authors present a case of intrapelvic leiomyosarcoma treated with hormonotherapy after surgery. A 40-year-old multiparous woman was admitted to the hospital with abdominal pain. Abdominopelvic ultrasound was performed, and an uncircmuscribed mass was seen in the Douglas pouch. At laparotomy, a tumour measuring 7 cm in size, appearing as a sarcoma attached to the sigmoid colon serosa was found. The tumour was positive with H-caldesmon, actin, desmin, oestrogen and progesterone receptors (ER/PR). The patient with a diagnosis of low-grade intrapelvic leiomyosarcoma received adjuvant hormonotherapy after adjuvant radiotherapy. She is doing well without disease recurrence during a two-year follow-up period. Despite contradictory data according to recent limited investigations, the present authors suggest that ER and PR should be routinely quantified in STS by immunohistochemical methods, and it should be kept in mind that hormonotherapy may be a beneficial option. [ABSTRACT FROM AUTHOR]

Background: Osteoclasts (OCs) are motile multinucleated cells derived from differentiation and fusion of hematopoietic progenitors of the monocyte-macrophage lineage that undergo a multistep process called osteoclastogenesis. The biological function of OCs is to resorb bone matrix for controlling bone strength and integrity, which is essential for bone development. The bone resorption function is based on the remodelling of the actin cytoskeleton into an F-actin-rich structure known as the sealing zone for bone anchoring and matrix degradation. Non-muscle caldesmon (l-CaD) is known to participate in the regulation of actin cytoskeletal remodeling, but its function in osteoclastogenesis remains unclear. Methods/results: In this study, gain and loss of the l-CaD level in RAW264.7 murine macrophages followed by RANKL induction was used as an experimental approach to examine the involvement of l-CaD in the control of cell fusion into multinucleated OCs in osteoclastogenesis. In comparison with controls, l-CaD overexpression significantly increased TRAP activity, actin ring structure and mineral substrate resorption in RANKL-induced cells. In contrast, gene silencing against l-CaD decreased the potential for RANKL-induced osteoclastogenesis and mineral substrate resorption. In addition, OC precursor cells with l-CaD overexpression and gene silencing followed by RANKL induction caused 13% increase and 24% decrease, respectively, in cell fusion index. To further understand the mechanistic action of l-CaD in the modulation of OC fusion, atomic force microscopy was used to resolve the mechanical changes of cell spreading and adhesion force in RANKL-induced cells with and without l-CaD overexpression or gene silencing. Conclusions: l-CaD plays a key role in the regulation of actin cytoskeletal remodeling for the formation of actin ring structure at the cell periphery, which may in turn alter the mechanical property of cell-spreading and cell surface adhesion force, thereby facilitating cell-cell fusion into multinucleated OCs during osteoclastogenesis. [ABSTRACT FROM AUTHOR]

Abstract The goals of this study were to examine the cellular signaling pathways associated with the phosphorylation of caldesmon, the phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17), and the 20-kDa regulatory light chain of myosin (MLC 20) induced by levobupivacaine in isolated rat aortas. The effects of genistein, tyrphostin 23, GF109203X, PD98059, Y-27632, 1-butanol, and ML-7 HCl on levobupivacaine-induced contraction were assessed. The effect of genistein on the simultaneous calcium-tension curves induced by levobupivacaine was examined. The effects of GF109203X, genistein, PD98059 and extracellular signal-regulated kinase (ERK) siRNA on levobupivacaine-induced caldesmon phosphorylation were investigated. The effect of genistein on the ERK and tyrosine phosphorylation induced by levobupivacaine was examined. The effect of GF109203X, PD98059, Y-27632, SP600125, and ML-7 HCl on the levobupivacaine-induced phosphorylation of CPI-17 and MLC 20 were investigated. Genistein, tyrphostin 23, GF109203X, PD98059, Y-27632, ML-7 HCl, and 1-butanol attenuated levobupivacaine-induced contraction. Genistein caused a right downward shift of the calcium-tension curves induced by levobupivacaine. Genistein attenuated levobupivacaine-induced phosphorylation of protein tyrosine, ERK and caldesmon. PD98059, ERK siRNA and GF109203X attenuated levobupivacaine-induced caldesmon phosphorylation. GF109203X, Y-27632, SP600125, ML-7 HCl and PD98059 attenuated CPI-17 phosphorylation and MLC 20 phosphorylation induced by levobupivacaine. These results suggest that levobupivacaine-induced caldesmon phosphorylation contributing to levobupivacaine-induced contraction is mediated by a pathway involving ERK, which is activated by tyrosine kinase or protein kinase C (PKC). The phosphorylation of CPI-17 and MLC 20 induced by levobupivacaine is mediated by cellular signaling pathways involving PKC, Rho-kinase, and c-Jun NH 2 -terminal kinase or PKC, Rho-kinase, ERK, and myosin light chain kinase. [ABSTRACT FROM AUTHOR]

Background: Atypical fibroxanthomas (AFXs) and pleomorphic dermal sarcomas (PDSs) are UV‐induced pleomorphic skin tumors with a non‐specific immunoprofile. For that reason, exclusion of other dedifferentiated tumor entities by immunohistochemistry is still mandatory to avoid misdiagnosis. Methods: We determined the expression frequency of several melanocytic and myofibroblastic markers investigating 50 AFXs and PDSs.. Next‐generation‐sequencing (NGS) was performed in microphthalmia‐associated transcription factor (MiTF)‐expressing cases. Results: We identified one MiTF‐expressing AFX and PDS, and two PDSs harboring single S100‐positive dendritic cells whereas Melan A, HMB45, and SOX10 were negative. Calponin was moderately expressed by tumor giant cells in one PDS whereas h‐caldesmon, desmin, and myogenin were not expressed in any of the AFXs or PDSs. The MiTF‐positive AFX presented CDKN2A, OXA1L, and PDGFRA mutations whereas the PDS harbored a typical TP53 mutation. Both patients have not shown any tumor progression over the last 16 and 30 months. Conclusion: Rarely, AFX and PDS express the melanocytic marker MiTF and/or the myofibroblastic marker calponin. In doubtful cases, using a panel of immunohistochemical markers helps to avoid misdiagnosis. [ABSTRACT FROM AUTHOR]

Highlights • IFN-γ induces biphasic changes in caldesmon structure, AJ organization and expression. • IFN-γ induces caldesmon redistribution from the cell periphery to the cytoplasm. • IFN-γ induces AJ redistribution, decreases AJ junctional areas and protein expression. • IFN-γ affects caldesmon-actin and caldemon-myosin complexes. • p38 MAP kinase is not a key regulator that governs the IFN-γ-induced cellular changes. Abstract Endothelial barrier dysfunction leads to increased endothelial permeability and is an early step in the development of vascular inflammatory diseases such as atherosclerosis. Interferon-γ (IFN-γ), a proinflammatory cytokine, is known to cause increased endothelial permeability. However, the mechanisms by which IFN-γ disrupts the endothelial barrier have not been clarified. This study aimed to investigate how IFN-γ impairs the endothelial barrier integrity by specifically examining the roles of caldesmon, adherens junctions (AJs) and p38 mitogen-activated protein (MAP) kinase in IFN-γ-induced endothelial barrier dysfunction. IFN-γ exhibited a biphasic effect on caldesmon localization and both the structural organization and protein expression of AJs. In the early phase (4-8 h), IFN-γ induced the formation of peripheral caldesmon bands and discontinuous AJs, while AJ protein expression was unchanged. Interestingly, IFN-γ also stimulated caldesmon phosphorylation, resulting in actin dissociation from caldesmon at 8 h. Conversely, changes seen in the late phase (16–24 h) included cytoplasmic caldesmon dispersal, AJ linearization and junctional area reduction, which were associated with reduced membrane, cytoskeletal and total AJ protein expression. In addition, IFN-γ enhanced myosin binding to caldesmon at 12 h and persisted up to 24 h. Furthermore, inhibition of p38 MAP kinase by SB203580 did not reverse either the early or late phase changes observed. These data suggest that IFN-γ may activate signaling molecules other than p38 MAP kinase. In conclusion, our findings enhance the current understanding of how IFN-γ disrupts endothelial barrier function and reveal potential therapeutic targets, such as caldesmon and AJs, for the treatment of IFN-γ-associated vascular inflammatory diseases. [ABSTRACT FROM AUTHOR]

Non-muscle caldesmon (l-CaD) is involved in the regulation of actin cytoskeletal remodeling in the podosome formation, but its function in osteoclastogenesis remains to be determined. In this study, RANKL-induced differentiation of RAW264.7 murine macrophages to osteoclast-like cells (OCs) was used as a model to determine the physiological role of l-CaD and its phosphorylation in osteoclastogenesis. UponRANKL treatment, RAW264.7 cells undergo cell-cell fusion into multinucleate, and TRAP-positive large OCs with a concomitant increase of l-CaD expression. Using gain- and loss-of-function in OC precursor cells followed by RANKL induction, we showed that the expression of l-CaD in response to RANKL activation is an important event for osteoclastogenesis, and bone resorption. To determine the effect of l-CaD phosphorylation in osteoclastogenesis, three decoy peptides of l-CaD were used with, respectively, Ser-to-Ala mutations at the Erk- and Pak1-mediated phosphorylation sites, and Ser-to-Asp mutation at the Erk-mediated phosphorylation sites. Both the former two peptides competed with the C-terminal segment of l-CaD for F-actin binding and accelerated formation of podosome-like structures in RANKL-induced OCs, while the third peptide did not significantly affect the F-actin binding of l-CaD, and decreased the formation of podosome-like structures in OCs. With the experiments using dephosphorylated and phosphorylated l-CaD mutants, we further showed that dephosphorylated l-CaD mutant facilitated RANKL-induced TRAP activity with an increased cell fusion index, whereas phosphorylated l-CaD decreased the TRAP activity and cell fusion. Our findings suggested that both the level of l-CaD expression and the extent of l-CaD phosphorylation play a role in RANKL-induced osteoclast differentiation. [ABSTRACT FROM AUTHOR]

The cover page of the issue is presented, along with subscription information, editors and the table of contents.

Background: We sought to compare the sensitivity and specificity of 2 different caldesmon antibodies in differentiating leiomyosarcoma from other cutaneous spindle cell neoplasms. Methods: Representative cutaneous spindle cell neoplasms were identified, including leiomyosarcoma, atypical fibroxanthoma, dermatomyofibroma and spindle cell squamous cell carcinoma. Immunohistochemistry was performed with antibodies directed toward caldesmon, smooth‐muscle actin (SMA) and desmin. Sensitivity and specificity were calculated using grades from 3 independent observers. Results: The sensitivity of caldesmon (Ventana) was 100% (95% CI 78.2%‐100%) and the specificity was 8.3% (2.8%‐18.4%). Because this stain appeared to be non‐specific, additional testing was performed on the same set of specimens using a second caldesmon clone (H‐caldesmon, Dako), which had a sensitivity of 53.9% (25.1%‐80.8%) and specificity of 96.6% (88.1%‐99.6%). The sensitivity and specificity of SMA were 85.7% (57.2%‐98.2%) and 84.5% (72.6%‐92.7%), respectively. The sensitivity of desmin was 53.3% (26.6%‐78.7%) with a specificity of 100% (94.0%‐100%). Conclusions: The Ventana caldesmon clone is not specific to smooth muscle, a potential pitfall to laboratories using this clone. The staining pattern, sensitivity and specificity of the Dako H‐caldesmon antibody clone are similar to results from prior studies. The sensitivity and specificity of the Dako clone support its use in smooth muscle identification as an additional marker in challenging cases. [ABSTRACT FROM AUTHOR]

Background. The presence of vessel invasion is considered indicative of a poor prognosis in many malignant tumors. We aimed to compare the sensitivity of elastin stains (van Gieson's and orcein methods) with 2 smooth muscle markers (h-caldesmon and desmin) in gastric, pancreatic, and colorectal adenocarcinoma specimens. Materials and Methods. We used 27 (29.3%) gastric, 35 (38.0%) pancreatic, and 30 (32.6%) colorectal resection specimens. We applied a provisional classification of vessel invasion patterns: type A, a focus with a nearby artery unaccompanied by a vein; type T, a focus at the invasive front without an unaccompanied artery; and type X, foci that only appeared by any of the 4 stains used. Results. There were 369 foci. The smooth muscle markers were more sensitive than the elastin stains, and h-caldesmon more sensitive than desmin, in all types. Among the 139 type A foci, 33 (23.7%) were positive by desmin and h-caldesmon, whereas the elastin stains were not (P = .001). h-Caldesmon was the only positive marker in 11 (7.9%; P = .011). Among the 78 type T foci, 21 (26.9%) were positive by desmin and h-caldesmon, when both elastin stains were negative (P = .000). In 16 (20.5%) foci, h-caldesmon was the only positive marker (P = .002). Among 152 type X foci, 91 (59.9%) were positive by all markers, 26 (17.1%) by both desmin and h-caldesmon, and 9 (5.9%) by only the 2 elastin stains (P = .001). Conclusion. We recommend these stains for suspect foci in gastric, pancreatic, and colorectal adenocarcinoma specimens. They might highlight both predictable and unpredictable foci. [ABSTRACT FROM AUTHOR]

Based on an electron microscopic immunocytochemical study of the body wall musculature in a Gordian worm, the three regulatory muscle proteins troponin, calponin and caldesmon appear to be present. Given that no caldesmon homolog has been identified in the genome of invertebrates to date, the result seemed surprising. Moreover, troponin and calponin/caldesmon should exclude each other. However, in view of the fact that troponin has recently also been found in non-striated invertebrate muscle and the smooth muscle proteins calponin and closely related proteins can occur in invertebrate oblique muscle types, it seems possible that in the body wall of Gordian worms a muscle type occurs that combines the features of smooth and striated muscle. Similarities to the Caenorhabditis elegans muscle underscore the phylogenetic relationship between the ecdysozoan phyla Nematoda and Nematomorpha. [ABSTRACT FROM AUTHOR]

Primary leiomyosarcoma arising from the ovarian vein is extremely rare, with only 10 cases reported in the literature. We report on a case of leiomyosarcoma of the left ovarian vein in a 67-year-old woman who presented with abdominal discomfort. Pelvic ultrasound revealed a large, solid, irregular mass in close relation to the left ovary. The patient subsequently underwent a total hysterectomy with bilateral salpingo-oophorectomy. Histologically, the tumor was composed of interlacing fascicles of spindle cells with abundant eosinophilic cytoplasm, hyperchromatic nuclei, and prominent nucleoli. Mitotic activity was high, with 24 mitoses in 10 high-power fields. Areas of necrosis and hemorrhage were present within the tumor. Immunohistochemically, the tumor cells showed diffuse immunoreactivity for vimentin, muscle-specific actin, desmin, and caldesmon. The patient received chemotherapy postoperatively but subsequently developed disseminated metastatic disease (lung, liver, iliac lymph nodes, and peritoneum). Primary leiomyosarcomas arising from the ovarian vein are aggressive neoplasms, and the prognosis correlates with stage. [ABSTRACT FROM AUTHOR]

Uterine smooth muscle tumours with distinctive epithelioid smooth muscle cells are called as epithelioid leiomyoma or leiomyoblastoma as the cells resemble smooth muscle cells of foetal uterus. We report a case of epitheliod leiomyoma of uterus in a South Indian peri-menopausal female. Pathological examination showed a single sub-serosal fundal mass measuring 15 x 14 x 10 cm in diameter. Cut section of the mass showed soft to firm grey white areas along with cystic spaces. Microscopy revealed sheets and peri-theliomatous arrangement of round to polygonal cells with eosinophilic cytoplasm and vesicular nucleus. Immunohistochemically, the polygonal cells stained strongly and positively with Smooth Muscle Actin (SMA) and desmin and negative for HMB-45 stain. The Ki-67 proliferative index was less than 1%.

Aim: In this study, we attempted to identify the proteins involved in aggressive periodontitis and chronic periodontitis associated with neutrophil chemotaxis dysfunction. Material and Methods: method were examined in neutrophils from four types of subjects using the real-time polymerase chain reaction: twenty patients suffering from aggressive periodontitis with or without the dysfunction, 15 patients with chronic periodontitis, and 15 controls. A two-dimensional fluorescence difference gel electrophoresis system was used to detect differences in protein expression between neutrophils from four patients suffering from aggressive periodontitis combined with neutrophil chemotaxis dysfunction and those from four controls. Results: Four proteins, displayed a higher protein expression level in the neutrophils from the patients suffering from aggressive periodontitis combined with the neutrophil dysfunction than in those from the control group. The caldesmon mRNA levels in the neutrophils from the patients suffering from aggressive periodontitis combined with the neutrophil dysfunction were high compared with those in the neutrophils from the patients suffering from the other two types of periodontitis and those from the control group. Conclusion: The levels of protein production in neutrophils from aggressive periodontitis patients with the dysfunction were higher than those in neutrophils from the control group. In particular, caldesmon is a candidate marker of aggressive periodontitis combined with neutrophil chemotaxis dysfunction.

We show here that chicken gizzard caldesmon (CaD) and its C-terminal domain (residues 636–771, CaD136) are intrinsically disordered proteins. The computational and experimental analyses of the wild type CaD136 and series of its single tryptophan mutants (W674A, W707A, and W737A) and a double tryptophan mutant (W674A/W707A) suggested that although the interaction of CaD136 with calmodulin (CaM) can be driven by the non-specific electrostatic attraction between these oppositely charged molecules, the specificity of CaD136-CaM binding is likely to be determined by the specific packing of important CaD136 tryptophan residues at the CaD136-CaM interface. It is suggested that this interaction can be described as the “buttons on a charged string” model, where the electrostatic attraction between the intrinsically disordered CaD136 and the CaM is solidified in a “snapping buttons” manner by specific packing of the CaD136 “pliable buttons” (which are the short segments of fluctuating local structure condensed around the tryptophan residues) at the CaD136-CaM interface. Our data also show that all three “buttons” are important for binding, since mutation of any of the tryptophans affects CaD136-CaM binding and since CaD136 remains CaM-buttoned even when two of the three tryptophans are mutated to alanines.

Background: Myopericytoma is reported to occur mainly in the skin and superficial soft tissue of the extremities. In contrast, occurrence in the urinary bladder is extremely rare.Case Presentation: We describe a 75-year-old Japanese man who developed a submucosal tumor at the right trigone of his bladder that led to interference with the discharge of right ureteral calculus. No invasive growth was observed by magnetic resonance imaging. Transurethral resection was successfully performed; histopathological analysis revealed perivascular proliferation of spindle-shaped to oval-shaped, cytologically bland tumor cells with eosinophilic cytoplasm. On immunohistochemical examination, the tumor cells were positive for alpha-smooth muscle actin, desmin, CD34 and h-caldesmon.Conclusion: Cystoscopic and pathological findings were compatible with a diagnosis of myopericytoma of the urinary bladder. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle (VSM) is unique in its ability to maintain an intrinsic level of contractile force, known as tone. Vascular tone is believed to arise from the constitutive activity of membrane-bound L-type Ca2+ channels (LTCC). This study used a pharmacological agonist of LTCC, Bay K8644, to elicit a sustained, sub-maximal contraction in VSM that mimics tone. Downstream signaling was investigated in order to determine what molecules are responsible for tone. Medial strips of swine carotid artery were stimulated with 100 nM Bay K8644 to induce a sustained level of force. Force and phosphorylation levels of myosin light chain (MLC), MAP kinase, MYPT1, CPI-17, and caldesmon were measured during Bay K8644 stimulation in the presence and absence of nifedipine, ML-7, U0126, bisindolylmaleimide (Bis), and H-1152. Nifedipine and ML-7 inhibited force and MLC phosphorylation in response to Bay K8644. Inhibition of Rho kinase (H-1152) but not PKC (Bis) inhibited Bay K8644 induced force. U0126 significantly increased Bay K8644-dependent force with no effect on MLC phosphorylation. Neither CPI-17 nor caldesmon phosphorylation were increased during the maintenance of sustained force. Our results suggest that force due to the influx of calcium through LTCCs is partially MLC phosphorylation-dependent but does not involve PKC or caldesmon. Interestingly, inhibition of MLC kinase (MLCK) and PKC significantly increased MAP kinase phosphorylation suggesting that MLCK and PKC may directly or indirectly inhibit MAP kinase activity during prolonged contractions induced by Bay K8544. [ABSTRACT FROM AUTHOR]

In early studies on smooth muscle, I described a crude myosin fraction (CMF) in which self-assembly of myosin filaments was observed. For the first time, the 14-nm periodicity stemming from regular arrangement of myosin heads on the filament surface was observed (Sobieszek in J Mol Biol 70:741-744, 1972). In this fraction, we also observed formation of long ribbon-shaped aggregates exhibiting a 5.6-nm periodicity, characteristic of tropomyosin (TM) paracrystals (Sobieszek and Small in Phil Trans R Soc Lond B 265:203-212, 1973). We therefore concluded that these ribbons were made of TM and they might be related to the myosin ribbons observed in electron micrographs (EM) of intact smooth muscle (Lowy and Small in Nature 227:46-51, 1970; Small and Squire in Mol Biol 67:117-149, 1972). Subsequently, Small (J Cell Sci 24:327-349, 1977) concluded that the ribbons observed in the EM sections were an artifact, but their observation in the CMF was not addressed. I have now revisited two aspects of the above studies. Firstly, based on my new multi-angle laser-scattering data and considering the length and stability of the building unit for the filament, a myosin trimer fit better to the previously proposed helical structure. Secondly, after two decades of systematic examinations of protein compositions in multiple smooth muscle extracts and isolated filaments, I concluded that the ribbons were made of caldesmon and not TM. Thirdly, actin-activated ATPase activity measurements indicated that modulation of this activity (by CaD and TM) was synergistic, cooperative and depended on myosin to actin ratio. [ABSTRACT FROM AUTHOR]

Extrauterine endometrial stromal sarcomas (ESSs) are quite rare tumors, and vagina is an unusual site for these tumors. This paper presents a very rare pathological entity of primary vaginal ESS. A 46-year-old woman with a complaint of postcoital vaginal bleeding, low abdominal pain, and constipation was admitted to the clinic. She had a mass of seven cm in size, located in the posterior fornix detected on physical examination. The preoperative biopsy showed ESS, surgical material, and evaluation of an endometrium confirmed the diagnosis of primary vaginal ESS. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial vaginectomy. The diagnosis of ESS performed by pathologic and immunohistochemical evaluation was: caldesmon (-), actin (-), desmin (-). CD10 (+), ER (+), PR (+), and vimentin (+). There was no ESS lesion in the endometrium. The patient was free of tumor for 22 months after the surgery without any additional therapy. In this study, the authors report the sixth case of primary vaginal ESS in the literature and aim to discuss diagnostic criteria and management protocols in the light of the literature. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle contraction is primarily regulated by phosphorylation of myosin light chain. There are also modulatory pathways that control the final level of force development. We tested the hypothesis that protein kinase C (PKC) and mitogen-activated protein (MAP) kinase modulate vascular smooth muscle activity via effects on MAP kinase phosphatase-1 (MKP-1). Swine carotid arteries were mounted for isometric force recording and subjected to histamine stimulation in the presence and absence of inhibitors of PKC [bisindolylmaleimide-1 (Bis)], MAP kinase kinase (MEK) (U0126), and MKP-1 (sanguinarine) and flash frozen for measurement of MAP kinase, PKC-potentiated myosin phosphatase inhibitor 17 (CPI-17), and caldesmon phosphorylation levels. CPI-17 was phosphorylated in response to histamine and was inhibited in the presence of Bis. Caldesmon phosphorylation levels increased in response to histamine stimulation and were decreased in response to MEK inhibition but were not affected by the addition of Bis. Inhibition of PKC significantly increased p42 MAP kinase, but not p44 MAP kinase. Inhibition of MEK with U0126 inhibited both p42 and p44 MAP kinase activity. Inhibition of MKP-1 with sanguinarine blocked the Bis-dependent increase of MAP kinase activity. Sanguinarine alone increased MAP kinase activity due to its effects on MKP-1. Sanguinarine increased MKP-1 phosphorylation, which was inhibited by inhibition of MAP kinase. This suggests that MAP kinase has a negative feedback role in inhibiting MKP-1 activity. Therefore, PKC catalyzes MKP-1 phosphorylation, which is reversed by MAP kinase. Thus the fine tuning of vascular contraction is due to the concerted effort of PKC, MAP kinase, and MKP-1. [ABSTRACT FROM AUTHOR]

Primary cutaneous leiomyosarcoma (PCL) is an exceedingly uncommon malignant superficial soft tissue sarcoma with a predilection for middle-aged to elderly male. Morphologic differential diagnosis includes a host of other malignant spindle cell neoplasms, thereby necessitating the use of a panel of immunohistochemical markers to arrive at a definitive diagnosis. We report a case of PCL arising in the right leg of a 70-year-old male.

Muscles of bivalve molluscs have double calcium regulation — myosin-linked and actin-linked. While the mechanism of myosin-linked regulation is sufficiently studied, there is still no consensus on the mechanism of actin-linked regulation. Earlier we showed a high degree of Ca 2 + -sensitivity of thin filaments from the adductor muscle of the mussel Crenomytilus grayanus (Mytiloida). In order to elucidate the nature of this regulation, we isolated the fraction of minor proteins from the mussel thin filaments, which confers Ca 2 + -sensitivity to reconstituted actomyosin–tropomyosin. Proteins of this fraction, ABP-19, ABP-20, and ABP-28, were chromatographically purified and identified. According to the results of mass spectrometry and Western blot analysis, as well as by their functional properties, these mussel actin-binding proteins appeared to correspond to the troponin components from the skeletal muscles of vertebrates (TnC, TnI and TnT). The reconstituted mussel troponin complex confers to actomyosin–tropomyosin more than 80% Ca 2 + -sensitivity. The in vivo molar ratio of actin/tropomyosin/troponin was calculated to be 7:1:0.5, i.e., the content of troponin in mussel thin filaments is two times lower than in thin filaments of skeletal muscles of vertebrates. These data demonstrate that troponin-like regulation found in the catch muscle of the mussel C. grayanus is present at least in two suborders of bivalves: Pectinoida and Mytiloida. [ABSTRACT FROM AUTHOR]

Glomus tumors showing nuclear pleomorphism without any other malignant features have been defined as symplastic glomus tumors. This type of glomus tumor is rarely encountered. Another case of symplastic glomus tumor is described in this study. A 37-year-old woman referred to the hospital with the complaint of a palpable tender nodule on the fourth finger tip of her left hand. The lesion had been present for about a year and aggravation of tenderness upon cold exposure was conspicuous. It was a 0.5 cm well circumscribed lesion with round to cuboidal epithelioid cells showing high grade nuclear pleomorphism. Nests of cells more uniform in shape and showing punched out nucleus representative of typical glomus tumor could also be observed. Immunohistochemical study showed expression of smooth muscle actin, caldesmon and vimentin. Ki-67 labeling index was undetectable. Investment of tumor cells was shown by type IV collagen. In contrast to its atypical cellular morphology, symplastic glomus tumor clinically behaves benign, and it is important to differentiate it from malignant glomus tumor as well as other primary or metastatic malignant tumors. [ABSTRACT FROM AUTHOR]

Smooth muscle in the pulmonary artery of PAH subjects, both idiopathic and hereditary, is characterized by hyperplasia. Smooth muscle cells (HPASMC) isolated from subjects with or without PAH retain their in vivo phenotype as illustrated by their expression of alpha-smooth muscle actin and expression of H-caldesmon. Both non PAH and PAH HPASMC display a lengthy, approximately 94h, cell cycle. The HPASMC from both idiopathic and hereditary PAH display an abnormal proliferation characterized by continued growth under non-proliferative, non-growth stimulated conditions. This effector independent proliferation is JNK and p38 MAP kinase dependent. Blocking the activation of either abrogates the HPASMC growth. HPASMC from non PAH donors under quiescent conditions display negligible proliferation but divide upon exposure to growth factors such as PDGF-BB or FGF2 but not EGF. This growth does not involve the MAP kinases. Instead it routes via the tyrosine kinase receptor through mTOR and then 6SK. In the PAH cells PDGF-BB and FGF2 augment the dysregulated cell proliferation, also through mTOR/6SK. Additionally, blocking the activation of mTOR also modulates the MAP kinase promoted dysregulated growth. These results highlight key alterations in the growth of HPASMC from subjects with PAH which contribute to the etiology of the disease and can clearly be targeted at various regulatory points for future therapies. [ABSTRACT FROM AUTHOR]