Evaluation of Use of Adipose Cells in Various Procedures of Plastic Surgery and its Volumetric Quantification using High Resolution Ultrasound.

INTRODUCTION: Autologous fat transfer is based on one of the principles of plastic surgery, replace like with like. It is used in wide variety of aesthetic procedures such as lip, facial augmentation and reconstructive procedures such as involutional disorders, post traumatic defects etc. AIM: This prospective study was on the use of adipose cells in various procedures of plastic surgery, the role of high resolution ultrasound in estimating the volume of the grafted fat, comparison of the results based on the different donor sites of the harvested fat and comparison of the effectiveness of grafted fat in extremities and craniofacial region. MATERIALS AND METHODS: In this prospective study a total of 34 patients underwent fat grafting procedure at various sites of the body from May 2012 till November 2013. After noting the details of the patient, details of the defect, laboratory and radiological investigations, the consent for the fat grafting procedure was taken. Clinical photographs and High Resolution Ultrasound (HRUS) volume estimation was done on a regular basis as per the protocol. RESULTS: Out of 34 patients, 29 patients underwent free fat grafting and five patients underwent derma fat grafting. HRUS at six months revealed a mean 73.5% and 63.5% of the injected fat remained in contour deformity in extremities and craniofacial region respectively. HRUS at one year revealed a mean 57.4% and 41.4% of the injected fat remained in contour deformity in extremities and craniofacial region respectively. CONCLUSION: HRUS is an excellent handy modality for serial volume estimation, cost-effective, non-invasive, multi planar modality, does not require any preparation, and easily done outdoor procedure. Follow up is a practical proposition. Autologous fat grafting is a safe procedure with no significant complications other than fat reabsorption and it can be done under local anaesthesia in contour deformity of smaller areas. Disadvantage of autologous fat grafting is the fat reabsorption needing multiple sittings.

Dynamic article: composite antropyloric valve and gracilis muscle transposition for total anorectal reconstruction: a preliminary report.

BACKGROUND: Technique and functional outcomes of anorectal reconstruction using an antropyloric graft have been reported previously. This technique had reasonable initial outcomes but lacked voluntary function. OBJECTIVE: We hereby report the initial results of patients who underwent gracilis muscle wrapping around the perineally transposed antropyloric valve in an attempt to improve voluntary fecal control. SETTING: This study was conducted at a single tertiary care institution. PATIENTS: Eight adult patients (7 men and 1 woman) with a median age of 38 years (range, 19-51 years) underwent this procedure. Seven patients already had anorectal reconstruction with a transposed antropyloric valve, and 1 patient with severely damaged anal sphincter complex underwent single-stage composite antropylorus transposition with a gracilis muscle wrap. MAIN OUTCOME MEASURES: The primary outcome measures were anatomical integrity and functional status of the composite graft in the perineum. RESULTS: No operative mortality or serious procedure-related morbidity occurred in any patient. The median postoperative resting pressure was 29 mmHg (range, 22-38 mmHg) and squeeze pressure was 72.5 mmHg (range, 45-267 mmHg). There was a significant improvement in the squeeze pressure following surgery (p = 0.039). Also, the St. Mark's incontinence scores significantly improved in all patients and varied between 7 and 9 (p = 0.003). The ability to defer defecation and the reduced frequency of leakage accidents were the prime reasons for improved postgraciloplasty outcomes in these patients. On personal interviews, all patients who underwent this procedure were satisfied with the results of their surgery. LIMITATIONS: A longer follow-up with a larger sample size is required. Quality-of-life data have not been evaluated in this study. CONCLUSIONS: Gracilis muscle wrapping around a perineally transposed antropyloric valve is possible and improves the voluntary control and overall functional outcomes in a select group of patients with end-stage fecal incontinence requiring anal replacement (Supplemental Digital Content 1, http://links.lww.com/DCR/A173).

Basonuclin-1 modulates epithelial plasticity and TGF-ß1-induced loss of epithelial cell integrity.

Transforming growth factor-ß1 (TGF-ß1) is a multifunctional cytokine and critically involved in the progression of a variety of cancers. TGF-ß1 signaling can impair tumor development by its anti-proliferative and pro-apoptotic features. In contrast, it may actively promote tumor progression and cancer cell dissemination by inducing a gradual switch from epithelial towards mesenchymal-like cell features (EMT-like), including decreased intercellular adhesion. Here, we show that expression of the transcription factor Basonuclin-1 (Bnc1) modulates TGF-ß1-induced epithelial dedifferentiation of mammary epithelial cells. RNAi-mediated repression of Bnc1 resulted in enhanced intercellular adhesion and strongly impaired TGF-ß1-dependent sheet disintegration and cell scattering. In contrast, forced expression of Bnc1 modifies plasma membrane/cytoskeletal dynamics and seemingly interferes with the initiation of sustainable cell-cell contacts. Follow-up analyses revealed that Bnc1 affects the expression of numerous TGF-ß1-responsive genes including distinct EMT-related transcription factors, some of which modulate the expression of Bnc1 themselves. These results suggest that Bnc1 is part of a transcription factor network related to epithelial plasticity with reciprocal feedback-loop connections on which Smad-factors integrate TGF-ß1 signaling. Our study demonstrates that Bnc1 regulates epithelial plasticity of mammary epithelial cells and influences outcome of TGF-ß1 signaling.

Teaching neuroimages: neurocysticercosis with subretinal cyst.

A 30-year-old woman presented with headache and diminution of vision of 2 weeks' duration. Visual acuity was finger counting at 1 meter in the right eye. Fundus examination showed a subretinal cyst (figure 1A). Neurologic examination was normal. Neuroimaging revealed neurocysticercosis (figure 2A). Ultrasound orbit showed subretinal cysticercosis (figure 2B). The patient was started on steroids and laser photocoagulation was recommended.

Oral ingestion of Capsaicin, the pungent component of chili pepper, enhances a discreet population of macrophages and confers protection from autoimmune diabetes.

Vanilloid receptor 1 (VR1) is expressed on immune cells as well as on sensory neurons. Here we report that VR1 can regulate immunological events in the gut in response to its ligand Capsaicin (CP), a nutritional factor, the pungent component of chili peppers. Oral administration of CP attenuates the proliferation and activation of autoreactive T cells in pancreatic lymph nodes (PLNs) but not other lymph nodes, and protects mice from development of type 1 diabetes (T1D). This is a general phenomenon and not restricted to one particular strain of mice. Engagement of VR1 enhances a discreet population of CD11b(+)/F4/80(+) macrophages in PLN, which express anti-inflammatory factors interleukin (IL)-10 and PD-L1. This population is essential for CP-mediated attenuation of T-cell proliferation in an IL-10-dependent manner. Lack of VR1 expression fails to inhibit proliferation of autoreactive T cells, which is partially reversed in (VR1(+/+) → VR1(-/-)) bone marrow chimeric mice, implying the role of VR1 in crosstalk between neuronal and immunological responses in vivo. These findings imply that endogenous ligands of VR1 can have profound effect on gut-mediated immune tolerance and autoimmunity by influencing the nutrient-immune interactions.

The Forkhead factor FoxQ1 influences epithelial differentiation.

The Forkhead family of transcription factors comprises numerous members and is implicated in various cellular functions, including cell growth, apoptosis, migration, and differentiation. In this study, we identified the Forkhead factor FoxQ1 as increased in expression during TGF-ß1 induced changes in epithelial differentiation, suggesting functional roles of FoxQ1 for epithelial plasticity. The repression of FoxQ1 in mammary epithelial cells led to a change in cell morphology characterized by an increase in cell size, pronounced cell-cell contacts, and an increased expression of several junction proteins (e.g., E-cadherin). In addition, FoxQ1 knock-down cells revealed rearrangements in the actin-cytoskeleton and slowed down cell cycle G1-phase progression. Furthermore, repression of FoxQ1 enhanced the migratory capacity of coherent mammary epithelial cells. Gene expression profiling of NM18 cells indicated that FoxQ1 is a relevant downstream mediator of TGF-ß1-induced gene expression changes. This included the differential expression of transcription factors involved in epithelial plasticity, for example, Ets-1, Zeb1, and Zeb2. In summary, this study has elucidated the functional impact of FoxQ1 on epithelial differentiation.

Quantitative tumor volume VS TNM staging: the impact on prognosis in head and neck cancer.

OBJECTIVES: To evaluate the prognostic value of tumor volume (TV) by clinical method (CM) and Computerized Tomography (CT) scan in head and neck (H and N) cancer. MATERIALS AND METHODS: Total 25 patients' (pts) pretreatment tumor volume (PT TV) was assessed clinically by cuboid volume method. Afterwards contrast enhanced computerized tomography (CECT) images of the pts were transferred to workstation by DICOM software. The computerized tomography tumor volume (CT TV) was obtained on Radworks 6.0, using mouse control cursor. After assessment, the patients were given 3 cycles of neoadjuvant chemotherapy followed by radiotherapy by conventional method on Co-60 Theratron 780 C. After 1 month of treatment, TV was again measured. STATISTICAL METHOD: Statistical analysis was done on MSTAT statistical analysis software. Two-tailed student t test, chi square test and test for two proportions for significance had been used. RESULTS: Large variations in tumor volume were found both in intra as well as inter T-stages. As the tumor size increases with T stages, the difference in measurement of TV by both methods decreases. CT TV results pre as well as post-treatment were more consistent than clinical method. CONCLUSION: The use of TV as a prognostic factor by CT scan seems to be more useful parameter than the CM. TV should be included in the TNM (tumor, node, and metastasis) classification after setting the strict guidelines for tumor delineation, to solve the discrepancy of treatment outcome in the same clinical stage.

Letrozole for brain and scalp metastases from breast cancer--a case report.

Brain metastases from breast cancer have a poor prognosis. There have been reports of patients with breast cancer and brain metastases responding well to tamoxifen therapy. We report a very unusual case of intact breast carcinoma with brain as well as scalp metastasis responding well to letrozole (aromatase inhibitor) therapy for a prolonged period of time.

Effect of risperidone on prolactinoma--a case report.

Risperidone induced galactorrhea and hyperprolactinemia have been reported but its role in the growth of prolactinoma is not yet conclusive, due to extreme rarity of such cases. We describe a woman, suffering from Bipolar Disorder-manic episode, who exhibited prolactinoma while on risperidone therapy. The withdrawal of risperidone resulted in disappearance of prolactinoma though her prolactin level remained elevated along with persistent galactorrhea. The change to olanzapine therapy did not show much change in serum prolactin level and galactorrhea. Ultimately, only adding of bromocriptine resulted in disappearance of symptoms of prolactinemia and normal serum prolactin level was achieved and galactorrhea stopped. Further study is recommended to find out relationship between the growth of prolactinoma and risperidone.

Case report. Orbital metastasis from gall bladder carcinoma.

Clinical presentation of an extraabdominal metastasis from carcinoma of the gall bladder is rare. Orbital metastasis from gall bladder carcinoma has not been previously reported. We report a case of a 40-year-old woman who developed orbital metastasis from carcinoma of the gall bladder.

An endoplasmic reticulum protein implicated in chaperoning peptides to major histocompatibility of class I is an aminopeptidase.

gp96, an abundant peptide-binding chaperone of the lumen of the endoplasmic reticulum and an acceptor of peptides transported into the endoplasmic reticulum through transporter associated with antigen processing, is shown to be an aminopeptidase. gp96 can trim an amino-terminal extended 19-mer precursor of the K(b)-binding VSV8 epitope for recognition by the cognate cytotoxic T lymphocyte clone. These observations support a role for gp96 in the amino-terminal trimming of extended peptides in the endoplasmic reticulum.

Adjuvanticity of alpha 2-macroglobulin, an independent ligand for the heat shock protein receptor CD91.

We recently have identified CD91 as a receptor for the heat shock protein gp96. CD91 was identified initially as a receptor for alpha(2)-macroglobulin (alpha(2)M). Gp96 and alpha(2)M are both ligands for CD91. Because gp96-chaperoned peptides can prime CD8(+) T cell responses and are re-presented by APCs, we tested alpha(2)M for similar properties. Our studies show that alpha(2)M binds peptides in vitro and that the peptides, chaperoned by alpha(2)M, efficiently prime peptide-specific CD8(+) T cell responses in mice immunized with alpha(2)M-peptide complexes. Furthermore, peptides chaperoned by alpha(2)M, like those chaperoned by gp96, can be re-presented by CD91(+) APCs on their MHC I molecules. These studies demonstrate that alpha(2)M molecules, like the heat shock protein molecules, are T cell adjuvants that can channel exogenous Ags into the endogenous pathway of Ag presentaion. The remarkable similarities between an intracellular chaperone and an extracellular serum chaperone may have interesting physiological ramifications.

CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin.

Complexes of the heat shock protein gp96 and antigenic peptides are taken up by antigen-presenting cells and presented by MHC class I molecules. In order to explain the unusual efficiency of this process, the uptake of gp96 had been postulated to occur through a receptor, identified recently as CD91. We show here that complexes of peptides with heat shock proteins hsp90, calreticulin, and hsp70 are also taken up by macrophages and dendritic cells and re-presented by MHC class I molecules. All heat shock proteins utilize the CD91 receptor, even though some of the proteins have no homology with each other. Postuptake processing of gp96-chaperoned peptides requires proteasomes and the transporters associated with antigen processing, utilizing the classical endogenous antigen presentation pathway.

The immunoprotective MHC II epitope of a chemically induced tumor harbors a unique mutation in a ribosomal protein.

CD4(+) T lymphocyte clones, generated from mice immunized with the methylcholanthrene-induced fibrosarcoma Meth A (H-2(d)), are restricted by I-E(d) and recognize a unique antigen on Meth A. The antigen has been purified and characterized as the ribosomal protein L11. The antigenic epitope is contained within the sequence EYELRKHNFSDTG and is generated by substitution of Asn by His (italic) caused by a single point mutation. The tumor contains the wild-type and the mutated alleles. Immunization of BALB/cJ mice with the mutated epitope but not with the wild-type epitope protects mice against a subsequent challenge with the Meth A sarcoma. Adoptive transfer of CD4(+) clones into BALB/c mice renders the mice specifically resistant to Meth A sarcoma. The mutated L11 epitope is thus shown to be an immunoprotective epitope in vivo by several criteria.

Heat shock protein-chaperoned peptides but not free peptides introduced into the cytosol are presented efficiently by major histocompatibility complex I molecules.

The studies reported here bear on the events in the cytosol that lead to trafficking of peptides during antigen processing and presentation by major histocompatibility complex (MHC) I molecules. We have introduced free antigenic peptides or antigenic peptides bound to serum albumin or to cytosolic heat shock proteins hsp90 (and its endoplasmic reticular homologue gp96) or hsp70 into the cytosol of living cells and have monitored the presentation of the peptides by appropriate MHC I molecules. The experiments show that (i) free peptides or serum albumin-bound peptides, introduced into the cytosol, become ligands of MHC I molecules at a far lower efficiency than peptides chaperoned by any of the heat shock proteins tested and (ii) treatment of cells with deoxyspergualin, a drug that binds hsp70 and hsp90 with apparent specificity, abrogates the ability of cells to present antigenic peptides through MHC I molecules, and introduction of additional hsp70 into the cytosol overcomes this abrogation. These results suggest for the first time a functional role for cytosolic chaperones in antigen processing.

Heat shock proteins: the 'Swiss Army Knife' vaccines against cancers and infectious agents.

The ability of heat shock proteins to: (a) chaperone peptides, including antigenic peptides; (b) interact with antigen presenting cells through a receptor; (c) stimulate antigen presenting cells to secrete inflammatory cytokines; and (d) mediate maturation of dendritic cells, makes them a one-stop shop for the immune system. These properties also permit the utilization of heat shock proteins for development of a new generation of prophylactic and therapeutic vaccines against cancers and infectious diseases.