RESUMO
[Figure: see text].
Assuntos
Aterosclerose/enzimologia , Colesterol/metabolismo , Células Espumosas/enzimologia , Músculo Liso Vascular/enzimologia , Miócitos de Músculo Liso/enzimologia , Esterol Esterase/metabolismo , Animais , Aorta/enzimologia , Aorta/patologia , Aterosclerose/genética , Aterosclerose/patologia , Modelos Animais de Doenças , Células Espumosas/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Células RAW 264.7RESUMO
PURPOSE OF REVIEW: Smooth muscle cells (SMCs) are the major cell type in human atherosclerosis-prone arteries and take up excess lipids, thereby contributing to luminal occlusion. Here we provide a focused review on pathways by which smooth muscle cells (SMCs) can become foam cells in atherosclerosis. RECENT FINDINGS: A synthesis of recent and older investigations provides key mechanistic insights into SMC foam cell formation. LDL and other apoB-containing lipoproteins are modified by a diverse array of oxidative, enzymatic, and nonenzymatic processes present in the arterial intima. These modifications of LDL all promote the aggregation of LDL (agLDL), a key finding from analysis of arterial lesion particles. Scavenger receptor and phagocytic capacity of SMCs can vary greatly, perhaps related to differences in SMC phenotype or in-vitro cell culture environments, and can be increased with exposure to cytokines, growth factors, and cholesterol. Macrophages promote the formation of SMC foam cells in direct or indirect co-culture models. SUMMARY: SMCs contribute significantly to the foam cell population in atherosclerosis. Further investigation and identification of key mechanisms of SMC foam cell formation will help drive new therapeutics to reduce cardiovascular disease.
Assuntos
Aterosclerose/metabolismo , Células Espumosas/metabolismo , Lipoproteínas LDL/metabolismo , Miócitos de Músculo Liso/metabolismo , Túnica Íntima/metabolismo , Animais , Apolipoproteínas B/genética , Apolipoproteínas B/metabolismo , Aterosclerose/genética , Aterosclerose/patologia , Diferenciação Celular , Técnicas de Cocultura , Citocinas/farmacologia , Células Espumosas/efeitos dos fármacos , Células Espumosas/patologia , Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Lipoproteínas LDL/genética , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Fagocitose , Agregados Proteicos/efeitos dos fármacos , Receptores Depuradores/genética , Receptores Depuradores/metabolismo , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/patologiaRESUMO
CASE PRESENTATION: A 52-year-old woman with no significant medical history was referred to our hospital for expedited workup of progressive dysarthria and ataxia over the past year. Prior CT angiography of the head and neck showed no relevant neurologic findings but did reveal miliary lesions in the lung apices, which was later confirmed via dedicated CT chest scan (Fig 1). Review of systems was negative for any respiratory, constitutional, or rheumatologic symptoms, except for new xanthelasma-like lesions over her forehead. She previously had smoked with 20 pack-years and had no TB risk factors. MRI of the face showed a 21-mm mass within the left external temporal fascia. MRI of the head showed diffuse leptomeningeal enhancement, right frontal lobe enhancement, and cerebellar and brainstem T2/fluid-attenuated inversion recovery hyperintensity, which prompted her admission to hospital.
Assuntos
Ataxia Cerebelar , Disartria , Humanos , Feminino , Pessoa de Meia-Idade , Pulmão/patologia , Tomografia Computadorizada por Raios X , PescoçoRESUMO
Bladder cancer is a heterogeneous disease classified into two broad molecular subtype categories, basal and luminal, with critical treatment and prognostic implications. Recent studies have shown the utility of immunohistochemistry in predicting bladder cancer molecular subtypes, with a two-marker approach using GATA3 and CK5/6 showing over 80% reliability. In the current study, we calculated the accuracy of uroplakin II (UPII), a marker of urothelial differentiation, with different scores (0: <1%, 1+: 1-10%, 2+: 10-50%, 3+: >50%) to predict RNA-based luminal versus basal subtypes in a cohort of muscle-invasive bladder cancer-received neoadjuvant chemotherapy followed by radical cystectomy. The 1% cutoff of the UPII stain predicts the luminal subtype with the sensitivity and specificity of 95% and 56%, respectively. With a UPII cutoff of 10%, the sensitivity and specificity were 93% and 81%, respectively, and with a UPII cutoff of 50%, the sensitivity and specificity were 91% and 96%, respectively. The prediction performance of UPII was better than either GATA3 or CK5/6. There was no significant difference in prognoses between UPII 0-2+ and UPII 3+ patients in this cohort. The current study shows that evaluating the staining proportion score of UPII can accurately predict basal and luminal subtypes of muscle-invasive bladder cancer.
Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Uroplaquina II , Biomarcadores Tumorais , Carcinoma de Células de Transição/patologia , Humanos , Músculos/patologia , RNA , Reprodutibilidade dos Testes , Neoplasias da Bexiga Urinária/patologiaRESUMO
A 20-year-old woman presented with abdominal pain and MRI findings of intussusception of the distal small bowel with no identifiable lead point and no visualisation of the appendix. A diagnostic laparoscopy succeeded in manually reducing the intussusception but was unable to find any candidate lead point. Intraoperatively, hyperperistalsis was observed throughout the small bowel which seemed prone to transient intussusception. Incidental appendectomy revealed an uninflamed appendix with Enterobius vermicularis (pinworm) infestation, the most common parasite present in appendectomy specimens worldwide. Although intussusception in young adults is an uncommon occurrence, the unique nature of this case is amplified by the concurrent finding of E. vermicularis infection of the appendix in an adolescent in western Canada, a phenomenon normally observed in paediatric populations with higher incidence in tropical areas. Although the mechanism of intussusception in this patient remains unclear, it is hypothesised that E. vermicularis colonisation acted as an irritant stimulating intestinal hypercontractility with resulting intussusception. Successful medical eradication of the pinworm in this individual may prevent future recurrence.