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1.
J Shoulder Elbow Surg ; 33(2): 234-246, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37844830

RESUMO

BACKGROUND: Prior rotator cuff disease natural history studies have focused on tear-related factors that predict disease progression within a given shoulder. The purpose of this study was to examine both patient- and tear-related characteristics of a painful rotator cuff tear that predict future pain development and functional impairment in a shoulder with a contralateral asymptomatic cuff tear. METHODS: This was a prospective longitudinal cohort study of patients aged ≤65 years who underwent surgery for a painful degenerative rotator cuff tear and possessed an asymptomatic contralateral tear. Patients were followed up prospectively by shoulder ultrasound, physical examination, and functional score assessment. The primary outcome was change in the American Shoulder and Elbow Surgeons (ASES) score at 2 years. Secondary outcomes included the Western Ontario Rotator Cuff Index (WORC) score, Patient-Reported Outcomes Measurement Information System (PROMIS) score, Hospital Anxiety Depression Scale (HADS) depression and anxiety scores, and Veterans RAND-12 (VR-12) mental component score (MCS). RESULTS: Sixty-five patients were included, with a mean follow-up period of 37 months (range, 24-42 months). In 17 patients (26%), contralateral shoulder pain developed at a median of 15.2 months (interquartile range [IQR], 10.5 months). No difference in age, sex, Charlson Comorbidity Index, or occupational demand was noted between patients in whom pain developed and those in whom pain did not develop. In the presenting painful shoulder, there was no difference in baseline tear size, muscle degeneration, or biceps pathology between groups. The mean baseline tear length (8.6 mm vs. 3.8 mm, P = .0008) and width (8.4 mm vs. 3.2 mm, P = .0004) were larger in asymptomatic shoulders in which pain subsequently developed compared with those in which pain did not develop. However, there was no difference in mean tear enlargement (P = .51 for length and P = .90 for width). There were no differences in baseline ASES, WORC, Patient-Reported Outcomes Measurement Information System (PROMIS), or HADS depression and anxiety scores between shoulders in which pain developed and those in which pain did not develop; however, patients in whom pain developed reported a lower baseline VR-12 MCS (53.3 vs. 57.6, P = .04). Shoulders in which pain developed had higher visual analog scale pain scores (2.9 [standard deviation (SD), 2.5] vs. 0.6 [SD, 1.0]; P = .016), lower ASES scores 75 [SD, 33] vs. 100 [SD, 11.6]; P = .001), and significant changes in all WORC scales with pain onset compared with those that remained asymptomatic. The study showed no significant difference in changes in the HADS anxiety and depression scores but found a significant increase in the VR-12 MCS in patients in whom pain developed (7.1 [interquartile range, 12.6] vs. -1.9 [interquartile range, 8.7]; P = .036). CONCLUSION: In one-quarter of patients with painful cuff tears, pain developed in a contralateral asymptomatic cuff tear that resulted in a measurable decline in function within 3 years. Our analysis showed that only the baseline tear size of the asymptomatic shoulder was predictive of pain development. There were no tear-related features of the presenting painful rotator cuff tear or indices of mental health and physical function or occupational demand that were predictive of future pain development at short-term follow-up.


Assuntos
Lacerações , Lesões do Manguito Rotador , Humanos , Lesões do Manguito Rotador/complicações , Lesões do Manguito Rotador/cirurgia , Estudos Prospectivos , Estudos Longitudinais , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/cirurgia , Ruptura , Dor de Ombro/etiologia , Dor de Ombro/complicações , Resultado do Tratamento , Artroscopia
2.
J Orthop Res ; 42(5): 934-941, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38041210

RESUMO

For atraumatic rotator cuff tears, genetics contributes to symptomatic tear risk and may influence rotator cuff healing after surgical repair. But little is known about how genetic factors influence rotator cuff tear patient characteristics at presentation. We collected saliva samples for genotyping from atraumatic rotator cuff tear patients. We examined nine single nucleotide polymorphisms (SNPs) associated with cuff tears in prior literature. We estimated associations of SNP dosage with (1) age at tear diagnosis, (2) bilateral atraumatic tear prevalence, and (3) tear size. Linear regression was used to estimate associations with diagnosis age adjusted for sex and principal components. Logistic regression and ordinal logistic regression were used to estimate associations with bilateral tear prevalence and tear size category, respectively, adjusting for age, sex, and principal components. Of 344 eligible patients, 336 provided sufficient samples for genotyping. Median age at tear diagnosis was 61, 22% (N = 74) had bilateral atraumatic tears, and 9% (N = 29) had massive tears. SNP rs13107325 in the SLC39A8 gene and rs11850957 in the STXBP6 gene were associated with younger diagnosis age even after accounting for multiple comparisons (rs13107325: -4 years, 95% CI = -6.5, -1.4; rs11850957: -2.7 years, 95% CI = -4.3, -1.1). No other significant associations were observed with diagnosis age, tear size, or bilateral tear prevalence. SLC39A8 encodes a Mn transporter. STXBP6 may play a role in inflammatory responses by altering phagocytosis and antigen presentation of monocytes and macrophages. Further research is needed to determine if genetic markers can be used alongside patient characteristics to aid in identifying optimal surgical repair candidates.


Assuntos
Lesões do Manguito Rotador , Humanos , Lesões do Manguito Rotador/genética , Lesões do Manguito Rotador/cirurgia , Manguito Rotador/cirurgia , Marcadores Genéticos , Ruptura , Cicatrização , Artroscopia
3.
J Shoulder Elbow Surg ; 32(7): 1432-1444, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37024038

RESUMO

BACKGROUND: The purpose of this prospective study is to describe the mid- to long-term natural history of untreated asymptomatic degenerative rotator cuff tears in patients 65 years and younger. METHODS: Subjects with an asymptomatic rotator cuff tear in one shoulder and a contralateral painful cuff tear aged 65 years or younger were enrolled in a previously described prospective longitudinal study. Annual physical and ultrasonographic evaluations and surveillance for pain development were performed using independent examiners for the asymptomatic shoulder. RESULTS: Two hundred twenty-nine participants (mean age 57.1 years) were followed for a median of 7.1 (range 0.3-13.1) years. Tear enlargement occurred in 138 (60%) shoulders. Full-thickness tears were at greater risk for enlargement compared with partial-thickness (hazard ratio [HR] 2.93, 95% confidence interval [CI] 1.71-5.03, P < .0001) and control shoulders (HR 18.8, 95% CI 4.63-76.1, P < .0001). Mean survival rates from Kaplan-Meier analyses indicate that full-thickness tears enlarged earlier (mean 4.7, 95% CI 4.1-5.2 years) than partial-thickness (mean 7.4, 95% CI 6.2-8.5 years) and control shoulders (mean 9.7, 95% CI 9.0-10.4 years). Tear presence in the dominant shoulder was associated with a greater enlargement risk (HR 1.70, 95% CI 1.21-1.39, P = .002). Patient age (P = .37) and gender (P = .74) were not associated with tear enlargement. The 2-, 5-, and 8-year survivorship free of tear enlargement for full-thickness tears was 74%, 42%, and 20%, respectively. Shoulder pain developed in 131 (57%) shoulders. Pain development was associated with tear enlargement (HR 1.79, 95% CI 1.24-2.58, P = .002) and was more common in full-thickness tears compared with controls (P = .0003) and partial tears (P = .01). An analysis of progression of muscle degeneration was performed in 138 shoulders with full-thickness tears. Tear enlargement was seen in 104 of 138 (75%) of these shoulders during follow-up (median 7.7 [interquartile range 6.0] years). Progression of muscle fatty degeneration was seen in the supraspinatus in 46 (33%) and the infraspinatus in 40 (29%) shoulders. Adjusting for age, both the presence of fatty muscle degeneration and the progression of muscle changes for both the supraspinatus (P < .0001) and infraspinatus (P < .0001) muscles were associated with tear size. For both the supraspinatus (P = .03) and infraspinatus (P = .03) muscles, tear enlargement was significantly associated with progression of muscle fatty degeneration. Anterior cable integrity was significantly associated with the risk of muscle degeneration progression for both the supraspinatus (P < .0001) and the infraspinatus (P = .005) muscles. CONCLUSIONS: Asymptomatic degenerative rotator cuff tears progress in patient 65 years and younger. Full-thickness rotator cuff tears have a higher risk of continued tear enlargement, progression of fatty muscle degeneration, and pain development than partial-thickness tears.


Assuntos
Lacerações , Lesões do Manguito Rotador , Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Lesões do Manguito Rotador/complicações , Lesões do Manguito Rotador/diagnóstico por imagem , Seguimentos , Estudos Longitudinais , Estudos Prospectivos , Ruptura , Atrofia Muscular , Dor de Ombro/etiologia
4.
JSES Int ; 7(2): 277-284, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36911784

RESUMO

Background: Reverse total shoulder arthroplasty (RTSA) has been well-described as a surgical solution to manage rotator cuff tear arthropathy in elderly, low demand paitents. As experience has increased along with improvements in technique and implant design, RTSA has become increasingly used to manage more varied pathologic conditions of the shoulder in younger, more active patients. This study evaluates outcomes in a consecutive series of patients aged 60 years old and younger after undergoing RTSA. Methods: There were 94 shoulders in 89 patients enrolled. Mean age of the cohort was 54.8 (range 18-60 years). Surgical indications included rotator cuff tear arthropathy, irreparable rotator cuff tear without arthritis, glenohumeral arthritis with erosive glenoid deformity, inflammatory arthropathy, proximal humerus fracture nonunion/malunion and failed prior shoulder arthroplasty. Sixty-one shoulders (70%) had undergone at least one prior surgery. Of these, 6 shoulders (6% of total cohort) had a prior failed arthroplasty. Clinical outcomes (American Shoulder and Elbow Surgeons score, Western Ontario Osteoarthritis of the Shoulder index; visual analog scale pain), radiographic outcomes and complications were analyzed and assessed for correlation with patient demographic factors. Results: The mean follow-up for this cohort was 4.9 years (range 2-12 years). Subjects experienced improvements in ASES score and pain (P < .001) and active forward elevation (88° preop to 135° postop, P < .001). Prior operation correlated with worse postoperative ASES and WOOS scores. Higher demand occupation correlated with less improvement in pain scores. The overall complication rate was 12%. Seven shoulders (7%) underwent an additional procedure. There was a 2% incidence of dislocation and a 4% incidence of acromial stress fracture. There was a 36% incidence of notching. Conclusion: With medium-term follow-up, RTSA is a reliable and predictable operation to manage various pathologic conditions in patients aged 60 years or less. Patients predictably experience significant improvements in pain and range of motion while assuming a modest complication risk. Long-term study is needed to understand potential for late complications or implant failure.

5.
J Shoulder Elbow Surg ; 32(4): 760-770, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36690173

RESUMO

OBJECTIVE: To compare range of motion (ROM) and patient-reported outcomes (PROs) between a structured home exercise program (HEP) and active, supervised physiotherapy (PT) after primary Reverse total shoulder arthroplasty (RTSA) by performing a multicenter randomized clinical trial. METHODS: Patients undergoing primary RTSA at 2 centers were randomized to either a HEP group, in which they were given a handout and a rope pulley, or a PT group, in which they were given a standardized prescription. Surgical technique and implants were standardized. At baseline, 6 weeks, 3 months, and 1 year postoperatively, we obtained American Shoulder and Elbow Surgeons scores, Western Ontario Osteoarthritis Scores, visual analogue scale for pain scores, and measured ROM via videotape. On video, ROM was then measured by blinded observers. At all study visits, patients were asked how many days per week they were in PT and how many days a week they completed HEP to determine compliance and crossover. An a priori power analysis suggested 29 patients per group, 56 patients total to detect a difference of 30° in active forward elevation with a power of 0.8 at a 2-sided alpha of 0.05. RESULTS: 89 patients were randomized, 43 to PT, and 46 to HEP. We obtained 1-year PRO follow-up on 83 patients (93%) and ROM follow-up on 73 patients (82%). Nine patients (20%) crossed over from HEP to PT and 2 patients (4%) crossed over from PT to HEP. Complications occurred in 13% of HEP and 17% of PT patients (P = .629). Using mixed models that account for baseline values, there were no significant differences between groups in PROs or ROM at final follow-up. CONCLUSION: In this 2-center, randomized clinical trial, there were no significant differences in patient outcomes or ROM between HEP and PT after RTSA. These findings suggest that it may not be necessary to recommend PT as a protocol for all patients after RTSA.


Assuntos
Artroplastia do Ombro , Articulação do Ombro , Humanos , Artroplastia do Ombro/métodos , Articulação do Ombro/cirurgia , Resultado do Tratamento , Modalidades de Fisioterapia , Ontário , Amplitude de Movimento Articular , Estudos Retrospectivos
6.
J Shoulder Elbow Surg ; 29(3): 451-458, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32067709

RESUMO

BACKGROUND: The prevalence of subscapularis and long head of biceps (LHB) in relation to the presence and severity of posterosuperior (PS) rotator cuff disease is not known. METHODS: Subjects with asymptomatic rotator cuff tears were enrolled for this prospective longitudinal study (n = 354) and followed annually with shoulder ultrasonography and clinical evaluations to assess for the presence of subscapularis, LHB, and PS rotator cuff pathology and pain development. RESULTS: Subscapularis pathology developed in 14% of shoulders over a median follow-up of 5 years, with partial-thickness tearing occurring most commonly (83%). Age, sex, and hand dominance were not associated with subscapularis pathology. A greater proportion of concomitant full-thickness PS cuff tears were observed in shoulders that developed subscapularis tears (76% vs. 50%, P = .002). The PS cuff tear width (10 mm vs. 14 mm, P = .01) at the time of enrollment and both tear width (10 mm vs. 15 mm, P = .003) and length (12 mm vs. 15.5 mm, P = .02) at the time of diagnosis of subscapularis pathology were greater in subscapularis-torn shoulders. LHB pathology was prevalent in 34% of shoulders, with dislocation/subluxation occurring in 63% and higher prevalence in subscapularis-torn shoulders (71% vs. 12%, P < .01). Subscapularis-torn shoulders were more likely to develop pain (67% vs. 45%, P = .004), and concomitant PS cuff tear enlargement was associated with greater risk for pain development (76% vs. 36%, P = .01). CONCLUSIONS: The development of subscapularis and LHB pathology is significantly related to the size of the PS cuff tear. Subscapularis involvement is associated with greater risk of pain development in degenerative rotator cuff disease.


Assuntos
Lesões do Manguito Rotador/complicações , Lesões do Manguito Rotador/diagnóstico por imagem , Traumatismos dos Tendões/diagnóstico por imagem , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Luxação do Ombro/etiologia , Dor de Ombro/etiologia , Ultrassonografia
7.
Soc Sci Med ; 156: 55-63, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27017091

RESUMO

RATIONALE: Low social support has been linked to negative health outcomes in breast cancer patients. OBJECTIVE: We examined associations between perceived social support, neighborhood socioeconomic deprivation, and neighborhood-level social support in early-stage breast cancer patients and controls. METHODS: This two-year longitudinal study in the United States included information collected from telephone interviews and clinical records of 541 early-stage patients and 542 controls recruited from 2003 to 2007. Social support was assessed using the Medical Outcomes Study Social Support Survey (MOS-SS). Residential addresses were geocoded and used to develop measures including neighborhood social support (based on MOS-SS scores from nearby controls) and neighborhood socioeconomic deprivation (a composite index of census tract characteristics). Latent trajectory models were used to determine effects of neighborhood conditions on the stable (intercept) and changing (slope) aspects of social support. RESULTS: In a model with only neighborhood variables, greater socioeconomic deprivation was associated with patients' lower stable social support (standardized estimate = -0.12, p = 0.027); neighborhood-level social support was associated with social support change (standardized estimate = 0.17, p = 0.046). After adding individual-level covariates, there were no direct neighborhood effects on social support. In patients, neighborhood socioeconomic deprivation was associated with support indirectly through marriage, insurance status, negative affect, and general health. In controls, neighborhood socioeconomic deprivation was associated with support indirectly through marriage (p < 0.05). CONCLUSION: Indirect effects of neighborhood socioeconomic deprivation on social support differed in patients and controls. Psychosocial and neighborhood interventions may help patients with low social support, particularly patients without partnered relationships in deprived areas.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Características de Residência/estatística & dados numéricos , Apoio Social , Adulto , Idoso , Neoplasias da Mama/mortalidade , Estudos de Casos e Controles , Feminino , Disparidades nos Níveis de Saúde , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores Socioeconômicos , Estados Unidos/epidemiologia
8.
J Cancer Surviv ; 8(1): 21-30, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24030573

RESUMO

PURPOSE: There has been a paucity of interventions developed for African American women to address persistent health disparities between African American and Caucasian breast cancer patients. We developed and piloted a technologically innovative, culturally targeted, cancer-communication intervention for African American breast cancer patients using African American breast cancer survivor stories. METHODS: We rated 917 clips from a video library of survivors' stories for likability, clarity and length, and emotional impact (scaled responses) and categorized each clip by theme (Coping, Support and Relationships, Healthcare Experiences, Follow-up Care, Quality of Life, and Treatment Side Effects). We selected 207 clips told by 35 survivors (32-68 years old; 4-30 years after diagnosis), fitting one of 12 story topics, for inclusion in the interactive video program loaded onto a touch-screen computer. Videos can be searched by storyteller or story topics; stories with the strongest emotional impact were displayed first in the video program. RESULTS: We pilot tested the video program with ten African American breast cancer survivors (mean age, 54; range 39-68 years), who, after training, watched videos and then evaluated the stories and video-program usability. Survivor stories were found to be "interesting and informative," and usability was rated highly. Participants identified with storytellers (e.g., they "think a lot like me," "have values like mine") and agreed that the stories convinced them to receive recommended surveillance mammograms. CONCLUSIONS: This novel, cancer-communication technology using survivor stories was very favorably evaluated by breast cancer survivors and is now being tested in a randomized controlled clinical trial. IMPLICATIONS FOR CANCER SURVIVORS: Breast cancer survivors can draw support and information from a variety of sources, including from other breast cancer survivors. We developed the survivor stories video program specifically for African American survivors to help improve their quality of life and adherence to follow-up care. Breast cancer survivors' experiences with treatment and living with cancer make them especially credible messengers of cancer information. Our novel, interactive technology is being tested in a randomized controlled trial and will be more broadly disseminated to reach a wider audience.


Assuntos
Negro ou Afro-Americano/psicologia , Promoção da Saúde/métodos , Disparidades em Assistência à Saúde , Narração , Neoplasias/psicologia , Educação de Pacientes como Assunto/métodos , Sobreviventes/psicologia , Adulto , Idoso , Atitude Frente a Saúde , Diagnóstico Precoce , Emoções , Feminino , Humanos , Mamografia/psicologia , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Cooperação do Paciente , Projetos Piloto , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Fatores Socioeconômicos , Gravação em Vídeo
9.
Breast Cancer Res Treat ; 129(3): 877-86, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21519836

RESUMO

Greater chronic disease burden may decrease quality of life (QOL) of breast cancer survivors. Our objective was to investigate the association between chronic disease burden and QOL in breast cancer survivors at 1 year post-diagnosis. We analyzed cross-sectional data collected 1 year post-diagnosis from a sample of female breast cancer survivors identified from the Missouri cancer registry. We used eight RAND-36 subscales to assess physical, emotional, and social functioning QOL domains. Using Katz's measure of comorbidity, we computed chronic disease burden (0, 1, and 2+). Multivariable general linear models for each QOL subscale were used to examine associations between chronic disease burden and QOL after controlling for potential covariates: socio-demographic, clinical, psychosocial, behavioral risk factors, and access to medical care. Participants (n = 1089) were 58-year old on average (range 27-96) and mostly White (92%), married (68%), had at least a high school education (95%), and had health insurance (97%). Sixty-six percent of survivors had a chronic disease burden score of 0, 17% had 1, and 17% had 2+. Chronic disease burden was significantly associated with each QOL subscale in crude models (P < 0.001). In fully adjusted models, chronic disease burden was still significantly correlated with six subscales, but not with the emotional well-being and role limitations due to emotional problems subscales. One year post-diagnosis, breast cancer survivors with higher chronic disease burden had lower physical and social functioning than survivors without additional health conditions. These differences were not fully explained by relevant covariates. Identifying modifiable targets for intervention will be critical for improving QOL outcomes among survivors who have other chronic health conditions.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/psicologia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Comorbidade , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Missouri , Classe Social , Sobreviventes/estatística & dados numéricos , População Branca
10.
Ann Surg Oncol ; 15(10): 2709-19, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18483831

RESUMO

BACKGROUND: Ductal carcinoma in situ (DCIS) represents 20-30% of mammographically detected breast cancers, but the role of lymph node assessment (LNA) in women with DCIS remains unclear. METHODS: Using the 1988-2002 Surveillance, Epidemiology, and End Results (SEER) Program data, we conducted a case-control study to identify variables associated with (1) LNA in DCIS patients and (2) use of axillary lymph node dissection (ALND) compared with sentinel lymph node biopsy (SLNB). Using separate multivariable logistic regression models, we identified patient and tumor-related factors associated with LNA (1988-2002) and with the method used (recorded only in 1998-2002). We report adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Of 23,502 women with DCIS, 37% underwent mastectomy and 63% underwent breast-conservation therapy (BCT); 6,650 cases (28%) underwent LNA. Women younger than 80 years (aOR 1.47; 95% CI 1.24-1.75) or who had mastectomy (aOR 11.06; 95% CI 10.30-11.90), tumor size greater than 9 mm (aORs ranged from 1.27-1.97 for 10-mm increments from 10 to 50 mm or more) or poorly differentiated grade (aOR 1.33; 95% CI 1.11-1.55) were more likely to have had a LNA. From 1998 to 2002, 10,637 women underwent resection for DCIS (21% mastectomy; 79% BCT); of these, 2,219 (21%) had LNA (73% mastectomy; 27% BCT). Mastectomy patients were 3.52 times more likely to receive ALND (95% CI 2.71-4.57) than SLNB, after controlling for other factors. CONCLUSION: Optimal guidelines for use of LNA in DCIS have not been defined. However, there appeared to be a persistent and excessive utilization of ALND for LNA in women with DCIS (1998-2002).


Assuntos
Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/secundário , Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Estudos de Casos e Controles , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Mastectomia , Invasividade Neoplásica , Razão de Chances , Prognóstico , Programa de SEER , Biópsia de Linfonodo Sentinela , Fatores de Tempo
11.
Mol Microbiol ; 63(5): 1385-98, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17244196

RESUMO

Yeast cell walls are critical for maintaining cell integrity, particularly in the face of challenges such as growth in mammalian hosts. The pathogenic fungus Cryptococcus neoformans additionally anchors its polysaccharide capsule to the cell surface via alpha(1-3) glucan in the wall. Cryptococcal cells disrupted in their alpha glucan synthase gene were sensitive to stresses, including temperature, and showed difficulty dividing. These cells lacked surface capsule, although they continued to shed capsule material into the environment. Electron microscopy showed that the alpha glucan that is usually localized to the outer portion of the cell wall was absent, the outer region of the wall was highly disorganized, and the inner region was hypertrophic. Analysis of cell wall composition demonstrated complete loss of alpha glucan accompanied by a compensatory increase in chitin/chitosan and a redistribution of beta glucan between cell wall fractions. The mutants were unable to grow ina mouse model of infection, but caused death in nematodes. These studies integrate morphological and biochemical investigations of the role of alpha glucan in the cryptococcal cell wall.


Assuntos
Parede Celular/química , Cryptococcus neoformans/patogenicidade , Cryptococcus neoformans/ultraestrutura , Glucanos/fisiologia , Animais , Caenorhabditis elegans/microbiologia , Parede Celular/genética , Parede Celular/ultraestrutura , Quitina/análise , Quitosana/análise , Cryptococcus neoformans/genética , Cryptococcus neoformans/crescimento & desenvolvimento , Modelos Animais de Doenças , Deleção de Genes , Glucosiltransferases/genética , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Mutagênese Insercional , Virulência/genética , beta-Glucanas/análise
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