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1.
Skeletal Radiol ; 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38499893

ABSTRACT

Chronic recurrent multifocal osteomyelitis (CRMO), an autoinflammatory bone disorder characterized by non-bacterial osteomyelitis causing recurrent multifocal bone lesions, is a well-known, yet uncommon pediatric condition that rarely affects adults; to date, it has never been diagnosed over the age of 75. The following report will discuss the first octogenarian diagnosed with CRMO and therefore represents an exceptionally rare presentation of a rare disease. An 83-year-old woman presented with progressive right shoulder, forearm, and hip pain, with associated weight loss and global weakness, requiring a wheelchair for mobility. Imaging revealed a pathologic right ulna fracture in addition to lytic lesions of the right proximal humerus and proximal femur. The clinical picture was thus that of a patient with probable multiple myeloma versus metastatic disease. After an extensive workup, however, the lesions were not malignant; histologic findings were instead suggestive of chronic osteomyelitis with negative cultures. Given the multifocal nature of this condition, combined with a lack of clinical symptoms of infection, a diagnosis of CRMO was rendered. The patient underwent intramedullary nailing of the right femur and splinting of the ulna, with a subsequent remarkable recovery to painless ambulation, complete union of the right ulna fracture, and resolution of the lytic lesions without receiving any targeted medical treatment. This case highlights the importance of maintaining CRMO on the differential for multifocal skeletal lesions, regardless of age. Performing a thorough workup with necessary imaging, biopsy, and culture are critical to establishing this diagnosis, which can only made as a diagnosis of exclusion.

2.
J Orthop Case Rep ; 14(2): 59-64, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38420244

ABSTRACT

Introduction: This case report describes the third documented example of primary esophageal carcinoma metastasizing to the patella and the first documented example of esophageal carcinoma metastasizing to synovium. Case Report: A 67-year-old man with a history of metastatic esophageal carcinoma presents with right knee pain and an aggressive, destructive lesion involving the superior patella. Biopsy revealed esophageal carcinoma. After ineffective radiation, he underwent resection of the tumor-filled bone and quadricep advancement. Two months later, a recurrent tumor involving the entire patella and significant knee synovitis was observed. He underwent a total patellectomy with a radical anterior synovectomy. Further assessment showed that the entire synovium was replaced with metastatic carcinoma. Conclusion: This report describes an atypical presentation of metastasis with patella and synovium involvement.

3.
J Family Med Prim Care ; 12(9): 1979-1983, 2023 Sep.
Article in English | MEDLINE | ID: mdl-38024888

ABSTRACT

Introduction: The management of benign bone lesions is controversial as it is dependent on a multitude of factors such as age, anatomic location, comorbidities, lesion metabolic activity, surgeon preferences, and goals of care, among others. Thus far, many studies have attempted to report on these lesions; however, most are heterogeneous compilations of benign and malignant lesions with nearly all failing to report patient treatment and none of which have originated from a suburban area of the United States. The goal of this study was to establish a modern database dedicated solely to benign bone tumors to reflect current diagnosis and treatment trends in suburban New York. Materials and Methods: This was a multicenter retrospective observational study with inclusion criteria limited to benign bone lesions of all ages. Malignant lesions were excluded. Patients were drawn from both primary care provider and surgeon records, with documentation of their associated management. Results: A total of 689 patients met inclusion criteria. The overall operative rate for this cohort was 71.6%. In agreement with current literature, aneurysmal bone cysts, giant cell tumors, and osteochondromas underwent surgery more frequently than enchondromas; older patients underwent surgery less frequently; benign bone lesions were more commonly found in younger males, and the distal femur and proximal tibia were the most common locations for lesions (P < .05 for all findings). Conclusion: This study demonstrates the management of a globally representative variety of benign bone lesions in a diverse suburban population of New York and should facilitate future research on how lesion type, location, management, and other factors relate to patient outcomes.

4.
Gynecol Oncol ; 172: 82-91, 2023 05.
Article in English | MEDLINE | ID: mdl-37001446

ABSTRACT

PURPOSE: Dickkopf-1 (DKK1) is a Wnt signaling modulator promoting tumor growth, metastasis, angiogenesis, and immunosuppression by regulating innate immunity. DKK1 is over-expressed in gynecologic cancers and is associated with shortened survival. DKN-01 is a humanized monoclonal antibody with DKK1 neutralizing activity that may provide clinical benefit to patients whose tumors have overexpression of DKK1 or Wnt genetic alterations. METHODS: We conducted an open-label, Phase 2 basket study with 2-stage design in patients with endometrial carcinoma (EC) and platinum-resistant/refractory epithelial ovarian cancer. DKN-01 was administered either as monotherapy or in combination with weekly paclitaxel at investigator's discretion. All patients underwent NGS testing prior to enrollment; tumor tissue was also tested for DKK1 expression by RNAscope pre-treatment and after cycle 1 if available. At least 50% of patients were required to have a Wnt signaling alteration either directly or tangentially. This publication reports results from the EC population overall and by DKK1-expression. RESULTS: DKN-01 monotherapy and in combination with paclitaxel was more effective in patients with high DKK1-expressing tumors compared to low-expressing tumors. DKN-01 monotherapy demonstrated an objective response rate [ORR] of 25.0% vs. 0%; disease control rate [DCR] of 62.5% vs. 6.7%; median progression-free survival [PFS] was 4.3 vs. 1.8 months, and overall survival [OS] was 11.0 vs. 8.2 months in DKK1-high vs DKK1-low patients. Similarly, DKN-01 in combination with paclitaxel demonstrated greater clinical activity in patients with DKK1-high tumors compared to DKK1-low tumors: DCR was 55% vs. 44%; median PFS was 5.4 vs. 1.8 months; and OS was 19.1 vs. 10.1 months. Wnt activating mutations correlated with higher DKK1 expression. DKN-01 was well tolerated as a monotherapy and in combination with paclitaxel. CONCLUSIONS: Collectively, data demonstrates promising clinical activity of a well-tolerated drug, DKN-01, in EC patients with high tumoral DKK1 expression which frequently corresponded to the presence of a Wnt activating mutation. Future development will focus on using DKN-01 in DKK1-high EC patients in combination with immunotherapy.


Subject(s)
Antineoplastic Agents , Endometrial Neoplasms , Ovarian Neoplasms , Female , Humans , Antineoplastic Agents/therapeutic use , Paclitaxel , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/etiology , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/genetics , Antibodies, Monoclonal/therapeutic use , Biomarkers , Ovarian Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Intercellular Signaling Peptides and Proteins/genetics
5.
J Hand Surg Glob Online ; 4(4): 233-238, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35880153

ABSTRACT

In this case report, we describe a novel occurrence of tumoral calcium pyrophosphate dihydrate crystal deposition disease (TCPPDCD) in a 76-year-old man that presented as an unusual, intraosseous, metadiaphyseal lesion of a long bone causing a pathologic fracture. A routine intralesional biopsy was performed, demonstrating granular deposits composed of polarizing, overlapping rhomboid crystals consistent with TCPPDCD. With limited numbers of reported cases of TCPPDCD, and the atypical intraosseous origin seen in this case, it is paramount to thoroughly evaluate all cases of TCPPDCD to clearly differentiate key findings that are essential in diagnosing and managing TCPPDCD.

7.
Bone Jt Open ; 2(4): 236-242, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33870729

ABSTRACT

AIMS: The aim of this study was to assess orthopaedic oncologic patient morbidity resulting from COVID-19 related institutional delays and surgical shutdowns during the first wave of the pandemic in New York, USA. METHODS: A single-centre retrospective observational study was conducted of all orthopaedic oncologic patients undergoing surgical evaluation from March to June 2020. Patients were prioritized as level 0-IV, 0 being elective and IV being emergent. Only priority levels 0 to III were included. Delay duration was measured in days and resulting morbidities were categorized into seven groups: prolonged pain/disability; unplanned preoperative radiation and/or chemotherapy; local tumour progression; increased systemic disease; missed opportunity for surgery due to progression of disease/lost to follow up; delay in diagnosis; and no morbidity. RESULTS: Overall, 25 patients met inclusion criteria. There were eight benign tumours, seven metastatic, seven primary sarcomas, one multiple myeloma, and two patients without a biopsy proven diagnosis. There was no priority level 0, two priority level I, six priority level II, and 17 priority level III cases. The mean duration of delay for priority level I was 114 days (84 to 143), priority level II was 88 days (63 to 133), and priority level III was 77 days (35 to 269). Prolonged pain/disability and delay in diagnosis, affecting 52% and 40%,respectively, represented the two most frequent morbidities. Local tumour progression and increased systemic disease affected 32% and 24% respectively. No patients tested positive for COVID-19. CONCLUSION: COVID-19 related delays in surgical management led to major morbidity in this studied orthopaedic oncologic patient population. By understanding these morbidities through clearer hindsight, a thoughtful approach can be developed to balance the risk of COVID-19 exposure versus delay in treatment, ensuring optimal care for orthopedic oncologic patients as the pandemic continues with intermittent calls for halting surgery. Cite this article: Bone Jt Open 2021;2(4):236-242.

8.
J Orthop ; 22: 198-202, 2020.
Article in English | MEDLINE | ID: mdl-32425417

ABSTRACT

BACKGROUND AND OBJECTIVES: Cemented hip arthroplasty is considered the standard of care for treating both osteoporotic femoral neck fractures and pathologic disease of the proximal femur due to the ability to achieve strong fixation in poor quality bone. There is minimal literature evaluating uncemented arthroplasty for pathologic disease of the proximal femur. This objective of this study is to compare outcomes of patients undergoing cemented and uncemented arthroplasty of the proximal femur for an oncologic indication. METHODS: Patients who underwent hip arthroplasty procedures in one health system for an oncologic indication were identified. Demographics, cancer history, operative history, and complications were collected retrospectively. Harris Hip Scores (HHS) and Musculoskeletal Tumor Society Scores (MSTS) were prospectively collected via telephone. RESULTS: 41 patients met criteria for review. 18 underwent cemented and 23 underwent uncemented arthroplasty. There were no significant differences in age, demographics, complications, 30-day mortality, intraoperative blood loss, transfusion requirements, average HHS, or average MSTS. CONCLUSION: No significant differences were found for patients undergoing hip arthroplasty for an oncologic indication regardless of whether or not the femoral component was cemented. Our results suggest that cemented and uncemented techniques are both safe and effective methods to be used at the oncologic surgeon's discretion.

9.
Clin Cancer Res ; 26(15): 3958-3968, 2020 08 01.
Article in English | MEDLINE | ID: mdl-32299817

ABSTRACT

PURPOSE: A persistent issue in cancer drug development is the discordance between robust antitumor drug activity observed in laboratory models and the limited benefit frequently observed when patients are treated with the same agents in clinical trials. Difficulties in accurately modeling the complexities of human tumors may underlie this problem. To address this issue, we developed Comparative In Vivo Oncology (CIVO), which enables in situ investigation of multiple microdosed drugs simultaneously in a patient's tumor. This study was designed to test CIVO's safety and feasibility in patients with soft tissue sarcoma (STS). PATIENTS AND METHODS: We conducted a single arm, prospective, 13-patient pilot study. Patients scheduled for incisional biopsy or tumor resection were CIVO-injected 1 to 3 days prior to surgery. Saline or microdoses of anticancer agents were percutaneously injected into the tumor in a columnar fashion through each of eight needles. Following excision, drug responses were evaluated in the injected tissue. RESULTS: The primary objective was met, establishing CIVO's feasibility and safety. Device-related adverse events were limited to transient grade 1 nonserious events. In addition, biomarker evaluation of localized tumor response to CIVO microinjected drugs by IHC or with NanoString GeoMx Digital Spatial Profiler demonstrated consistency with known mechanisms of action of each drug, impact on the tumor microenvironment, and historic clinical activity. CONCLUSIONS: These results are an advance toward use of CIVO as a translational research tool for early evaluation of investigational agents and drug combinations in a novel approach to phase 0 trials.See related commentary by Sleijfer and Lolkema, p. 3897.


Subject(s)
Antineoplastic Agents , Sarcoma , Antineoplastic Agents/adverse effects , Humans , Pilot Projects , Prospective Studies , Sarcoma/drug therapy , Tumor Microenvironment
10.
J Orthop Surg Res ; 15(1): 94, 2020 Mar 05.
Article in English | MEDLINE | ID: mdl-32138774

ABSTRACT

BACKGROUND: 5-Aminolevulinic acid (5-ALA), a fluorescent contrast agent, has been used for tumor paint and photodynamic therapy (PDT) for various tumors, but its use with soft tissue sarcomas is not well documented. Myxofibrosarcoma, a subtype of soft tissue sarcoma with a high local recurrence rate, may benefit from similar types of treatment. The purpose of this study was to analyze the effects of 5-ALA tumor paint and PDT on a myxofibrosarcoma cell line. METHODS: Tumor paint was assessed by exposing micromass pellets of human adipose-derived stromal (ADS) cells or myxofibrosarcoma (MUG-Myx1) cells to 5-ALA. Cell pellets were then visualized using a microscope at established excitation and emission wavelengths. Corrected total cell fluorescence was calculated per accepted protocols. Photodynamic therapy was similarly assessed by exposing ADS and MUG-Myx1 cells to 5-ALA, with subsequent analysis via flow cytometry and real-time confocal microscopy. RESULTS: The use of 5-ALA tumor paint led to a selective fluorescence in MUG-Myx1 cells. Findings were confirmed by flow cytometry. Interestingly, flow cytometry results showed progressive selective cell death with increasing 5-ALA exposure as a result of the PDT effect. PDT was further confirmed using confocal microscopy, which revealed progressive cellular bubble formation consistent with advancing stages of cell death-a finding that was not seen in control ADS cells. CONCLUSIONS: 5-ALA tumor paint and PDT were successfully used on a human myxofibrosarcoma cell line (MUG-Myx1). Results from this study showed both selective fluorescent tagging and selective cytotoxicity of 5-ALA toward malignant myxofibrosarcoma cells, while sparing benign adipose control cells. This finding was further confirmed in a dramatic time-lapse video, visually confirming active, targeted cell death. 5-ALA's two-pronged application of selective tumor identification and cytotoxicity may transform surgical and medical approaches for treating soft tissue sarcomas.


Subject(s)
Aminolevulinic Acid/toxicity , Contrast Media/toxicity , Fibroma/therapy , Fibrosarcoma/therapy , Photochemotherapy/methods , Aminolevulinic Acid/analysis , Aminolevulinic Acid/therapeutic use , Cell Line, Tumor , Contrast Media/analysis , Contrast Media/therapeutic use , Fibroma/diagnosis , Fibrosarcoma/diagnosis , Humans , Microscopy, Confocal/methods
11.
J Arthroplasty ; 35(6): 1480-1483, 2020 06.
Article in English | MEDLINE | ID: mdl-32029349

ABSTRACT

BACKGROUND: The Comprehensive Care for Joint Replacement model aims to support more efficient care for patients. We examined the impact of patient and surgical characteristics, post-acute care, and clinical outcomes on episode of care (EOC) costs in patients undergoing hip arthroplasty for all diagnoses. METHODS: We retrospectively collected data from a large database of patients undergoing hip arthroplasty for oncologic and nononcologic diagnoses between 2014 and 2017. We compared EOC costs and outcomes between the 2 groups using Student's t-tests. We estimated the association between an oncologic-associated procedure and EOC costs from a multiple regression analysis. RESULTS: There were 2122 total patients included: 1993 in the nononcologic group and 129 in the oncologic group. The length of stay was significantly greater in the oncologic group (7.2 vs 4.2 days, P = .00). In the post-acute period, a greater proportion of oncologic patients was readmitted (29% vs 14%, P = .05) and discharged to skilled nursing (93% vs 51%, P = .00). Index hospitalization costs (mean difference [MD] $1561, P = .05), skilled nursing costs (MD $5932, P = .001), and total EOC costs (MD $20,012, P = .00) were all greater in the oncologic group. Along with increasing age and fracture diagnosis, an oncologic diagnosis is independently associated with greater EOC costs from a multivariate analysis (ß = 16,163 ± 2258, P = .00, r2 = 29%). CONCLUSION: Comprehensive Care for Joint Replacement should incorporate risk adjustment for oncologic disease because hip arthroplasty for an oncologic diagnosis is associated with worse outcomes and greater costs than in the general population.


Subject(s)
Arthroplasty, Replacement, Hip , Episode of Care , Humans , Length of Stay , Medicare , Patient Discharge , Retrospective Studies , United States
12.
Proc Natl Acad Sci U S A ; 117(9): 5049-5058, 2020 03 03.
Article in English | MEDLINE | ID: mdl-32051250

ABSTRACT

The coordinated redistribution of sugars from mature "source" leaves to developing "sink" leaves requires tight regulation of sugar transport between cells via plasmodesmata (PD). Although fundamental to plant physiology, the mechanisms that control PD transport and thereby support development of new leaves have remained elusive. From a forward genetic screen for altered PD transport, we discovered that the conserved eukaryotic glucose-TOR (TARGET OF RAPAMYCIN) metabolic signaling network restricts PD transport in leaves. Genetic approaches and chemical or physiological treatments to either promote or disrupt TOR activity demonstrate that glucose-activated TOR decreases PD transport in leaves. We further found that TOR is significantly more active in mature leaves photosynthesizing excess sugars than in young, growing leaves, and that this increase in TOR activity correlates with decreased rates of PD transport. We conclude that leaf cells regulate PD trafficking in response to changing carbohydrate availability monitored by the TOR pathway.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Plant Cells/metabolism , Plant Leaves/metabolism , Plasmodesmata/metabolism , Arabidopsis/embryology , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Biological Transport , Carbohydrate Metabolism , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Expression Regulation, Plant , Gene Knockdown Techniques , Gene Silencing , Plant Leaves/growth & development , Protein Transport , Signal Transduction , Nicotiana/genetics , Nicotiana/metabolism
13.
Curr Urol ; 9(4): 202-208, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28413381

ABSTRACT

We present a 55-year-old male, with good performance status who was diagnosed with a case of metastatic renal cell carcinoma following a pathologic femur fracture. Despite good performance status, multifocal metastases and poor-prognostic features portended a grim prognosis with predicted overall survival of less than nine months. On initial presentation, he was excluded from cytoreductive nephrectomy based on brain metastasis and interleukin-2 was not pursued as the primary tumor was to be left in situ. The patient was reconsidered for cytoreductive nephrectomy after sustained response to fifth line targeted therapies with shrinkage of tumor burden. The post-operative course was uneventful and the patient was discharged home on postoperative day one. Temsirolimus was resumed one week after surgery and the patient reported returning to his normal activities at the two week follow-up visit. We highlight important clinical features of metastatic renal cell carcinoma, the surgical considerations for cytoreductive nephrectomy and the detailed multidisciplinary care the patient received throughout this case report.

14.
Gynecol Oncol ; 143(3): 504-510, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27678295

ABSTRACT

OBJECTIVES: The majority of women with Stage III/IV ovarian cancer who achieve clinical complete response with frontline standard of care will relapse within 2years. Vigil immunotherapy, a GMCSF/bi-shRNA furin DNA engineered autologous tumor cell (EATC) product, demonstrated safety and induction of circulating activated T-cells against autologous tumor in Phase I trial Senzer et al. (2012, 2013) . Our objectives for this study include evaluation of safety, immune response and recurrence free survival (RFS). METHODS: This is a Phase II crossover trial of Vigil (1.0×107 cells/intradermal injection/month for 4 to 12 doses) in Stage III/IV ovarian cancer patients achieving cCR (normal imaging, CA-125≤35units/ml, physical exam, and no symptoms suggestive of the presence of active disease) following primary surgical debulking and carboplatin/paclitaxel adjuvant or neoadjuvant chemotherapy. Patients received Vigil or standard of care during the maintenance period. RESULTS: Forty-two patients were entered into trial, 31 received Vigil and 11 received standard of care. No≥Grade 3 toxicity related to product was observed. A marked induction of circulating activated T-cell population was observed against individual, pre-processed autologous tumor in the Vigil arm as compared to pre-Vigil baseline using IFNγ ELISPOT response (30/31 negative ELISPOT pre Vigil to 31/31 positive ELISPOT post Vigil, median 134 spots). Moreover, in correlation with ELISPOT response, RFS from time of procurement was improved (mean 826days/median 604days in the Vigil arm from mean 481days/median 377days in the control arm, p=0.033). CONCLUSION: In conjunction with the demonstrated safety, the high rate of induction of T-cell activation and correlation with improvement in RFS justify further Phase II/III assessment of Vigil.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cancer Vaccines/therapeutic use , Carcinoma, Endometrioid/drug therapy , Cytoreduction Surgical Procedures , Neoplasms, Cystic, Mucinous, and Serous/drug therapy , Ovarian Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carboplatin/administration & dosage , Carcinoma, Endometrioid/pathology , Cross-Over Studies , Disease-Free Survival , Female , Humans , Middle Aged , Neoadjuvant Therapy , Neoplasms, Cystic, Mucinous, and Serous/pathology , Ovarian Neoplasms/pathology , Paclitaxel/administration & dosage , T-Lymphocytes
15.
JBJS Case Connect ; 6(4): e86, 2016.
Article in English | MEDLINE | ID: mdl-29252740

ABSTRACT

CASE: A 55-year-old man presented with a history of forefoot pain and swelling. Radiographs revealed a mass with internal calcifications and osseous erosion of the fifth metatarsophalangeal bone. The mass was isointense to muscle on T1-weighted magnetic resonance imaging (MRI) and hyperintense on T2-weighted MRI. A biopsy was performed, and intraoperatively, the lesion appeared as chalky white material, which under polarized light microscopy was composed of weakly positively birefringent rhomboid crystals, leading to a diagnosis of tophaceous pseudogout. CONCLUSION: Tophaceus pseudogout should be included in the differential diagnosis of neoplastic-appearing lesions in the foot, and polarized light microscopy should be used when examining biopsy specimens.


Subject(s)
Chondrocalcinosis/diagnosis , Forefoot, Human/diagnostic imaging , Chondrocalcinosis/pathology , Chondrocalcinosis/surgery , Diagnosis, Differential , Forefoot, Human/surgery , Humans , Male , Middle Aged
16.
Planta ; 225(1): 153-64, 2006 Dec.
Article in English | MEDLINE | ID: mdl-16896794

ABSTRACT

The biosynthesis of seed oil and starch both depend on the supply of carbon from the maternal plant. The biochemical interactions between these two pathways are not fully understood. In the Arabidopsis mutant shrunken seed 1 (sse1)/pex16, a reduced rate of fatty acid synthesis leads to starch accumulation. To further understand the metabolic impact of the decrease in oil synthesis, we compared soluble metabolites in sse1 and wild type (WT) seeds. Sugars, sugar phosphates, alcohols, pyruvate, and many other organic acids accumulated in sse1 seeds as a likely consequence of the reduced carbon demand for lipid synthesis. The enlarged pool size of hexose-P, the metabolites at the crossroad of sugar metabolism, glycolysis, and starch synthesis, was likely a direct cause of the increased flow into starch. Downstream of glycolysis, more carbon entered the TCA cycle as an alternative to the fatty acid pathway, causing the total amount of TCA cycle intermediates to rise while moving the steady state of the cycle away from fumarate. To convert the excess carbon metabolites into starch, we introduced the Escherichia coli starch synthetic enzyme ADP-glucose pyrophosphorylase (AGPase) into sse1 seeds. Expression of AGPase enhanced net starch biosynthesis in the mutant, resulting in starch levels that reached 37% of seed weight. However, further increases above this level were not achieved and most of the carbon intermediates remained high in comparison with the WT, indicating that additional mechanisms limit starch deposition in Arabidopsis seeds.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Carbon/metabolism , Seeds/metabolism , Amino Acids/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Carbohydrate Metabolism/genetics , Carbohydrate Metabolism/physiology , Escherichia coli/genetics , Fatty Acids/metabolism , Gas Chromatography-Mass Spectrometry , Gene Expression Regulation, Plant , Glucose-1-Phosphate Adenylyltransferase/genetics , Glucose-1-Phosphate Adenylyltransferase/metabolism , Lipid Metabolism/genetics , Lipid Metabolism/physiology , Metabolic Networks and Pathways/genetics , Metabolic Networks and Pathways/physiology , Models, Biological , Plant Oils/metabolism , Plants, Genetically Modified , Recombinant Proteins/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Seeds/genetics , Starch/metabolism
17.
Proc Natl Acad Sci U S A ; 103(2): 472-6, 2006 Jan 10.
Article in English | MEDLINE | ID: mdl-16387852

ABSTRACT

We show that MAX1, a specific repressor of vegetative axillary bud outgrowth in Arabidopsis, acts a positive regulator of the flavonoid pathway, including 11 structural genes and the transcription factor An2. Repression of bud outgrowth requires MAX1-dependent flavonoid gene expression. As the flavonoidless state leads to lateral outgrowth in Arabidopsis, our data suggest that a flavonoid-based mechanism regulates axillary bud outgrowth and that this mechanism is under the control of MAX1. Flavonoid gene expression results in the diminished expression of auxin transporters in the bud and stem, and this, in turn, decreases the rate of polar auxin transport. We speculate that MAX1 could repress axillary bud outgrowth via regulating flavonoid-dependent auxin retention in the bud and underlying stem. Because MAX1 is implicated in synthesis of the carotenoid-derived branch regulator(s) from the root, it likely links long-distance signaling with local control of bud outgrowth.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/growth & development , Arabidopsis/metabolism , Flavonoids/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Biological Transport , Gene Expression Regulation, Plant , Indoleacetic Acids/metabolism , Phenotype , Plant Stems/genetics , Plant Stems/growth & development , Plant Stems/metabolism , Plants, Genetically Modified
18.
Planta ; 223(4): 779-84, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16231155

ABSTRACT

There are two independent pathways, the cytosolic mevalonate (MVA) pathway and the plastid nonmevalonate (nonMVA) pathway, to synthesize isopentenyl diphosphate and dimethylallyl diphosphate in plants. Carotenoids and the phytyl side chain of chlorophylls are isoprenoids derived from the plastid nonMVA pathway. All enzymes involved in the nonMVA pathway have been identified in Escherichia coli. The E. coli IspF protein catalyzes a unique cyclization reaction to convert 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate into 2-C-methyl-D-erythritol 2,4-cyclodiphosphate in the nonMVA pathway. We have characterized an Arabidopsis T-DNA insertion mutant, ispF-1, which has a null mutation in the IspF gene. Homozygous ispF-1 mutants are albino lethal and the IspF transcripts are undetectable in these plants. Moreover, the ispF-1 mutant chloroplasts are filled with vesicles instead of thylakoids. Amino acid sequence alignment reveals that the IspF proteins are highly conserved between plants and bacteria. Interestingly, expression of the Arabidopsis IspF protein can rescue the lethal phenotype of an E. coli ispF mutant. These results indicate that the Arabidopsis IspF may share similar enzymatic mechanisms with the E. coli protein.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Phosphorus-Oxygen Lyases/metabolism , Plastids/metabolism , Terpenes/metabolism , Arabidopsis/cytology , Arabidopsis/enzymology , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Chloroplasts/genetics , Chloroplasts/ultrastructure , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Plant , Phenotype , Phosphorus-Oxygen Lyases/genetics
19.
J Exp Bot ; 56(422): 3137-47, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16263907

ABSTRACT

A novel seven-transmembrane receptor family, that is comprised of human adiponectin receptors (AdipoRs) and membrane progestin receptors (mPRs) that share little sequence homology with all known G protein-coupled receptors (GPCRs), has been identified recently. Although a fish mPR has been suggested to be a GPCR, human AdipoRs seem to be structurally and functionally distinct from all known GPCRs. The identification of a novel gene family, the heptahelical protein (HHP) gene family, encoding proteins in Arabidopsis predicted to have a heptahelical transmembrane topology is reported here. There are at least five HHP genes in Arabidopsis whose encoded amino acid sequences have significant similarities to human AdipoRs and mPRs. The expression and regulation of the Arabidopsis HHP gene family has been studied here. The expression of the HHP gene family is differentially regulated by plant hormones. Steady-state levels of HHP1 mRNA are increased by treatments with abscisic acid and gibberellic acid, whereas levels of HHP2 mRNA are increased by abscisic acid and benzyladenine treatments. In addition, the expression of the HHP gene family is up-regulated by the presence of sucrose in the medium. Temperature and salt stress treatments also differentially affect the expression of the HHP genes. These novel seven-transmembrane proteins previously described in yeast and animals, and now identified in plants, may represent a new class of receptors that are highly conserved across kingdoms.


Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/genetics , Gene Expression Regulation, Plant , Membrane Proteins/genetics , Arabidopsis/drug effects , Arabidopsis/metabolism , Arabidopsis Proteins/chemistry , Arabidopsis Proteins/metabolism , Databases, Genetic , Gene Expression Profiling , Genes, Plant , Humans , Light , Membrane Proteins/chemistry , Membrane Proteins/metabolism , Multigene Family , Oligonucleotide Array Sequence Analysis , Plant Growth Regulators/pharmacology , Receptors, Cell Surface/chemistry , Receptors, Progesterone/chemistry , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Structural Homology, Protein , Sucrose/pharmacology
20.
Bull Hosp Jt Dis ; 62(3-4): 85-9, 2005.
Article in English | MEDLINE | ID: mdl-16022218

ABSTRACT

This is a retrospective review of nine coronal shear fractures of the distal humerus. Two were isolated fractures and seven were associated with other peri-articular elbow injuries, termed "complex" coronal shear fractures. All cases underwent immediate open reduction and internal fixation (ORIF) and were then followed for an average of 14 months (range: 6.5 to 23 months) with outcomes evaluated using the Mayo Elbow Performance Scoring system. There was a significant difference found between injuries limited to the radiocapitellar (RC) joint (isolated coronal shear fractures, or those associated only with radial head fractures) and the complex injuries extending beyond the RC joint. Scores for the RC injuries were 100 and other complex injuries had an average score of 69 (range: 35 to 95; p = .025). All complications were limited to the group with the complex injuries, including stiffness, nonunion, pain, and gross instability. Much of the current thinking in treatment of this fracture was upheld in this study; computed tomography aids in diagnosis, ORIF is a necessity, and there is a need for anatomic reduction. When a coronal shear fracture is complicated by a concomitant injury outside the RC joint, both the surgeon's and patient's expectation need to be adjusted accordingly.


Subject(s)
Humeral Fractures/surgery , Adolescent , Adult , Aged , Female , Fracture Fixation, Internal , Humans , Humeral Fractures/diagnosis , Humeral Fractures/diagnostic imaging , Male , Middle Aged , Tomography, X-Ray Computed , Elbow Injuries
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