Metabolic engineering to increase isoflavone biosynthesis in soybean seed.

Isoflavone levels in Glycine max (soybean) were increased via metabolic engineering of the complex phenylpropanoid biosynthetic pathway. Phenylpropanoid pathway genes were activated by expression of the maize C1 and R transcription factors in soybean seed, which decreased genistein and increased the daidzein levels with a small overall increase in total isoflavone levels. Cosuppression of flavanone 3-hydroxylase to block the anthocyanin branch of the pathway, in conjunction with C1/R expression, resulted in higher levels of isoflavones.

Effects of disease management programs on functional status of patients with rheumatoid arthritis.

Objective: To perform a systematic review of the published literature on disease management of rheumatoid arthritis (RA) and to use meta-analysis to estimate the magnitude of benefit these programs have on functional status in patients with RA.

Methods: Computerized databases for English articles from 1966 to September 2001 were searched. Two reviewers evaluated 1,029 published titles, identified 11 studies meeting explicit inclusion criteria, and extracted data about study characteristics, interventions used, and outcomes measured.

Is there still a role for traditional disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis?

Rheumatoid arthritis is a chronic and debilitating disease, affecting an estimated 1% of the population worldwide. The past decade has witnessed an explosion in our understanding of the pathophysiology of rheumatoid arthritis and therefore in our ability to more effectively target the disease process. Although a cure remains elusive, remission is an approachable goal.

Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: results of a two-year, randomized, double-blind, placebo-controlled trial.

Objective: To compare the efficacy of combination therapy with methotrexate (MTX) and hydroxychloroquine (HCQ), MTX and sulfasalazine (SSZ), and MTX, HCQ, and SSZ in patients with rheumatoid arthritis (RA).

Methods: RA patients (n = 171) who had not previously been treated with combinations of the study medications were randomized to receive 1 of the 3 treatment combinations in this 2-year, double-blind, placebo-controlled protocol. HCQ was given at a dosage of 200 mg twice a day.

Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison of minocycline and hydroxychloroquine.

Objective: To compare the efficacy of minocycline with that of a conventional disease-modifying antirheumatic drug (DMARD), hydroxychloroquine, in patients with early seropositive rheumatoid arthritis (RA).

Methods: Sixty patients with seropositive RA of <1 year's duration who had not been previously treated with DMARDs were randomized to receive minocycline, 100 mg twice per day, or hydroxychloroquine, 200 mg twice per day, in a 2-year, double-blind protocol. All patients also received low-dose prednisone.

Treatment of relapse after autologous blood stem cell transplantation for severe rheumatoid arthritis.

There is little information about the clinical course of patients with rheumatoid arthritis (RA) who relapse after autologous blood stem cell transplantation (ASCT). We describe 6 patients with severe RA who received ASCT in 3 US centers. Duration of followup was between 24 and 42 months posttransplant.

Intensive immunoablation and autologous blood stem cell transplantation in patients with refractory rheumatoid arthritis: the University of Nebraska experience.

Two patients with severe rheumatoid arthritis (RA) were treated with high dose chemotherapy and autologous blood stem cell transplantation. Hematopoietic stem cells mobilized readily with cyclophosphamide and granulocyte-colony stimulating factor. Both patients achieved an American College of Rheumatology (ACR) 50% response before starting high dose therapy.

Evaluation and documentation of rheumatoid arthritis disease status in the clinic: which variables best predict change in therapy.

To determine in clinical practice which rheumatoid arthritis (RA) clinical status variables are most associated with a change in disease modifying antirheumatic drug (DMARD) therapy, we studied 26,240 observations from 1905 RA patients occurring over 25 years. Variables included tender joint count, erythrocyte sedimentation rate (ESR), grip strength, visual analog scale for pain, global severity, fatigue and sleep, Health Assessment Question functional disability scale (HAQ), anxiety, depression and morning stiffness. Only the tender joint count required a physician.

Conventional DMARD options for patients with a suboptimal response to methotrexate.

Methotrexate (MTX) is one of the disease modifying antirheumatic drugs (DMARD) commonly used to treat rheumatoid arthritis (RA). However, MTX therapy alone rarely results in remission and frequently does not even produce 50% improvement. Therefore, over the course of their disease, many patients will require additional therapy to manage their clinical symptoms.

Evaluating severity and status in rheumatoid arthritis.

There is general agreement regarding the most appropriate examinations and methods to use to evaluate change in status in randomized controlled trials (RCT). However, no guidelines exist to aid in determining and evaluating actual status rather than change in status, particularly when applied to individual patients with rheumatoid arthritis (RA). In addition, methods appropriate for clinical trials may not be useful in evaluating individual patients because of time constraints.

Combinations of conventional disease-modifying antirheumatic drugs.

During the last decade, numerous new treatments and treatment approaches have literally transformed current thinking about rheumatoid arthritis (RA) and, more importantly, about the way patients are treated. The nearly universal acceptance of the use of combinations of disease-modifying antirheumatic drugs (DMARDs) to more effectively treat a growing percentage of patients with RA has been a central theme. Importantly, controlled studies have now shown many combinations to be well tolerated and significantly more effective than mono-DMARD therapy.

How is it best to treat early rheumatoid arthritis patients?

During the past decade, many important changes have occurred in the treatment of rheumatoid arthritis, perhaps the most important of which has been the realization that early diagnosis and early treatment are critical. This has challenged our health-care systems to make sure that patients with early arthritis have access to the appropriate physicians. Additionally, the last decade has also seen many new treatment options become available for patients with rheumatoid arthritis.

Cervical and thoracic components of multiorgan lymphangiomatosis managed surgically.

We report a patient who presented for management of suspected metastatic carcinoma of unknown origin. The lesions proved to be lymphangiomatosis involving multiple organ systems. Surgical management of the thoracic and cervical components of this rare condition is described.

Fractured occluder disc: a previously unrecognized complication of the Starr-Edwards disc prosthesis.

Fracture of the occluder disc of a low-profile Starr-Edwards prosthesis is a hitherto unrecognized complication. We describe a patient who presented with right heart failure and severe pulmonary hypertension 27 years after mitral valve replacement with a model 6520 caged-disc prosthesis. At surgery, there was a longitudinal split in the occluder disc, and organized thrombus was lodged between the split segments.

Multiple lung abscesses due to Ochroconis gallopavum, a dematiaceous fungus, in a nonimmunocompromised wood pulp worker.

An occurrence of multiple chronic lung abscesses managed by lobectomy is described. These abscesses were present for 13 years in the patient, a nonimmunocompromised wood pulp worker. The patient had hemoptysis at presentation.

Production of the isoflavones genistein and daidzein in non-legume dicot and monocot tissues.

Metabolic engineering for production of isoflavones in non-legume plants may provide the health benefits of these phytoestrogens from consumption of more widely used grains. In legumes, isoflavones function in both the symbiotic relationship with rhizobial bacteria and the plant defense response. Expression of a soybean isoflavone synthase (IFS) gene in Arabidopsis plants was previously shown to result in the synthesis and accumulation of the isoflavone genistein in leaf and stem tissue (Jung et al.