Biomedical subjects

Richard Stark

Publications and source records attributed to Richard Stark.

5 recordsLinked to original sources

PubMed2024

A distinct, high-affinity, alkaline phosphatase facilitates occupation of P-depleted environments by marine picocyanobacteria.

Marine picocyanobacteria of the genera Prochlorococcus and Synechococcus, the two most abundant phototrophs on Earth, thrive in oligotrophic oceanic regions. While it is well known that specific lineages are exquisitely adapted to prevailing in situ light and temperature regimes, much less is known of the molecular machinery required to facilitate occupancy of these low-nutrient environments. Here, we describe a hitherto unknown alkaline phosphatase, Psip1, that has a substantially higher affinity for phosphomonoesters than other well-known phosphatases like PhoA, PhoX, or PhoD and is restricted to clade III Synechococcus and a subset of high light I-adapted Prochlorococcus strains, suggesting niche specificity. We demonstrate that Psip1 has undergone convergent evolution with PhoX, requiring both iron and calcium for activity and likely possessing identical key residues around the active site, despite generally very low sequence homology. Interrogation of metagenomes and transcriptomes from TARA oceans and an Atlantic Meridional transect shows that psip1 is abundant and highly expressed in picocyanobacterial populations from the Mediterranean Sea and north Atlantic gyre, regions well recognized to be phosphorus (P)-deplete. Together, this identifies psip1 as an important oligotrophy-specific gene for P recycling in these organisms. Furthermore, psip1 is not restricted to picocyanobacteria and is abundant and highly transcribed in some α-proteobacteria and eukaryotic algae, suggesting that such a high-affinity phosphatase is important across the microbial taxonomic world to occupy low-P environments.

Alkaline Phosphatase↗

PubMed2006

Development of neuropathy in patients with myeloma treated with thalidomide: patterns of occurrence and the role of electrophysiologic monitoring.

PURPOSE: Peripheral neuropathy frequently limits the duration of treatment with thalidomide for patients with multiple myeloma. We assessed the time course of occurrence, possible predictive factors, and the utility of serial nerve electrophysiological studies (NES) for detecting onset of neuropathy. PATIENTS AND METHODS: Seventy-five patients with relapsed/refractory myeloma were enrolled onto a multicenter trial of dose-escalating thalidomide with or without interferon. Patients underwent clinical assessment plus NES at baseline and every 3 months. Time to development of neuropathy according to clinical or NES criteria was compared. Patient and treatment-related factors were compared as predictors of neuropathy. RESULTS: Thirty-nine percent had some NES abnormalities at baseline. Patients received thalidomide at a median dose-intensity of 373 mg/d. Thirty-one of 75 patients (41%) developed neuropathy during thalidomide treatment; 11 patients (15%) discontinued treatment with thalidomide due to neuropathy. The actuarial incidence of neuropathy increased from 38% at 6 months to 73% at 12 months, with 81% of responding patients developing this complication. Serial NES did not reliably predict the imminent development of clinical neuropathy requiring thalidomide cessation, nor were patient age, sex, or prior therapy predictive. Patients who developed neuropathy had a longer duration of thalidomide exposure (median, 268 v 89 days; P = .0001). Cumulative dose or dose-intensity received was not predictive. CONCLUSION: The majority of patients will develop peripheral neuropathy given sufficient length of treatment with thalidomide. To minimize the risk of neurotoxicity, therapy should be limited to less than 6 months. Electrophysiologic monitoring provides no clear benefit versus careful clinical evaluation for the development of clinically significant neuropathy.

Aged↗

PubMed2006

Dynamic targeting image-guided radiotherapy.

Volumetric imaging and planning for 3-dimensional (3D) conformal radiotherapy and intensity-modulated radiotherapy (IMRT) have highlighted the need to the oncology community to better understand the geometric uncertainties inherent in the radiotherapy delivery process, including setup error (interfraction) as well as organ motion during treatment (intrafraction). This has ushered in the development of emerging technologies and clinical processes, collectively referred to as image-guided radiotherapy (IGRT). The goal of IGRT is to provide the tools needed to manage both inter- and intrafraction motion to improve the accuracy of treatment delivery. Like IMRT, IGRT is a process involving all steps in the radiotherapy treatment process, including patient immobilization, computed tomography (CT) simulation, treatment planning, plan verification, patient setup verification and correction, delivery, and quality assurance. The technology and capability of the Dynamic Targeting IGRT system developed by Varian Medical Systems is presented. The core of this system is a Clinac or Trilogy accelerator equipped with a gantry-mounted imaging system known as the On-Board Imager (OBI). This includes a kilovoltage (kV) x-ray source, an amorphous silicon kV digital image detector, and 2 robotic arms that independently position the kV source and imager orthogonal to the treatment beam. A similar robotic arm positions the PortalVision megavoltage (MV) portal digital image detector, allowing both to be used in concert. The system is designed to support a variety of imaging modalities. The following applications and how they fit in the overall clinical process are described: kV and MV planar radiographic imaging for patient repositioning, kV volumetric cone beam CT imaging for patient repositioning, and kV planar fluoroscopic imaging for gating verification. Achieving image-guided motion management throughout the radiation oncology process requires not just a single product, but a suite of integrated products to manipulate all patient data, including images, efficiently and effectively.

Humans↗

PubMed2002

Detection of a non-Hodgkin's lymphoma by capromab pendetide scintigraphy (ProstaScint) in a patient with prostate carcinoma.

A 77-year-old man with Gleason score 7 prostate cancer, after radical prostatectomy, in whom the prostate-specific antigen level increased to 5.0 ng/mL 8 years later, underwent a ProstaScint scan. Radiotracer deposition was noted in the prostatic "fossa," highly suspicious of recurrence. An additional focus in the mid abdomen was suspicious of adenopathy. Computed tomography disclosed an abdominal mass that, at biopsy, proved to be a malignant B-cell lymphoma. That lesion resolved after chemotherapy, and the prostate-specific antigen level substantially decreased with hormonal treatment. The possible association of prostate cancer and lymphoma is discussed.

Aged↗

PubMed2002

CNS listeriosis confused with leptomeningeal carcinomatosis in a patient with a malignant insulinoma.

We describe a case of presumed listeria monocytogenes rhomboencephalitis, which was initially confused with leptomeningeal carcinomatosis in a patient with a malignant carcinoid tumor. Long-term corticosteroid treatment and immunosuppression caused by malignancy predisposed the patient to developing listeriosis. The clinical and radiologic features of this illustrative case are described. Listeriosis is an important treatable differential diagnosis in patients with malignancy presenting with neurologic signs.

Adult↗