Inhibition of cell growth and macromolecule biosynthesis of human promyelocytic leukemic cells by acridone alkaloids

Acridone alkaloids of plants indigenous to the Orient were isolated and purified, and their chemical structures were determined. A total of 50 acridones and their synthetic derivatives were subjected to rapid screening for inhibition of macromolecular synthesis using radiolabeled precursors of DNA, RNA and protein. These compounds were then studied to examine cell growth inhibition of human promyelocytic leukemic cells (HL-60). Cytotoxicity was studied using the trypan blue exclusion method. Of 50 compounds evaluated for cell growth inhibition, 12 compounds showed IC₅₀<10 μM; 12 compounds, 10-20 μM; 8 compounds, 20-100 μM; and 18 compounds, >100 μM.     

The value of electrodiagnostic consultation for patients with upper extremity nerve complaints: a prospective comparison with the history and physical examination.

OBJECTIVES: To determine whether electrodiagnostic testing changes diagnostic certainty compared with a detailed history and physical examination, and whether interactions between medical information, the extent of testing, and diagnostic certainty imply a need for advanced medical knowledge on the part of the tester. DESIGN: Prospective observation. SETTING: University orthopedic department and small community hospital electrodiagnostic laboratories. PATIENTS: Two hundred fifty-five consecutive referrals for upper extremity nerve complaints. OUTCOME MEASURES: Diagnosis, diagnostic confidence, and severity of neurologic lesion were coded after standardized history and physical and after electrodiagnostic testing. RESULTS: Electrodiagnostic testing substantially altered 42% of diagnoses, confirmed 37%, and did not clarify 21%. The extent of testing correlated with the size of the differential diagnosis, the number of previous hospitalizations, and the number of other medical problems. Confidence in final diagnoses correlated positively with severity of the lesion, but negatively with the size of the differential diagnosis and the number of painful body areas. Hospitalizations and medical problems also tended towards negative correlations. CONCLUSIONS: This study, in which all electrodiagnostics, histories, and physical examinations were performed by a single physician, suggests that electrodiagnosis substantially alters clinical impressions in a large percentage of patients. The complex relationship between clinical information, the extent of testing, and final diagnostic certainty suggests that specialized medical knowledge is required for accurate electrodiagnosis.     

The comparative responses of human polymorphonuclear leukocytes obtained by counterflow centrifugal elutriation and Ficoll-Hypaque density centrifugation. I. Resting volume, stimulus-induced superoxide production, and primary and specific granule release

Standard isolation techniques for the human polymorphonuclear leukocyte (PMN) involve sequential exposure of cells to the nonphysiologic environments of dextran, Ficoll-Hypaque (FH) gradient centrifugation, and hypotonic conditions. It has been suggested that these may be harmful to the recovered PMN. Counterflow centrifugal elutriation (CCE) allows separation of human PMNs while the cells are continuously bathed in a physiologic and isotonic buffer. To investigate whether preparative technique may alter PMN activation, we compared PMNs obtained by these two methods for stimulus-induced superoxide production and release of primary and specific granule contents. Resting PMN volume was also evaluated. We observed that PMNs obtained using the CCE method were larger and released significantly more superoxide and specific granule contents than PMNs obtained by the standard FH technique. The possible origins for these differences are discussed.     

Use of split‐thickness plantar skin grafts in the management of leg and foot skin defects

The basic principle of donor site selection is to take skin from areas that will heal with minimal scarring while balancing the needs of the recipient site. For skin loss from the lower legs and feet, the most common harvest site for split‐thickness skin grafts is the anterior or posterior thigh; grafts from the plantar areas have been mostly used to cover the volar aspect of digits and palms. Between September 2015 and September 2017, 42 patients with areas of skin loss on the legs or feet were treated with plantar skin grafts because of their cosmetic benefits and the convenience of the surgical procedure and postoperative wound care. Our technique of harvesting a single layer of split‐thickness skin graft (0.014 in. thick) from a non‐weight‐bearing area of the foot of the injured leg is simple and provided good functional and cosmetic outcomes at both the donor and recipient sites. All patients were very satisfied with the recovery progress and final results. Therefore, in the management of skin defects in the lower legs or feet that comprise less than 1.5% of the total body surface area, our surgical method is a reliable alternative to anterior or posterior thigh skin grafting.     

Toward reliable retrieval of functional information of papillary dermis using spatially resolved diffuse reflectance spectroscopy

Spatially resolved diffuse reflectance spectroscopy (SRDRS) has been employed to quantify tissue optical properties and its interrogation volume is majorly controlled by the source-to-detector separations (SDSs). To noninvasively quantify properties of dermis, a SRDRS setup that includes SDS shorter than 1 mm is required. It will be demonstrated in this study that Monte Carlo simulations employing the Henyey-Greenstein phase function cannot always precisely predict experimentally measured diffuse reflectance at such short SDSs, and we speculated this could be caused by the non-negligible backward light scattering at short SDSs that cannot be properly modeled by the Henyey-Greenstein phase function. To accurately recover the optical properties and functional information of dermis using SRDRS, we proposed the use of the modified two-layer (MTL) geometry. Monte Carlo simulations and phantom experiment results revealed that the MTL probing geometry was capable of faithfully recovering the optical properties of upper dermis. The capability of the MTL geometry in probing the upper dermis properties was further verified through a swine study, and it was found that the measurement results were reasonably linked to histological findings. Finally, the MTL probe was utilized to study psoriatic lesions. Our results showed that the MTL probe was sensitive to the physiological condition of tissue volumes within the papillary dermis and could be used in studying the physiology of psoriasis.OCIS codes: (170.5280) Photon migration, (170.3660) Light propagation in tissues, (170.7050) Turbid media     

Deficiency of electroneutral K+–Cl− cotransporter 3 causes a disruption in impulse propagation along peripheral nerves

Nerve conduction requires the fine tuning of ionic currents through delicate interactions between axons and Schwann cells. The K⁺–Cl⁻ cotransporter (KCC) family includes four isoforms (KCC1–4) that play an important role in the maintenance of cellular osmotic homeostasis via the coupled electroneutral movement of K⁺ and Cl⁻ with concurrent water flux. Mutation in SLC12A6 gene encoding KCC3 results in an autosomal recessive disease, known as agenesis of the corpus callosum associated with peripheral neuropathy. Nevertheless, the role of KCC3 in nerve function remains a puzzle. In this study, the microscopic examination of KCC isoforms expressed in peripheral nerves showed high expression of KCC2–4 in nodal segments of the axons and in the perinucleus and microvilli of Schwann cells. The KCC inhibitor [[(dihydroindenyl)oxy]alkanoic acid] but not the Na⁺–K⁺–2Cl⁻‐cotransport inhibitor (bumetanide) dose‐dependently suppressed the amplitude and area of compound muscle action potential, indicating the involvement of KCC activity in peripheral nerve conduction. Furthermore, the amplitude and area under the curve were smaller, and the nerve conduction velocity was slower in nerves from KCC3^−/− mice than in nerves from wild‐type mice, while the expression pattern of KCC2 and KCC4 was similar in KCC3 kockout and wild‐type strains. KCC3^−/− mice also manifested a prominent motor deficit in the beam‐walking test. This is the first study to demonstrate that the K⁺–Cl⁻ cotransporter activity of KCC3 contributes to the propagation of action potentials along peripheral nerves. © 2010 Wiley‐Liss, Inc.     

Adjuvant oxaliplatin- or irinotecan-containing chemotherapy improves overall survival following resection of metachronous colorectal liver metastases

Purpose  

Adjuvant systemic 5-fluorouracil (5-FU)-based chemotherapy improves survival after resection of synchronous colorectal liver metastases (CLMs), but not metachronous. We retrospectively examined if adjuvant chemotherapy with new regimen containing oxaliplatin or irinotecan improved survivals after resection of metachronous CLMs.