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Biomedical subjects

R L Nelson

Publications and source records attributed to R L Nelson.

At least 127 records · Page 7Linked to original sources

Antitumor activity of vinzolidine in the human tumor clonogenic assay and comparison with vinblastine.

Vinzolidine (VZL), a semisynthetic vinblastine (VLB) derivative, was tested against a variety of solid tumors in the human tumor clonogenic assay (HTCA). The emphasis was on continuous drug exposure because of the schedule-dependency of the vincas and long half-life of VZL. Of tumor types with more than ten samples tested, the percentage of cases exhibiting inhibition (50% or less of control) of tumor colony forming units (TCFU) was as follows: melanoma (48%), lung cancer (48%), breast cancer (40%), renal cancer (33%), and ovarian cancer (24%). In tumor types tested less frequently, inhibition of TCFU after continuous or one hour drug exposure was observed in 2/7 colon cancers, 1/3 pancreatic cancers and 3/4 gastric cancers. Paired analysis of tumors tested to both VZL and VLB demonstrated no significant difference in overall activity of these two vinca alkaloids. VZL appears to be a promising drug for clinical trials, with in vitro activity in melanoma, lung and breast cancers. More interesting is the suggestion of activity in gastrointestinal tumors, especially colon cancer which is generally resistant to drugs in the HTCA and in vivo.

Antineoplastic Agents↗

Is the changing pattern of colorectal cancer caused by selenium deficiency?

An hypothesis is presented to explain the changing pattern of colorectal cancer seen within the United States and other western countries in the last 30 years, the simultaneous increase of right-sided colonic cancer and disappearance of rectal cancer. Review of experimental and epidemiologic data suggests that this change may be due to a new systemic deficiency of the trace element, selenium. This deficiency has arisen not just from decreased consumption of selenium in the last 30 years, but also from increased consumption of zinc and fluoride, which may antagonize the effect of selenium.

Animals↗

Identification, purification, and characterization of phosphotyrosine-specific protein phosphatases from cultured chicken embryo fibroblasts.

Tyrosine phosphorylation catalyzed by a unique class of protein kinases is an important process in both normal cell proliferation and oncogenic transformation. In this study, phosphoprotein phosphatases specific for the dephosphorylation of phosphotyrosine residues were partially purified from secondary chicken embryo fibroblasts, using 32P-labeled immunoglobulin G phosphorylated by pp60src as substrate. Crude cell extracts contained ca. 70% of the activity in the soluble form and ca. 30% associated with a crude membrane fraction. The soluble activity was purified by using DEAE-cellulose and carboxymethyl cellulose column chromatography and gel filtration, and at least three enzyme species of apparent Mr 55,000 (pTPI), 50,000 (pTPII), and 95,000 (pTPIII)--comprising ca. 20, 45, and 35%, respectively, of the total activity--were resolved. All three enzymes possessed somewhat similar properties. They had a pH optimum of about 7.4, they were inhibited by Zn2+, vanadate, ATP, and ADP, and they were unaffected by divalent metal cations, EDTA, and F- under standard assay conditions employing a physiological ionic strength. These properties suggest that they represent a class of enzymes distinct from well-known phosphoseryl-phosphothreonyl-protein phosphatases and that dephosphorylation of phosphotyrosine-containing proteins may be carried out by a unique family of phosphoprotein phosphatases. Transformation by Rous sarcoma virus resulted in a small increase in phosphotyrosyl-protein phosphatase activity.

Animals↗

Chlamydial proctitis--unusual presentation as a symptomatic vaginal mass.

Chlamydial cervicitis and salpingitis are being increasingly diagnosed and reported, but chlamydial proctitis is an unusual problem to be found in gynecologic practice. In the reported patient who gave a history of rectal intercourse and presented with a symptomatic vaginal mass, a diagnosis of chlamydial proctitis was made on the basis of biopsy histology, specific monoclonal antibody-immunoperoxidase chlamydia assay, and response to doxycycline therapy.

Adult↗

Colony transformation in C3H 10T1/2 cells: stepwise development of neoplastic change in vitro.

This report demonstrates that low passage C3H 10T1/2 cells treated with the carcinogens benzo(a)pyrene or diepoxybutane are transformed morphologically as colonies in as little as 14 d after carcinogen treatment. A transforming dose-response curve is achieved but the frequency of transformation is less than half the expected for 38 d foci, compared on the basis of percent transformants per cell plated. Anchorage-independent cell growth, plating efficiency, doubling time, cell density, and modal chromosomal number were examined from transformed colonies and foci. The data from colony transformants show progressive alteration of these in vitro expressions of neoplastic character with continued subcultivation, consistent with the multistep hypothesis of carcinogenesis. Early in vivo data obtained from one colony-derived transformed cell line show tumorigenesis in irradiated mice within 13 wk of implantation. With continued in vivo passage, tumors were observed in 4 to 6 wk.

Animals↗

Rapid inoculum standardization system: a novel device for standardization of inocula in antimicrobial susceptibility testing.

A rapid inoculum standardization system for antimicrobial susceptibility testing without incubation or the conventional turbidity adjustment has been developed. The rapid inoculum standardization system consists of a plastic rod with cross-hatched grooves on one end and a specific nutrient medium in a vial. The crosshatched grooves are designed to pick up and release a known number of viable microorganisms. In use, the end of the rod is touched to five colonies 1 to 2 mm in diameter from a primary agar plate, thus filling the grooves with bacteria. The rod is placed into the vial, and the bacteria are suspended in the medium by agitation with a Vortex Genie Mixer. The resulting suspension contains 5 X 10(7) to 5 X 10(8) CFU/ml for most gram-negative bacilli and gram-positive cocci. Microorganisms such as streptococci that have colonies less than 1 mm in diameter require as many as 10 colonies for an adequate inoculum suspension. Ninety-five commonly encountered bacterial isolates were tested in triplicate by agar plate counts. The resulting overall geometric mean of the agar plate counts was 1.52 X 10(8) CFU/ml for the species tested. We have found that the rapid inoculum standardization system provides a consistent and reproducible method for the standardization of inoculum for antimicrobial susceptibility testing without the incubation period and turbidity adjustment.

Anti-Bacterial Agents↗

The comparative clinical pharmacology and pharmacokinetics of vindesine, vincristine, and vinblastine in human patients with cancer.

The pharmacokinetics of vindesine, vincristine, and vinblastine were investigated in patients with cancer. All drugs were administered rapidly via intravenous injection, and drug levels were determined in serum obtained at intervals after injection by radioimmunoassay. All three drugs exhibited a triphasic serum decay pattern, with no major differences in alpha or beta phase half-lives noted among them. However, vincristine had a longer and more variable terminal phase half-life (85 +/- 69 hr) than vindesine (24 +/- 10 hr) or vinblastine (25 +/- 7 hr). Central compartment volumes were also different. The most important finding was the observation of differences in the serum or body clearances of these drugs (vincristine 0.106 liter/kg/hr, vindesine 0.252 liter/kg/hr, and vinblastine 0.740 liter/kg/hr). These differences correlate well with the results of similar studies done in animals, with acute LD50 data in mice, and with the usually employed weekly clinical doses for these drugs. These findings support the hypothesis that differences in the toxicities of these alkaloids may be related in part to differences in their pharmacokinetics.

Drug Therapy, Combination↗

Ischemic proctitis.

The rectum is rarely involved in ischemic colitis because of its abundant collateral blood supply. Thus, other forms of inflammatory intestinal disease, such as antibiotic associated or infectious colitis, are considered to be more likely if the rectum is inflamed. Yet, collateral flow develops slowly. Therefore, ischemic proctitis does occur in instances of sudden occlusion of the major blood supply to the rectum, such as after an aortic operation. The histopathology of this condition does not differ from that of infectious colitides, and the diagnosis of ischemic colitis can only be confirmed after careful culturing and assessment of the stool for clostridial toxins. Penile Doppler pressure measurements, as demonstrated in the patient presented herein, may be a simple, noninvasive method of inferring rectal blood flow and, therefore, aid in the diagnosis of ischemic proctitis.

Biopsy↗

The association of carcinoid tumors of the rectum with myelofibrosis: report of two cases.

Two patients with myelofibrosis, a primary malignancy of the hematopoietic system, have developed carcinoid tumors of the rectum. This development is rare, as rectal carcinoids are more often associated with other carcinomas of the gastrointestinal tract. Rectal carcinoid tumors are, in general, less commonly associated with second malignancies than are carcinoid tumors of foregut and midgut origin.

Anus Neoplasms↗

Are elevated pancreatic polypeptide levels in patients with insulinoma secondary to hypoglycaemia?

In 13 patients with insulinoma, human pancreatic polypeptide (hPP) was measured under basal conditions, after a mixed meal, and during a fast of up to 72 h. Significant negative correlatons between hPP and plasma-glucose levels were found both under basal conditions and during fasting. Patients with insulinoma and basal plasma-glucose values above 60 mg/dl had hPP values similar to those in control subjects, whereas insulinoma patients with plasma-glucose values under 60 mg/dl had significantly higher hPP values (323 versus 115 pg/ml). The mean hPP response to a mixed meal was similar in patients with insulinoma and in control subjects. hPP values during symptomatic hypoglycaemia were higher in insulinoma patients than controls fasted for comparable times (751 versus 171 pg/ml). Under conditions of euglycaemia, hPP is not a reliable marker for insulinoma.

Adenoma, Islet Cell↗

Use of adrenal biopsy in diagnosing adrenoleukomyeloneuropathy.

A 22-year-old man was seen with Addison's disease, psychosis, and neurologic abnormalities. A tentative diagnosis of adrenoleukomyeloneuropathy was made. Because of his age, negative family history, and the potentially serious prognosis of this disorder, the diagnosis was verified with an adrenal biopsy. We believe this procedure is the method of choice in confirming the sporadic, atypical case of adrenoleukomyeloneuropathy.

Addison Disease↗

Mezlocillin pharmacokinetics in renal impairment.

Mezlocillin kinetics was examined in 28 adult subjects with varying renal function. Mezlocillin 3 gm, was infused over 30 min. Mean peak plasma concentrations ranged from 204 to 253 mg/I. When the area under the curve (AUC) was plotted against creatinine clearance (CCr), the relationship found was expressed by the equation AUC = 656e(-0.01)(CCr). From this relationship a dosage nonogram was derived describing a power function with the following equaton: Dose fraction = 1.32--e(-0.01)(CCr). Therapeutic guidelines are suggested.

Adult↗