Biomedical subjects

N M Price

Publications and source records attributed to N M Price.

At least 19 recordsLinked to original sources

PubMed2003

The biogeochemical cycles of trace metals in the oceans.

Planktonic uptake of some essential metals results in extraordinarily low concentrations in surface seawater. To sequester or take up these micronutrients, various microorganisms apparently release strong complexing agents and catalyze redox reactions that modify the bioavailability of trace metals and promote their rapid cycling in the upper water column. In turn, the low availability of some metals controls the rate of photosynthesis in parts of the oceans and the transformation and uptake of major nutrients such as nitrogen. The extremely low concentrations of several essential metals are both the cause and the result of ultraefficient uptake systems in the plankton and of widespread replacement of metals by one another for various biochemical functions.

Animals↗

PubMed2002

Differential regulation of MMP-1/9 and TIMP-1 secretion in human monocytic cells in response to Mycobacterium tuberculosis.

In tuberculosis, matrix metalloproteinase (MMP) secretion is involved in leukocyte migration to sites of infection but in excess may contribute to tissue destruction. We demonstrate that human monocytic THP-1 cells and primary monocytes secrete MMP-1 (52 kD collagenase) when phagocytosing live, virulent M. tuberculosis but not inert latex. The magnitude of MMP-1 secretion was approximately 10-fold less when compared to MMP-9 (92 kD gelatinase) secretion. MMP-1 secretion was also relatively delayed (detected at 24 h vs. 4 h). M. tuberculosis, zymosan or latex stimulate similar TIMP-1 secretion within 8 h and increasing over 24 h. MMP-1/9 secretion was decreased by inhibitors of protein kinase (PK) C, PKA or tyrosine kinases (PTK) in a concentration-dependent manner. In contrast, TIMP-1 secretion was not affected by PKC or PTK blockade and only somewhat reduced by high level PKA inhibition. In summary, M. tuberculosis-infected monocytes secrete MMP-1 at lower concentrations than MMP-9 and such MMP secretion is regulated by multiple upstream signalling pathways which do not control TIMP-1 secretion. Divergent effects of i on MMP and TIMP secretion from monocytes may be important in influencing matrix degradation in vivo.

Carbazoles↗

PubMed2001

Identification of a matrix-degrading phenotype in human tuberculosis in vitro and in vivo.

Tuberculous meningitis is characterized by cerebral tissue destruction. Monocytes, pivotal in immune responses to Mycobacterium tuberculosis, secrete matrix metalloproteinase-9 (MMP-9), which facilitates leukocyte migration across the blood-brain barrier, but may cause cerebral injury. In vitro, human monocytic (THP-1) cells infected by live, virulent M. tuberculosis secreted MMP-9 in a dose-dependent manner. At 24 h, MMP-9 concentrations increased 10-fold to 239 +/- 75 ng/ml (p = 0.001 vs controls). MMP-9 mRNA became detectable at 24--48 h. In contrast, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) gene expression and secretion were similar to constitutive levels from controls at 24 h and increased just 5-fold by 48 h. In vivo investigation revealed MMP-9 concentration per leukocyte in cerebrospinal fluid (CSF) from tuberculous meningitis patients (n = 23; median (range), 3.19 (0.19--31.00) ng/ml/cell) to be higher than that in bacterial (n = 12; 0.23 (0.01--18.37) ng/ml/cell) or viral meningitis (n = 20; 0.20 (0.04--31.00) ng/ml/cell; p < 0.01). TIMP-1, which was constitutively secreted into CSF, was not elevated in tuberculous compared with bacterial meningitis or controls. Thus, a phenotype in which MMP-9 activity is relatively unrestricted by TIMP-1 developed both in vitro and in vivo. This is functionally significant, since MMP-9 concentrations per CSF leukocyte (but not TIMP-1 concentrations) were elevated in fatal tuberculous meningitis and in patients with signs of cerebral tissue damage (unconsciousness, confusion, or neurological deficit; p < 0.05). However, MMP-9 activity was unrelated to the severity of systemic illness. In summary, M. tuberculosis-infected monocytic cells develop a matrix-degrading phenotype, which was observed in vivo and relates to clinical signs reflecting cerebral injury in tuberculous meningitis.

Adult↗

PubMed2001

Issues of normal tissue toxicity in patient and animal studies--effect of carbogen breathing in rats after 5-fluorouracil treatment.

Non-invasive magnetic resonance spectroscopy (MRS) can be used in the clinic to monitor the pharmacokinetics of the chemotherapeutic drug 5-fluorouracil (5-FU) and the effects of modifiers. We report two studies of 5-FU toxicity in normal tissue--one with patients and the other an animal study. 1) 19F MRS signals from fluoronucleotides, cytotoxic anabolites of 5-FU metabolism, were observed in the livers of two patients treated with 5-FU for colorectal cancer, shown by computed tomography (CT) and ultrasound (US) to have no liver metastases. This is the first report of non-invasive monitoring of toxic 5-FU metabolites in normal human tissues. 2) In animals, carbogen-breathing enhances tumour uptake and the efficacy of 5-FU, and the method is under trial in patients. This study demonstrates that there were no significant effects of carbogen breathing on the levels of 5-FU and its metabolites in normal rat tissues, or on the histology of the tissues assessed after treatment.

Adenocarcinoma↗

PubMed1994

Phytochelatin production by marine phytoplankton at low free metal ion concentrations: laboratory studies and field data from Massachusetts Bay.

Phytochelatins are small metal-binding polypeptides synthesized by algae in response to high metal concentrations. Using a very sensitive HPLC method, we have quantified phytochelatins from phytoplankton in laboratory cultures at environmentally relevant metal concentrations and in marine field samples. Intracellular concentrations of phytochelatin, in the diatom Thalassiosira weissflogii, exhibit a distinct dose-response relation with free Cd2+ concentration in the medium--not with total Cd(2+)--and are detectable even when the free Cd2+ concentration is less than 1 pM. In Massachusetts Bay, phytochelatin levels (normalized to chlorophyll a) in the particulate fraction are similar to those measured in laboratory cultures exposed to picomolar free Cd2+ concentrations and exhibit a decreasing seaward trend. Incubations of natural samples with added Cd2+ confirmed the induction of the peptides by this metal. Ambient phytochelatin concentrations thus appear to provide a measure of the metal stress resulting from the complex mixture of trace metals and chelators in natural waters.

Amino Acid Sequence↗

PubMed1991

Potential effects of UV-B on the chemical environment of marine organisms: a review.

An increase in ultraviolet-B (UV-B) due to depletion of stratospheric ozone may affect growth of marine phytoplankton by altering the chemistry of their environment. Production of bioactive free radicals, photodecomposition of organic matter, and availability of trace metals are likely to be altered by increased UV-B flux. Such changes to the chemical environment may be both deleterious and beneficial to marine phytoplankton. Extracellular free radicals such as OH, Br(2)(-), and CO(3)(-) are predicted to have a negligible impact, but superoxide and its decomposition product hydrogen peroxide may react rapidly with cell surfaces and destroy membrane function and integrity. Increased UV-B will enhance the bioavailability of the redox active trace metals Fe and Cu. Thus, in the Fe-limited high latitude ocean, increased Fe availability may promote phytoplankton production, while in other parts of the ocean increased Cu availability may be toxic. Overall, the interdependent direct and indirect effects of UV-B on phytoplankton may compensate for each other and account for the ability of marine ecosystems to be subjected to widely variable UV-B flux without apparent damage.

Journal Article↗

PubMed1991

Selenocysteyl-tRNA occurs in the diatom Thalassiosira and in the ciliate Tetrahymena.

Selenocysteyl-tRNAs that decode UGA were identified previously in animal and bacterial cells and the genes for these tRNAs have been shown to be widespread in animals and eubacteria. In the present study, we identify a selenocysteyl-tRNA that codes for UGA in Thalassiosira pseudonana, which is a diatom, and in Tetrahymena borealis, which is a ciliate. The fact that these very diverse unicellular organisms also contain a selenocysteyl-tRNA suggests that selenocysteine-containing proteins and the use of UGA as a codon for selenocysteine are widespread, if not ubiquitous, in nature.

Animals↗

PubMed1990

EKG changes in relationship to the chemical peel.

Holter monitor-type EKG studies were done in a series of 10 patients during preoperative baseline and intra- and postoperative periods of Baker-type chemical peel procedures. The intention was to assess the quantitative and qualitative EKG changes occurring before, during, and after the procedures. The results show that there were many spontaneously occurring ectopic beats and changes unrelated to the actual application of the chemical peel formula. Only one of the patients demonstrated such changes, which can be potentially life threatening, occurring in relationship to application of the chemical peel formula.

Aged↗

PubMed1988

Specific Selenium-Containing Macromolecules in the Marine Diatom Thalassiosira pseudonana.

Thalassiosira pseudonana Husedt (Hasle and Heimdal) clone 3H was grown in axenic culture in artificial seawater medium containing 10(-8) molar Na(2) (75)SeO(3). Biochemical distribution of radiolabeled Se was determined by solvent extraction techniques, gel filtration, and polyacrylamide gel electrophoresis. Of the total cellular Se, 51% was protein bound. Two soluble macromolecules of 21 and 29 kilodaltons contained (75)Se. These results are the first to provide evidence of specific Se-containing compounds in a photosynthetic organism. Glutathione peroxidase (GSH-Px) activity was measured in cell-free extracts and on nondenaturing polyacrylamide gels by a glutathione-reductase coupled assay. Two enzymes showing GSH-Px activity were present. One enzyme was active with H(2)O(2) and tert-butyl hydroperoxide (tBOOH); consistent with known Sedependent GSH-Pxs, but the other enzyme was only active with tBOOH. Co-migration of the H(2)O(2)-active GSH-Px and (75)Se on nondenaturing polyacrylamide gels provides evidence that T. pseudonana contains a Sedependent GSH-Px. The molecular weight of one of the (75)Se-labeled macromolecules is identical with the weight of previously characterized GSH-PX subunits. We conclude that the obligate requirement for Se in Thalassiosira pseudonana is due in part to the presence of the selenoenzyme glutathione peroxidase.

Journal Article↗

PubMed1987

Mycosis fungoides: management with topical nitrogen mustard.

The technique of treatment, response rate, freedom from relapse, survival, and complications of therapy in 123 patients treated with topical nitrogen mustard (HN2) for cutaneous mycosis fungoides (MF) at Stanford University Medical Center are reviewed. Patients were treated with HN2 in an aqueous or ointment base with equal efficacy. Response rates depended on the extent of skin involvement. In limited plaque (T1) disease, complete and overall response rates were 51% and 88%, respectively, while in generalized plaque (T2) disease they were 26% and 69%. No patients with tumorous involvement (T3) achieved complete skin clearance and all 13 of these patients developed progression of disease. Only two of nine patients with erythrodema (T4) achieved a complete response (CR), and both later relapsed. After achieving a CR, 40% of patients with T1 disease and 60% with T2 disease later relapsed; however, subsequent therapies, including repeat courses of topical HN2, often were successful in achieving later skin clearance. Overall, 42% of T1 patients and 31% of T2 patients were without evidence of MF at last follow-up. When death occurred, it was usually unrelated to MF in the T1 group. However, half of the deaths of patients with T2 disease were attributable to MF. Among the 22 patients with T3 or T4 disease, 80% of deaths were attributable to MF. The most common complication observed was a cutaneous hypersensitivity reaction, which occurred much more commonly with the aqueous than the ointment preparation. Fourteen patients (11%) developed subsequent cutaneous malignancies.

Adult↗

PubMed1983

Ointment-based mechlorethamine treatment for mycosis fungoides.

The treatment of skin disease with topical mechlorethamine has been restricted because of the frequent development of contact dermatitis. A series of 43 patients with mycosis fungoides in Stages 1A (17), IB (22), II (2), and III (2) were treated with an ointment-based mechlorethamine, prepared by an anhydrous method. Complete clearing occurred in 26 patients over a 42-month evaluation period. The incidence of contact dermatitis was very low. Only 1 of 31 patients exposed to mechlorethamine for the first time, and only 3 of 12 patients with a history of previous hypersensitivity to mechlorethamine, developed contact dermatitis to the ointment-based mechlorethamine.

Administration, Topical↗

PubMed1982

The treatment of mycosis fungoides with ointment-based mechlorethamine.

The use of topical mechlorethamine hydrochloride in the treatment of skin disease has been restricted because of the frequent development of contact dermatitis. A series of 24 patients with mycosis fungoides in stages 1A (eight patients), 1B (15 patients), and 2 (one patient) were treated with ointment-based mechlorethamine, prepared by an anhydrous method. This preparation was therapeutically effective. Complete clearing occurred in 15 of 18 patients with active disease over evaluation periods of up to 27 months, and one patient had partial clearing. Two patients showed a partial relapse during their evaluation periods. The incidence of contact dermatitis was very low: 8% in individuals with a history of hypersensitivity to mechlorethamine and 0% in patients being exposed to the medication for the first time. This new preparation has been shown to be effective therapy for mycosis fungoides. Patient use is associated with minimal side effects.

Administration, Topical↗

PubMed1981

PUVA treatment of erythrodermic and plaque type mycosis fungoides.

Five patients with plaque type mycosis fungoides (MF) and five patients with erythrodermic MF responded favorably to oral psoralen photochemotherapy (PUVA). The mean total UVA irradiation dose was less for erythrodermic than for plaque type MF, but the mean number of treatments to achieve clearing was greater in the erythrodermic patients. Histologic examination at clearing revealed persistence of an inflammatory infiltrate in the lower dermis in most cases. Subsequent recurrent lesions in five patients revealed a more extensive dermal inflammatory infiltrate, although findings were not always diagnostic of MF due to a lack of epidermal involvement. Resumption of more intensive PUVA therapy again resulted in clinical clearing in all five patients. The follow-up period for six patients who received long-term PUVA maintenance ranged from 1 1/2 to 3 1/2 years. During PUVA therapy, five of ten patients developed epithelial malignancies or premalignancies, and one patient developed a malignant fibrous histiocytoma. Most of these patients had received prior treatment with electron beam and topical nitrogen mustard.

Adult↗

PubMed1981

Transdermal scopolamine in the prevention of motion sickness at sea.

Studies were conducted to evaluate the efficacy of scopolamine, absorbed through intact skin, in preventing motion sickness at sea. Efficacy of transdermal scopolamine was compared with oral dimenhydrinate and placebo. Transdermal applications were made 4 to 16 hr before exposure to motion. Dimenhydrinate or placebo was given 1.5 hr before motion and again 2.5 hr after motion began. Comparison with placebo indicated that transdermal scopolamine provided protection against motion sickness at a significance level of p = 0.0001 and oral dimenhydrinate at a level of p = 0.05. Dry mouth, drowsiness, and blurred vision associated with transdermal scopolamine therapy were minimal.

Adolescent↗

PubMed1980

Vitamin C deficiency.

In a case of ascorbic acid deficiency, recognition of the characteristic cutaneous manifestations of this entity is often the first step in making a diagnosis. These features are perifollicular hemorrhages, intrafollicular keratosis and numerous coiled hairs. Treatment of the condition requires a thorough understanding of the precipitating medical and socioeconomic factors of the patient.

Ascorbic Acid Deficiency↗

PubMed1979

Steatocystoma multiplex. Report of a florid case and a review.

A patient had numerous cysts over almost all of his skin surface. The lesions were persistently infected, painful, and odorous, and were contributory to the patient's psychological problems. The cysts were histologically determined to be of the steatocystoma multiplex variety. Several therapeutic modalities were used but only surgical incision, drainage, and electrocautery were beneficial.

Epidermal Cyst↗

PubMed1979

Electron beam therapy. Its effect on eccrine gland function in mycosis fungoides patients.

An observed clinical side effect of total skin surface electron beam therapy is the patient's inability to perspire. An evaluation of eccrine sweat gland function was performed, utilizing acetylcholine chloride and a silicone impression material. The patient's inability to sweat after therapy, and recovery within a three- to six-month period after therapy was demonstrated. This phenomenon should be appreciated by both the physician and the patient prior to electron beam therapy in order to avoid the potential complications of this condition.

Eccrine Glands↗

PubMed1979

Closure of surgical wounds using contiguous island flaps (double V to Y procedure).

Closure of large or cosmetically important surgical wounds is often a difficult problem. The utilization of contiguous island flaps--the double V to Y technique--is evaluated as a primary method of closure. The results obtained with this technique were of high cosmetic quality in all areas of the body in which surgery was performed. Use of the technique avoids tissue distortion, cosmetic defects, grafting, and later reconstructive surgery.

Dermatologic Surgical Procedures↗