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Biomedical subjects

J A Martin

Publications and source records attributed to J A Martin.

At least 127 records · Page 7Linked to original sources
PubMed1990

Rational design of peptide-based HIV proteinase inhibitors.

A series of peptide derivatives based on the transition-state mimetic concept has been designed that inhibit the proteinase from the human immunodeficiency virus (HIV). The more active compounds inhibit both HIV-1 and HIV-2 proteinases in the nanomolar range with little effect at 10 micromolar against the structurally related human aspartic proteinases. Proteolytic cleavage of the HIV-1 gag polyprotein (p55) to the viral structural protein p24 was inhibited in chronically infected CEM cells. Antiviral activity was observed in the nanomolar range (with one compound active below 10 nanomolar) in three different cell systems, as assessed by p24 antigen and syncytium formation. Cytotoxicity was not detected at 10 and 5 micromolar in C8166 and JM cells, respectively, indicating a high therapeutic index for this new class of HIV proteinase inhibitors.

Amino Acid Sequence↗
PubMed1990

Synthesis and antiviral activity of metabolites of rimantadine.

The hydroxy metabolites of rimantadine (3-5) were synthesized and compared to amantadine (1) and rimantadine (2) for their ability to inhibit the replication of influenza viruses in vitro. All three metabolites were inhibitory to wild-type influenza A viruses (H3N2 and H1N1). In particular, 2-hydroxyrimantadine (3) showed similar activity to amantadine, but the 3- and 4-hydroxy metabolites (4 and 5, respectively), both of which are found in rimantadine-treated patients, showed only modest inhibitory activity. A rimantadine-resistant isolate of influenza A virus exhibited cross-resistance to amantadine and to each of the metabolites 3-5. None of the compounds were effective against influenza B virus.

Adamantane↗
PubMed1990

Synthesis and antiviral activity of monofluoro and difluoro analogues of pyrimidine deoxyribonucleosides against human immunodeficiency virus (HIV-1).

A range of 2'-fluoro and 2',3'-difluoro analogues of pyrimidine deoxyribonucleosides have been synthesized and evaluated against human immunodeficiency virus (HIV-1) in a human lymphoblastoid cell line. Among these compounds, 1-(2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl)cytosine (12), 2',3'-didehydro-2',3'-dideoxy-2'-fluorocytidine (35), 1-(2,3-dideoxy-2,3-difluoro-beta-D-arabinofuranosyl)cytosine (41), and 3'-deoxy-2',3'-didehydro-2'-fluorothymidine (45) were found to have significant antiviral activity, with IC50 values of 0.65, 10, 10, and 100 microM, respectively. The structure-activity relationships are discussed.

Antiviral Agents↗
PubMed1990

Vascular calcium overload produced by administration of vitamin D3 and nicotine in rats. Changes in tissue calcium levels, blood pressure, and pressor responses to electrical stimulation or norepinephrine in vivo.

Increased calcium content of cardiovascular tissues is a phenomenon common to natural aging and various pathological conditions such as hypertension and arteriosclerosis. We investigated an accelerated cardiovascular calcium overload model in young rats produced by treatment with a single dose of vitamin D3 (300,000 IU/kg, i.m.) followed by up to 4 days of twice daily doses of nicotine (25 mg/kg, p.o.). Large increases in the calcium content of the aorta, kidneys, and myocardium but not in the liver or brain were seen. The magnesium content of these tissues was not modified. On the day following the last nicotine injection, there was marked cardiovascular calcium overloading, the aortic calcium level increasing by up to nine times that of controls. The animals had lower body weights, however, and there was a significant degree of mortality (up to 42%). Signs of kidney failure were evident; the blood urea level, for instance, was doubled. If rats were allowed 13 or 180 days to recover, they showed normal growth and kidney function; aortic calcium overload was still pronounced: 16- and 7-fold increases, respectively. Cardiovascular function in recovery animals was characterized by a doubling of pulse pressure. Dose-response curves following noradrenergic stimulation were shifted to the right after 13 (but not after 180) days recovery. Arterial norepinephrine content doubled. The chronic effects of hypervitaminosis D plus nicotine may produce a useful model for the study of the physiological and/or pharmacological consequences of calcium overload.

Aging↗
PubMed1990

Unusual mosaic trisomy 13 through 13/13 translocation and monosomy 13 with a small ring.

Apparently the first patient with de novo mosaicism 46,XX,t(13q13q)/46,XX,-13,+r(13) is described. The two cell lines were present at a frequency of 34% and 66%, respectively. The infant survived for about three months. The prominent dysmorphic features were: birth-weight and head circumference below the 3rd centile, encephalocele, multiple skin tags of low set dysplastic ears, coloboma of the left iris, short upward slanting palpebral fissures, and prominent nasal root. An imperforate anus, recto-vaginal fistula, enlarged adrenals, missing/hypoplastic kidneys, and limb anomalies were also present. It is postulated that the ring is a secondary anomaly arising from the 13q13q translocation.

Abnormalities, Multiple↗
PubMed1989

Synthesis and antiviral activity of phosphonoacetic and phosphonoformic acid esters of 5-bromo-2'-deoxyuridine and related pyrimidine nucleosides and acyclonucleosides.

Phosphonoacetic acid (PAA, 1) was coupled with various acyclonucleosides, 2'-deoxyuridines, cytidines, and arabinosyluracils, with 2,4,6-triisopropylbenzenesulfonyl chloride (TPS) or dicyclohexylcarbodiimide (DCCI) as condensing agents, to give a range of phosphonate esters. The carboxylic ester linkage of PAA to the 5'-position of 5-bromo-2'-deoxyuridine (BUdR, 3) was achieved via the mixed anhydride formed from (diethylphosphono)acetic acid and trifluoroacetic anhydride. Phosphonoformic acid (PFA, 2) was coupled with BUdR by using the DCCI method to give the phosphonate ester. Of these compounds only phosphonate esters in the 2'-deoxyuridine series showed significant activity against herpes simplex virus types 1 and 2. The BUdR-PAA derivative and the BUdR-PFA derivative were highly active, especially the latter, which was more active than the parent nucleoside BUdR against the type 2 virus. The active compounds may exert their effects by extracellular or intracellular hydrolysis to the corresponding antiviral agents, but an intrinsic component of antiviral activity may also be involved.

Antiviral Agents↗
PubMed1988

Intestinal folate absorption in methotrexate treated psoriatic patients.

Thirty-one psoriatic patients 14 of whom were being treated with methotrexate (MTX), participated in a controlled study to evaluate the influence of MTX therapy on the intestinal absorption of folate. Low serum and red cell folate levels in the MTX treated group confirmed previously reported findings. However, analysis of the intestinal absorption profile yielded no significant difference between the two groups. It was concluded that MTX therapy for psoriasis does not adversely affect the intestinal absorption of folate and the observed low body folate status is probably mainly the result of enhanced renal excretion.

Adult↗
PubMed1988

Modification of the ionic environment in the tumor cell by hyperthermia.

Tumor cells submitted to hyperthermia (45 degrees C) showed changes in the ionic composition: Increased calcium and decreased potassium concentrations. These changes are likely to affect vital functions of the cell. The observed decrease in ATP concentration supports the hypothesis that hyperthermia affects the ATP-dependent extrusion mechanism of the cell and, consequently, induces that ionic environment modification. Lactate production was also decreased by hyperthermia, a phenomenon that could be related to the fall in potassium concentration. The intracellular increase in Ca2-concentration during hyperthermia appears to support the earlier hypothesis on the role of Ca2+ in tumor inhibition by hyperthermia.

Animals↗
PubMed1988

In vivo changes of ionic composition of tumors treated by hyperthermia.

Experimental tumors submitted in vivo to hyperthermia, in the presence, or not, of lanthanum (La3+), have shown modifications in the concentration of extra- and intracellular cations. Sacrificed immediately after hyperthermia, only the group treated with La3+ presented ionic changes (lower magnesium and potassium). After 48 hours, in both cases calcium and sodium were increased while magnesium and potassium were decreased.

Animals↗
PubMed1987

The pronunciation of stops in consonant-vowel-consonant (CVC) words: a comparison between normal and speech-disordered preschool children.

A study was made of the pronunciation of stop consonants in CVC words by three groups of preschool children. The two groups of normal children had insignificant problems, but the speech-disordered group had a wide range of errors. Errors in initial position differed from errors in final position. Voicing errors occurred most frequently in initial position, and glottal stop realizations in final position. The incidence of consonant harmony was unexpectedly low, accounting for few errors, and there was no evidence of the "fronting strategy" (Ingram, 1974) in the speech-disordered children.

Child, Preschool↗
PubMed1987

The effects of stress on the psychological well-being of army wives: initial findings from a longitudinal study.

This study examines the relationships between marital and military-specific stress and the general psychological well-being of army wives. These data come from an ongoing three-year longitudinal panel study. Study participants (N = 277) were assessed at two different times 12 to 15 months apart. It was predicted that current marital stress and military life stress would have significant negative (and independent) relationships to well-being, even when prior levels of stress and well-being were taken into consideration. A path model was utilized to analyze the data. These data support the view that both military life stress and marital stress have important independent relationships to the general psychological well-being of army wives. Furthermore, it appears that the relationship between marriage and well-being takes on added importance the longer one stays in the military system.

Adaptation, Psychological↗
PubMed1987

Congenital cytomegalovirus infection: a cause of sensorineural hearing loss.

Prospective studies have suggested that about 108 children with congenital cytomegalovirus (CMV) infection and bilateral sensorineural hearing loss are born each year in England and Wales; this represents about 12% of all children with congenital sensorineural hearing loss. Over a nine year period 1644 children aged between 6 months and 4 years who were attending the Nuffield Hearing and Speech Centre were screened for CMV infection. The prevalence of CMV in the urine of children with sensorineural hearing loss but no immediate family history of deafness was nearly twice that (13%) found in other children with impaired hearing and those with normal hearing (7%). These findings indicate the importance of CMV as a cause of hearing loss.

Child, Preschool↗
PubMed1987

Drug Information Center network: need, effectiveness, and cost justification.

During the past 15 years, the pharmacy profession has experienced much change. Certain pharmacy roles are being challenged and others are coming into existence. Today, health-care practitioners and health-care providers are seeking services not sought before from pharmacists in the area of rational therapeutics. This need for information extends to all pharmacy practice settings: institutional, independent pharmacies, chain stores, governmental agencies, and the pharmaceutical industry. In order to meet this demand for drug and toxicology information, however, the pharmacist must use resources outside the immediate area of his practice. The Drug Information Center (DIC) can be used as such a resource by pharmacists in their daily practice to provide the best possible care with regard to the rational use of drugs for their patients/clients. Specifically, our data indicate that in Tennessee, there is a need for providing drug and toxicology information; pharmacists perceive their role to be providers of drug information as well as drugs; the DIC plays an integral and necessary role as a back-up information resource and in teaching, service, research, and continuing education programs; and the programs provided by the DIC are cost effective and cost justifiable.

Cost-Benefit Analysis↗
PubMed1986

Prognostic factors in choroidal and ciliary body melanomas with extrascleral extension.

In a retrospective study, 50 (8.2%) of 610 patients with malignant melanoma of the ciliary body or choroid had extrascleral extension. Of 46 patients for whom follow-up data were available, 24 (52%) survived five years, 20 (42%) survived ten years, and 17 (37%) survived 15 years. Factors that seemed to affect survival significantly included intraocular tumor size and extraocular tumor size and location. Our observations did not support the role of primary exenteration. Five patients (11%) with extrascleral extension had orbital recurrences and all died within 31 months of surgery regardless of treatment.

Adult↗
PubMed1986

[18F]fluoride from a small cyclotron for the routine synthesis of [18F]2-fluoro-2-deoxy-D-glucose.

[18F]Fluoride was produced via the 18O (p, n) 18F reaction using a low volume stainless steel 18O-water target in a small cyclotron. The average 18F production rate for 60 runs was about 720 microCi/microA-min. A typical bombardment time of 20 min produced 120 mCi of 18F-fluoride. [18F]2-Fluoro-2-deoxy-D-glucose ([18F]2FDG) was prepared using the procedure developed by Tewson [J. Nucl. Med. 24, 718 (1983)] involving a protected cyclic sulfate glucose derivative as precursor. The routine synthesis and quality testing of [18F]2FDG required 1 h and, typically, yields of 30-35 mCi of greater than 95% HPLC-pure product were obtained.

Blood Glucose↗