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Biomedical subjects

R K Martin

Publications and source records attributed to R K Martin.

17 recordsLinked to original sources
PubMed1992

Fluoxetine hydrochloride enhances in vitro susceptibility to chloroquine in resistant Plasmodium falciparum.

The emergence of chloroquine resistance in Plasmodium falciparum has necessitated the development of alternate strategies for chemotherapy and chemoprophylaxis. One approach has been the identification of drugs that do not possess any intrinsic antimalarial activity when used alone but that potentiate the effect of currently available antimalarial drugs, such as chloroquine. We identified fluoxetine hydrochloride (Prozac), a commonly prescribed antidepressant, as another resistance modulator for drug-resistant P. falciparum. Studies with chloroquine-resistant clones and isolates from various geographical locations confirmed our initial observations with a chloroquine-resistant P. falciparum clone, W2. Fluoxetine concentrations of 500 nM were found to effectively modulate chloroquine resistance by 66% in clone W2. In comparison, verapamil at similar concentrations was observed to modulate chloroquine resistance in clone W2 by 61%. Neither fluoxetine nor verapamil was observed to possess any innate antimalarial activity. These data augment the current description of the chloroquine resistance phenotype and may provide additional insights into lead-directed synthesis of new antimalarial drugs.

Animals↗
PubMed1991

Structural diversity in the Plasmodium falciparum merozoite surface antigen 2.

Antigens associated with the surface of merozoites of the malaria parasite Plasmodium falciparum are directly accessible to immune attack and therefore are prime vaccine candidates. We have previously shown that one of the two known merozoite surface antigens (merozoite surface antigen 2; MSA-2) exhibits considerable sequence and antigenic diversity in different isolates. The sequences of MSA-2 from three isolates revealed a central domain composed of repeats that vary in number, length, and sequence, flanked in turn by nonrepetitive variable sequences and by conserved N- and C-terminal domains. We report here the sequences of a further four MSA-2 alleles, containing repetitive sequences that are related but not identical to each other. The seven alleles of MSA-2 can be divided into two distinct allele families on the basis of nonrepetitive sequences. Hybridization studies with repeat probes indicated that all of the 44 P. falciparum isolates examined contained repeat regions similar to those defined in known MSA-2 sequences.

Amino Acid Sequence↗
PubMed1991

Characterization of a Leishmania isolate from the rodent host Neotoma micropus collected in Texas and comparison with human isolates.

We report the biological and biochemical parameters of Leishmania parasites (MNEO/US/90/WR972) isolated from a rodent host, Neotoma micropus, collected in Texas. Footpad inoculations of WR972 promastigotes into BALB/c mice and Syrian hamsters resulted in ulcerating lesions six and eight weeks post-inoculation, respectively. Using monoclonal antibody-stained touch preparations, amastigotes were found in the liver of both laboratory hosts. Infection of J774 macrophages with WR972 promastigotes supported the growth of amastigotes for 12 days at 35 degrees C. The WR972 parasite was identified by enzyme electrophoresis as L. mexicana. Isozyme comparison of WR972 with 42 L. mexicana isolates (from humans and rodents) from four different endemic areas, including Texas, suggest that these parasite populations are identical for approximately 97% of their genetic loci. Pulse field gel electrophoresis (PFGE) of WR972 resolved 18 chromosomes with a size range of 300- greater than 2,000 kb. The karyotype strongly resembles that of two other Texas L. mexicana isolates from humans. Taken together, the PFGE, hybridization, and isoenzyme data suggest that the wood rat isolate (WR972) is identical to parasites from human cutaneous lesions isolated in Texas and Central America. In addition, the biological characteristics of WR972, its infectivity of BALB/c mice and the Syrian hamster, and the potential of the isolate to infect, transform, and divide in J774 macrophages indicate that WR972 will be pathogenic in humans if transmission occurs. Health care providers should consider this possibility when studying the epidemiology and control of cutaneous leishmaniasis in Texas.

Animals↗
PubMed1991

Characteristics of multidrug resistance in Plasmodium and Leishmania: detection of P-glycoprotein-like components.

Multidrug-resistance (MDR) in neoplastic cells is frequently characterized by the overexpression of P-glycoprotein (PGP), a 170 kDa transmembrane glycoprotein that binds multiple cytotoxic drugs as well as calcium channel antagonists. Chloroquine resistance in Plasmodium falciparum appears to be analogous to MDR in neoplastic cells, where the induction of resistance with one drug confers resistance to other structurally and functionally unrelated drugs. To test the hypothesis that chloroquine resistance in P. falciparum and antimony resistance in Leishmania is mediated by a similar mechanism of MDR in mammalian neoplastic cells, a PGP-specific monoclonal antibody (C219) was used to determine the presence of PGP genes in resistant and sensitive Plasmodium and Leishmania parasites by indirect immunofluorescence assays and Western blotting procedures. These PGP-like components were detected in both drug-sensitive and -resistant Plasmodium and Leishmania cells. A 40-42 kDa component was observed to be greater in a chloroquine-resistant P. berghei (C line) than in a chloroquine-susceptible P line. Differences observed between Pentostam-resistant and -sensitive Leishmania promastigote clones and isolates included the increased expression of 96-106 and 23-25 kDa peptides in drug-resistant L. enrietti, and increased amounts of two different peptides in two drug-resistant L. panamensis clones (i.e., 96-106 and 43-45 kDa in WR-746-CL4, and 53 and 23-25 kDa in kDa) in amastigotes as in MDR KB carcinoma cells (KB-V1). Comparative indirect immunofluorescent studies suggested that a correlation existed between the degree of antimony susceptibility and the concentration of the moiety recognized by C219 in two L. panamensis clones. Binding of the C219 monoclonal antibody to the PGP-like component of Leishmania was blocked by Pentostam, while the binding of C219 to multiple-drug resistant KB-V1 PGP was not inhibited by Pentostam, regardless of the PGP concentration. This suggests some degree of specificity in the binding of Pentostam to the Leishmania PGP-like components. In addition, these studies have demonstrated that drug-sensitive Leishmania accumulate two to five times more 125Sb-Pentostam than resistant clones.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum.

The lethal form of human malaria caused by Plasmodium falciparum is virtually uncontrollable in many areas because of the development of drug resistance, in particular chloroquine resistance (CQR). CQR is biologically similar to the multiple drug resistance phenotype (MDR) of mammalian tumour cells, as both involve expulsion of drug from the cell and both can be reversed by calcium channel antagonists. A homologue (pfmdr1) of the mammalian multidrug resistance gene has been implicated in CQR because it is amplified in some CQR isolates of P. falciparum as is an mdr gene in MDR tumour cells. We show here that the complete sequences of pfmdr1 genes from 2 CQ sensitive (CQS) P. falciparum isolates are identical. In 5 CQR isolates, 1-4 key nucleotide differences resulted in amino acid substitutions. On the basis of these substitutions, we have correctly predicted the CQS/CQR status of a further 34 out of 36 isolates. This is a paradox as CQR arises much less frequently than would be predicted if single point mutations were sufficient. We conclude that a mutated pfmdr1 gene is one of at least two mutated genes required for CQR.

Alleles↗
PubMed1988

Cystic fibrosis DNA markers in Alabama blacks.

DNA samples from unrelated Alabama blacks with no family history of cystic fibrosis (CF) were analyzed with DNA markers linked to cf. Allelic frequencies of genetic markers detected by probes pmetH, pmetD, XV2c, KM19, and pJ3.11 were compared to those of other populations. Allelic frequencies for pJ3.11, XV2c, and KM19 in Alabama blacks and previously studied Caucasian populations were similar. In contrast, the met locus allelic frequencies in Alabama blacks were markedly different from those in Caucasian populations.

Alabama↗
PubMed1988

Distribution and deposition of tritiated cortisol using phonophoresis.

Tritiated cortisol cream was coupled with light-microscopic autoradiography to histologically trace the distribution and deposition of a topical application of cortisol driven in by a therapeutic dose of ultrasound. Fifteen dogs were divided into four distinct groups: Group 1 consisted of two control dogs; Group 2, four dogs that received 10% radioactive cortisol and no ultrasound; Group 3, four dogs that received 5% radioactive cortisol plus ultrasound; and Group 4, five dogs that received 10% radioactive cortisol plus ultrasound. Although the cortisol applied to all dogs was limited to the epidermis, penetration occurred beyond the stratum corneum. The combination of 10% cortisol and ultrasound showed more penetration than 10% cortisol alone (p = .018), suggesting that ultrasound may be useful in the transdermal delivery of cortisol cream. The difference between the penetration of 5% and 10% cortisol when treated with ultrasound was only marginally significant (p = .062).

Administration, Topical↗
PubMed1985

Cross-sectional thigh components: computerized tomographic assessment.

The purpose of this study was to examine the efficacy of the Picker Synerview Fourth Generation CT Scanner in assessing cross-sectional areas of muscle, bone, and subcutaneous fat of the thigh. A secondary purpose was to resolve individual muscle bellies using the CT scanner and to determine the effects of body composition in isolating those muscles. Both limbs of one cadaver were used to compare actual cross-sectional areas with the CT images. Each limb was dissected and photographed. Accuracy of repeated measurements was assessed using human volunteers. Absolute and percent error between the CT measurements and the measurements of the cross-sectional areas differed most at the bone. No differences were found between repeat scans. CT images and photographic measurements of individual muscles were generally quite similar, as assessed by absolute and percent error. The gracilis and sartorious were reasonably well defined in those individuals with more than 8% body fat. The results are discussed in terms of possible applications of the CT scanner in sports medicine research.

Adipose Tissue↗
PubMed1979

Concurrent exercise of dogs using carousel-type treadmill.

To exercise several animals at the same time, a carousel-type treadmill was constructed. Horizontal extensions secured to a motorized central shaft allow six dogs to be run concurrently. To counter the effect of centrifugal force, a rubberized banked running track was built. The track was also designed so that it can be hosed down for easy maintenance. During the past 2 yr, the treadmill has not required any maintenance, and only minimal attention has been necessary on the track.

Animals↗
PubMed1978

Influence of age and sex on the strength of bone-ligament junctions in knee joints of rats.

The bone-ligament junction strength of femur-medial collateral ligament-tibia complexes in rats was measured in situ at various ages during a two-year period. Male rats had a higher junction strength than female rats, a difference that became apparent when the animals were sixty days old and in male but not female animals subsequently paralleled the changes in body weight. However, on a bodyweight basis, the junctions were stronger in female than in male rats and this sex difference was evident at fifteen days old and persisted thereafter. Regression analysis between body weight and junction strength indicated that female rats had a significantly higher slope than males, which suggested that the sex differences were due to a hormonal factor or factors. Other measurements showed that elastic stiffness, failure energy, and collagen concentration in the ligament increased, whereas the water content of the ligament decreased with age. Most of these changes could be attriubted to the aging process and not the sex of the animal. It was concluded, however, that the strength of the insertion sites of ligaments on bones are responsive to the hormonal fluctuations that occur with aging.

Age Factors↗
PubMedDate not supplied

Innate resistance to new antimalarial drugs in Plasmodium falciparum from Nigeria.

The rapid dissemination of chloroquine-resistant Plasmodium falciparum in West Africa has been well documented and represents a significant health threat to autochthonous populations. The methodical development of alternative chemotherapeutic agents demands that dispensing new antimalarial drugs (mefloquine, halofantrine, and artemisinine [qinghaosu]) be closely monitored in order to protect their clinical utility. Indeed, mefloquine-resistant strains of P. falciparum have been reported. We present data from experiments in vitro on the innate resistance of P. falciparum isolates to mefloquine as well as a disturbing observation of transient resistance to artemisinine. The implications for the extended efficacy of these new antimalarial drugs are addressed.

Animals↗
PubMedDate not supplied

Head and neck injuries in college football: an eight-year analysis.

The present study documented head and neck injuries in a study group of 342 college football players at a single institution for a period of 8 years. All freshmen players were screened for evidence of: (1) past history of head and neck injuries, and (2) abnormalities of the cervical spine on physical examination and x-ray film. By recording all head injuries and those neck injuries with time loss, incidence rates and patterns of injury incurred in college competition were determined. A total of 175 head and neck injuries were sustained by 100 players over the 8 year period. Those players with abnormal findings on screening examination were twice as likely to have a head or neck injury at some point in their college careers as those players with a normal screening examination. The greater the degree of abnormality on freshman screening examination, the more severe the neck injury in college was likely to be. Twenty-nine percent of all players in the study group sustained a head or neck injury during their college careers. The probability of a subsequent head or neck injury escalated sharply following a single incident. The overall incidence of injury was found to have been dramatically reduced over the 8 years. Influential factors such as legislative rule changes, medical status of recruits, and general coaching philosophies are discussed with regard to injury reduction and prevention of head and neck injuries in college football.

Adult↗
PubMedDate not supplied

Sports injuries at the 1985 Junior Olympics. An epidemiologic analysis.

The XIX Junior Olympic Games, hosted in Iowa City, Iowa, in August of 1985, involved 3,028 athletes who participated for 7 days in 13 different sports at 8 separate sites. Medical coverage for the Games was provided by the University of Iowa Sports Medicine Service. Staffing for the events involved approximately 75 physicians, 60 athletic trainers, and other health care personnel. A triage protocol was established prior to the Games whereby the athletic trainer would make first contact with the injured athlete and would evaluate and treat the injury based on standing orders. If in the judgment of the trainer, the athlete needed to be referred to a physician, one would be available, either on site or on call. During the Games, 1,113 medical encounters were recorded, 121 of those being deemed serious enough to withhold an athlete from competition pending further evaluation and treatment. The 121 significant injuries and illnesses involved 116 athletes (66% male, 34% female). Thirty-four percent of the significant injuries only required treatment by the trainer, while 46% were referred to an on site physician and 20% needed a specialty consultant. Seventeen percent of the significant injuries resulted in the athlete being medically disqualified for the remainder of the event. The most common injuries/illnesses were contusions (26%), sprains (21%), heat (17%), strains (9%), and other illnesses (12%). According to body region, 44% of the 121 injuries were to the lower extremity, 26% to the head, neck, and trunk, and 12% to the upper extremity.(ABSTRACT TRUNCATED AT 250 WORDS)

Athletic Injuries↗