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Biomedical subjects

J M Clark

Publications and source records attributed to J M Clark.

At least 145 records · Page 8Linked to original sources
PubMed1991

Further observations on the phagocytosis of Candida albicans by hamster and human oocytes.

Pathogenic yeast, Candida albicans, were incubated with hamster and human oocytes for up to 21 hours in order to determine the nature and time course of phagocytosis of these organisms. Aliquotes of the interacting cells were taken at various time intervals for electron microscopic examination. Some specimens had their zona pellucidae enzymatically removed prior to incubation with yeast, and these specimens showed the most extensive interaction and phagocytosis of Candida. The zona pullucida appears to be an effective barrier to yeast, at least over the time span studied. The observations are consistent with the hypothesis of an initial attachment of yeast via a surface component to oocyte microvilli followed by phagocytic uptake into an endosome. There is no compelling evidence of lysosomal degradation of the yeast over the time course of this study; however, the oocytes appear to undergo some degenerative changes at long incubation times.

Animals↗
PubMed1991

A geometric theory of the equilibrium mechanics of fibers in ligaments and tendons.

This paper presents a theoretical analysis of the equilibrium mechanics of bending and twisting fiber geometries in ligaments and tendons. The theory predicts that the bending of loaded fibers is necessarily accompanied by large transverse pressures and pressure gradients. The predicted pressures are especially large at the bone tunnel entries of ligament grafts, where they can equal or exceed the applied tensile loads. Experimental measurements of internal pressures confirm these predictions.

Achilles Tendon↗
PubMed1991

Integrated versus modular theories of number skills and acalculia.

This paper contrasts two views of the cognitive architecture underlying numerical skills and acalculia. According to the abstract-modular theory (e.g., McCloskey, Caramazza, & Basili, 1985), number processing is comprised of independent comprehension, calculation, and production subsystems that communicate via a single type of abstract quantity code. The alternative, specific-integrated theory (e.g., Campbell & Clark, 1988), proposes that visuospatial, verbal, and other modality-specific number codes are associatively connected as an encoding complex and that different facets of number processing generally involve common, rather than independent, processes. The hypothesis of specific number codes is supported by conceptual inadequacies of abstract codes, format-specific phenomena in calculation, the diversity of acalculias and individual differences in number processing, lateralization issues, and the role of format-specific codes in working memory. The integrated, associative view of number processing is supported by the dependence of modular views on abstract codes and other conceptual inadequacies, evidence for integrated associative networks in calculation tasks, acalculia phenomena, shortcomings in modular architectures for number-processing dissociations, close ties between semantic and verbal aspects of numbers, and continuities between number and nonnumber processing. These numerous logical and empirical considerations challenge the abstract-modular theory and support the encoding-complex view that number processing is effected by integrated associative networks of modality-specific number codes.

Humans↗
PubMed1991

Neuroendocrine and behavioural responses to hyperosmolality in rats with lesions of the lateral hypothalamus made by N-methyl-D-aspartate.

Excitotoxic lesions of rat lateral hypothalamus produce impairments in eating and drinking, but not motor deficits. However, it has not been established what causes these eating and drinking impairments. In the present experiments, drinking, plasma osmolality and arginine-vasopressin concentration were measured in lateral hypothalamic-lesioned and control rats following systemic injection of hypertonic saline. In response to hyperosmolality, N-methyl-D-aspartate-lesioned rats drank significantly less than controls but showed normal increases in plasma osmolality and arginine-vasopressin concentration. This dissociation of neuroendocrine and behavioural responses suggests that the impairment of rats with excitotoxic lesions of the lateral hypothalamus is unrelated to physiological (as opposed to behavioural) mechanisms of homeostasis.

Animals↗
PubMed1991

The regulation of feeding and drinking in rats with lesions of the lateral hypothalamus made by N-methyl-D-aspartate.

Rats bearing excitotoxic lesions of the lateral hypothalamus are hypodipsic and hypophagic, but responses to 24 h food or water deprivation are normal, as are responses to different taste stimuli. The most striking deficit present in lateral hypothalamic-lesioned rats is an inability to respond as controls to dehydrating, dipsogenic or glucoprivic challenges. The present experiments examined the ability of rats bearing bilateral N-methyl-D-aspartate-induced lesions of the lateral hypothalamus to recognize and respond to changes in their internal environments. All of the lesioned rats tested showed mild to moderate hypophagia and hypodipsia, and none responded properly by drinking over 1 h after i.p. injection of hypertonic saline. However, the addition of glucose to the water supply promoted an increase in drinking and a decrease in lab chow consumption to maintain a constant energy intake; the addition of salt to the diet promoted an increase in drinking and no change in eating; 24 h water deprivation induced the same amount of drinking in lateral hypothalamic-lesioned rats as in controls; and injection i.p. of water (but not physiological saline) before drinking water was returned to rats which were 24 h water deprived suppressed drinking. These data suggest that lateral hypothalamic-lesioned rats are in receipt of normal information from their peripheries, and that they can adjust their behaviour over a period of days or minutes to changes in the internal milieu. The most consistent deficit is in responding actively and rapidly to challenging stimuli; the nature of this and the mechanisms which might produce it are discussed. We suggest that the consequences of excitotoxic lesion are better explained by disruption of input to the cortex from the lateral hypothalamus rather than by interference with metabolic processes.

Adaptation, Physiological↗
PubMed1991

Synthesis and antiviral activity of enantiomeric forms of cyclobutyl nucleoside analogues.

The syntheses of the enantiomeric cyclobutyl guanine nucleoside analogues [1R-1 alpha, 2 beta, 3 alpha]- and [1S-1 alpha, 2 beta, 3 alpha]-2- amino-9-[2,3-bis(hydroxymethyl)cyclobutyl]-6H-purin-6-one (7 and 8, respectively) and the enantiomeric cyclobutyl adenine analogues [1R-1 alpha, 2 beta, 3 alpha]- and [1S-1 alpha, 2 beta, 3 alpha]-6-amino-9-[2,3-bis(hydroxymethyl) cyclobutyl]purine (9 and 10, respectively) are described. trans-3,3-Diethoxy-1,2-cyclobutanedicarboxylic acid (14) was coupled with R-(-)-2-phenylglycinol to provide a mixture of diastereomeric bis-amides, 15a and 15b, which was readily separated by crystallization. Conversion of each bis-amide to the corresponding diol enantiomer, 16a and 16b, respectively, was effected by a facile three-step sequence in high overall yield. Homochiral diol 16a was converted in a straightforward manner to 7 and 9, and homochiral diol 16b was similarly converted to the corresponding optical isomers 8 and 10. Compounds 7 and 9, which mimic the absolute configuration of natural nucleosides, are highly active against a range of herpesviruses in vitro while the isomers of opposite configuration, 8 and 10, are devoid of antiherpes activity. The corresponding triphosphates of 7 and 8 (7-TP and 8-TP) were prepared enzymatically. Compound 7-TP selectively inhibits HSV-1 DNA polymerase, compared to human (HeLa) DNA polymerase, while 8-TP is much less inhibitory than 7-TP against both types of enzymes. Compounds 7 and 9 are efficacious in a mouse cytomegalovirus model infection.

Animals↗
PubMed1991

Unexpected sequence diversity in the amino-terminal ends of the coat proteins of strains of sugarcane mosaic virus.

The sequence of the 3'-terminal 1343 nucleotides of the SC strain of the sugarcane mosaic virus (SCMV-SC) genome was compared with the 1376 nucleotides at the 3' terminus of maize dwarf mosaic virus B (MDMV-B). The SCMV-SC sequence includes an open reading frame which codes for the viral coat protein of 313 amino acids (nucleotides 157 to 1116), followed by a 3' non-coding region of 235 nucleotides and a poly(A) tail. The MDMV-B sequence codes for the capsid protein (nucleotides 157 to 1139) of 328 amino acids and has a 3' non-coding region of 236 nucleotides. The coat protein of SCMV-SC has 92% identity with that of MDMV-B except for the region between amino acid residues 27 and 70 of SCMV-SC. This region of SCMV-SC is smaller (44 residues) than the equivalent region in MDMV-B (59 residues) and has only 22% identity with the MDMV-B sequence. Possible mechanisms for the generation of this sequence diversity are discussed. Despite this diversity, the sequence identities of both the major part of the coat proteins and the 3' non-coding regions confirm the proposal, based on previously described serological data, that SCMV-SC and MDMV-B are strains of SCMV.

Amino Acid Sequence↗
PubMed1991

Tissue distribution of amphotericin B lipid complex in laboratory animals.

Amphotericin B lipid complex (ABLC), under development for the treatment of serious fungal disease, is not a true liposome but a complex of amphotericin B, dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol with a particle size range of 1.6-6.0 microns. Tissue distribution of ABLC was determined in mice and rats after i.v. or i.p. administration. ABLC resembles typical liposomal preparations with amphotericin B concentrating in the reticuloendothelial system. After a single i.v. treatment with ABLC, amphotericin B was present in high concentrations in liver, lung and spleen of mice and rats while plasma levels were consistently low. Mouse liver contained 48% of the administered dose 1 h after treatment and always contained the largest amount of amphotericin B after ABLC treatment. In mice treated once daily for 7 consecutive days with 10 mg kg-1 ABLC, liver amphotericin B concentration reached 377 micrograms g-1. Tissue concentrations of amphotericin B were substantially lower when ABLC was given i.p. instead of i.v. with reticuloendothelial tissues containing 2- to 7-fold more after i.v. treatment. Animals treated with 10 mg kg-1 ABLC for 14 consecutive days showed no overt signs of toxicity and had only transient changes in liver and kidney function after treatment.

Amphotericin B↗
PubMed1991

Amphotericin B lipid complex therapy of experimental fungal infections in mice.

The amphotericin B lipid complex (ABLC), which is composed of amphotericin B and the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, was evaluated for its acute toxicity in mice and for its efficacy in mice infected with a variety of fungal pathogens. ABLC was markedly less toxic to mice when it was administered intravenously; it had a 50% lethal dose of greater than 40 mg/kg compared with a 50% lethal dose of 3 mg/kg for Fungizone, the desoxycholate form of amphotericin B. ABLC was efficacious against systemic infections in mice caused by Candida albicans, Candida species other than C. albicans, Cryptococcus neoformans, and Histoplasma capsulatum. ABLC was also efficacious in immunocompromised animals infected with C. albicans, Aspergillus fumigatus, and H. capsulatum. Against some infections, the efficacy of ABLC was comparable to that of Fungizone, while against other infections Fungizone was two- to fourfold more effective than ABLC. Against several infections. Fungizone could not be given at therapeutic levels because of intravenous toxicity. ABLC, with its reduced toxicity, could be administered at drug levels capable of giving a therapeutic response. ABLC should be of value in the treatment of severe fungal infections in humans.

Amphotericin B↗
PubMed1991

Evaluation of SQ 34,514: pharmacokinetics and efficacy in experimental herpesvirus infections in mice.

The new antiviral nucleoside SQ 34,514 [(1R-1 alpha, 2 beta, 3 alpha)-2-amino-9- [2,3-bis(hydroxymethyl)cyclobutyl]-6H-purin-6-one], the active R isomer of racemic SQ 33,054 (cyclobut-G), was evaluated for efficacy in the treatment of herpesvirus infections in mice. SQ 34,514 was orally efficacious in a herpes simplex virus type 1 (HSV-1) systemic infection, an intracerebral HSV-2 infection, a vaginally induced HSV-2 infection in ovariectomized mice, and in a systemic murine cytomegalovirus infection. SQ 34,514 compared favorably with acyclovir and ganciclovir in the treatment of these experimental infections. In mice, SQ 34,514 had an oral bioavailability of 80% based on urinary excretion. SQ 34,514 may have potential value in the therapy of HSV and cytomegalovirus infections in humans.

Animals↗
PubMed1991

Pulmonary function in men after oxygen breathing at 3.0 ATA for 3.5 h.

As a pulmonary component of Predictive Studies V, designed to determine O2 tolerance of multiple organs and systems in humans at 3.0-1.5 ATA, pulmonary function was evaluated at 1.0 ATA in 13 healthy men before and after O2 exposure at 3.0 ATA for 3.5 h. Measurements included flow-volume loops, spirometry, and airway resistance (Raw) (n = 12); CO diffusing capacity (n = 11); closing volumes (n = 6); and air vs. HeO2 forced vital capacity maneuvers (n = 5). Chest discomfort, cough, and dyspnea were experienced during exposure in mild degree by most subjects. Mean forced expiratory volume in 1 s (FEV1) and forced expiratory flow at 25-75% of vital capacity (FEF25-75) were significantly reduced postexposure by 5.9 and 11.8%, respectively, whereas forced vital capacity was not significantly changed. The average difference in maximum midexpiratory flow rates at 50% vital capacity on air and HeO2 was significantly reduced postexposure by 18%. Raw and CO diffusing capacity were not changed postexposure. The relatively large change in FEF25-75 compared with FEV1, the reduction in density dependence of flow, and the normal Raw postexposure are all consistent with flow limitation in peripheral airways as a major cause of the observed reduction in expiratory flow. Postexposure pulmonary function changes in one subject who convulsed at 3.0 h of exposure are compared with corresponding average changes in 12 subjects who did not convulse.

Adult↗
PubMed1991

Nontraumatic femur fracture in an oligomenorrheic athlete.

Exercise-associated amenorrhea is the cessation of menses in a woman following onset of training or an increase in training intensity. Its physiologic basis is characterized by consistently low levels of gonadotropin and ovarian hormones, but the underlying cause of this phenomenon is unknown. Although osteopenia has been described in amenorrheic women athletes, it has been primarily a laboratory diagnosis. Several recent studies have described a significantly lower bone mineral density (BMD) in the lumbar spine of amenorrheic athletes. Marcus et al. also reported an increased number of metatarsal and tibial stress fractures in a group of amenorrheic women. We report here the first case of a nontraumatic femur fracture in an amenorrheic athlete. A 32-yr-old white female, with four prior fibular stress fractures, suffered a left femoral shaft fracture during the 13th mile of a half-marathon. The fracture was successfully internally fixed. Biochemical studies showed no metabolic abnormality. Bone mineral density of the lumbar spine, femoral neck, tibia, and fibula were below the mean for both eumenorrheic and amenorrheic female athletes. Exercise-associated amenorrhea is a medical problem that may have serious implications for both competitive and high-intensity recreational female athletes.

Adult↗
PubMed1990

The interrelation of fiber bundles in the anterior cruciate ligament.

The anterior cruciate ligaments (ACL) of dogs, humans, and rabbits were studied by light and scanning electron microscopy after fixation in situ. In all species, the ACL was composed of multiple 20 microns-wide collagen fiber bundles separated by columns of cells in fibrous capsules. These bundles were in turn grouped into fascicles of varied size. The fascicles were surrounded by thin membranous sheets that ran through the ligament forming single or multiple layers between fascicles. Splaying of the ACL at insertion was created by increased volume in the cellular intervals. Bending of the fiber bundles occurred in this region--which corresponds to the fibrocartilaginous zone. We propose that the cell layers accommodate compressive forces and the membranes allow slipping among fascicles without compromising blood supply.

Aged↗
PubMed1990

Observations of hamster sperm-egg fusion in freeze-fracture replicas including the use of filipin as a sterol marker.

We have extended the observations of previous transmission electron microscopy studies of sperm-egg fusion to include those of freeze-fracture replicas showing sperm-egg interactions before, during, and following sperm head fusion with the egg membrane. Hamster eggs were incubated with hamster sperm under polyspermic conditions and were observed after a period of 5-30 minutes. After fixation, the eggs and sperm were exposed to filipin, which binds beta-OH-sterols to form visible complexes in freeze-fracture replicas. Filipin can act as a marker for egg plasma membrane wherein it is abundant, while filipin is relatively scarce in the acrosome-reacted hamster sperm membrane, found only in the plasma membrane of the equatorial segment. The earliest sperm-egg interactions are observed between the egg microvilli and the perforatorium and the equatorial segment of the sperm, and the initial fusion between egg and sperm occurs in the vicinity of the equatorial segment. At later stages of fusion involving the postacrosomal segment, a clear line of demarcation is observed between the filipin-rich egg membrane and the filipin-poor sperm postacrosomal segment, suggesting that filipin binding lipids from the egg intercalate into the sperm membrane following membrane fusion. The anterior segment of the sperm does not fuse with the egg but is instead incorporated into a cytoplasmic vesicle derived from both sperm and egg membranes. In this latter step, filipin-sterol complexes are not found in sperm-derived membranes suggesting that there may be barriers to the movement of filipin binding lipids from the egg into these sperm membranes.

Animals↗
PubMed1990

(+-)-(1 alpha,2 beta,3 alpha)-9-[2,3-bis(hydroxymethyl)-cyclobutyl] guanine [(+-)-BHCG or SQ 33,054]: a potent and selective inhibitor of herpesviruses.

(+-)-(1 alpha,2 beta,3 alpha)-9-[2,3-bis(hydroxymethyl)cyclobutyl] guanine [(+-)-BHCG or SQ 33,054] is a newly synthesized nucleoside analog with potent and selective antiviral activity against members of the herpesvirus group, including human cytomegalovirus. The activity against a thymidine kinase deficient HSV-2 mutant was 25-fold poorer than against the parent virus, suggesting that phosphorylation is an important prerequisite for antiviral activity against HSV-2. (+-)-BHCG is readily phosphorylated by purified HSV-1 thymidine kinase, and BHCG triphosphate synthesized enzymatically is a selective inhibitor of HSV-1 DNA polymerase. (+-)-BHCG did not inhibit host cell growth at concentrations at least 1000-fold higher than HSV-2 inhibitory concentrations. Subcutaneous administration of (+-)-BHCG was protective against HSV-1 systemic infections in mice. BHCG is an exciting antiviral agent and represents a new class of nucleoside analogs.

Acyclovir↗
PubMed1990

Fish consumption advisories: toward a unified, scientifically credible approach.

A model is proposed for fish consumption advisories based on consensus-derived risk assessment values for common contaminants in fish and the latest risk assessment methods. The model accounts in part for the expected toxicity to mixtures of chemicals, the underlying uncertainties in the health and exposure data, and the amount of contaminated fish consumed. Application of the model to a larger number of chemicals is possible. Noncancer toxicity is used as an example, but this model is applicable for risks from cancer as well. A second related model is proposed that is useful for comparing potential risks among sites (e.g., rivers and lakes).

Animals↗
PubMed1990

Helping people to stop smoking: a study of the nurse's role.

Sixteen trained nurses from various clinical backgrounds participated in a project designed to describe the process and assess the outcome of their attempts to help a range of patients and clients to stop smoking. A case-study approach was employed and the nurses initiated 68 health education interventions related to smoking cessation. All interventions were tape-recorded and data on patients' and clients' characteristics, smoking history, health beliefs and motivation to give up smoking were also collected. Forty-two patients were followed up 1 year post-intervention. Data collected at this time revealed that 17% had successfully given up smoking, while a further 12% had substantially reduced their cigarette consumption. These findings compare very favourably with those of previous studies in which general practitioners have attempted to help patients stop smoking. The results of the research reported here therefore suggest that nurses have enormous potential for fulfilling a highly effective health education function.

Attitude to Health↗