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J Griffiths

Publications and source records attributed to J Griffiths.

At least 73 records · Page 4Linked to original sources

Differential sexual activity of isolated and group-housed male mice: influence of acute d-amphetamine sulfate administration.

It is established that group housing can impair sexual activity of male mice, and that central catecholamines are involved in male sexual response, but it is not known whether catecholamine mechanisms are involved in sexual impairment in grouped males. Injections of 0, 0.22, 0.67, 2.0, or 6.0 mg/kg of d-amphetamine sulfate were administered 1 h before testing to individually and group-housed male C57BL/6J mice. Isolated mice showed more mounts, intromissions, and ejaculations and shorter response latencies than did group-housed mice. The latencies to first mount, intromission, and ejaculation were nonmonotonically related to dosage, being shortest at the lowest dosage in isolated mice, but significantly elevated by the higher dosages in both isolated and grouped males. The number of ejaculations was significantly elevated by moderate dosages in both isolated and grouped mice, peaking at the 2.0 mg/kg dosage in isolated mice and at 0.67 mg/kg in grouped mice. Nevertheless, amphetamine treatment generally failed to eliminate differences between males from isolated and grouped backgrounds.

Animals↗

Differential sexual activity of isolated and group-housed male mice: lack of substantial influence of acute or chronic naloxone administration.

Influences of naloxone upon male sexual behavior were examined using two different baseline activity levels: individually and group-housed mice. In Experiment 1, single injections of 0,12.5, or 50 micrograms per animal were administered before testing. Isolated mice showed more sexual activity than did grouped mice; naloxone failed to alter those differences. In Experiment 2, a similar result was obtained despite administration of 50 or 150 micrograms per animal of naloxone. In Experiment 3,0 or 50 micrograms of naloxone was administered to isolated or grouped males daily on the 5 days before testing. Isolated mice showed performance superior to that of grouped mice, but there was no effect of the drug. In Experiment 4, doses of 0. 12.5, or 50 micrograms of naloxone were given to isolated or grouped males twice daily for 7 days prior to testing, producing little effect. These results suggest that the influences of prior social condition on male sexual activity are robust in the face of naloxone administration.

Aggression↗

Photoinactivation of bacteria. Use of a cationic water-soluble zinc phthalocyanine to photoinactivate both gram-negative and gram-positive bacteria.

The photosensitization of microorganisms is potentially useful for sterilization and for the treatment of certain bacterial diseases. Until now, any broad spectrum approach has been inhibited because, although Gram-positive bacteria can be photoinactivated by a range of photosensitizers, Gram-negative bacteria have not usually been susceptible to photosensitized destruction. In the present work, it has been shown that the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, as well as the Gram-positive bacterium Enterococcus seriolicida, can be photoinactivated when illuminated in the presence of a cationic water-soluble zinc pyridinium phthalocyanine (PPC). The degree of photoinactivation is dependent on both the concentration of PPC and the illumination time. In contrast, the three bacteria are not photoinactivated by illumination in the presence of a neutral tetra-diethanolamine phthalocyanine (TDEPC) or negatively charged tetra-sulphonated phthalocyanine (TSPC). Uptake studies have revealed that the lack of activity of TSPC is due to the fact that it has very little affinity for any of the organisms. However, the issue appears to be more complex than simply the gross levels of cellular uptake, since TDEPC and PPC are both taken up by the organisms but only PPC shows activity. This indicates that the localization and subcellular distribution of the phthalocyanines may be a crucial factor in determining their cell killing potential. Further analysis of the uptake data has revealed a cell-bound photosensitizer fraction, which remains tightly associated after several washings, and another weakly bound fraction, which is removed by successive washings. Analysis of the cell killing curves, carried out after successive washings of E. coli exposed to PPC, has revealed that it is the tightly associated fraction that is involved in the photosensitization. Taken together with other data, these results suggest that cationic photosensitizers may have a broader application in the photoinactivation of bacterial cells than the anionic or neutral photosensitizers commonly used in photodynamic therapy.

Dose-Response Relationship, Radiation↗

Variations of lymphocyte subsets associated with stress in depressive populations.

Major depression and dysthymia have been associated with increased perception of day-to-day stressors, greater reliance on emotion-focused coping efforts, and reduced perception of uplifting events. Moreover, it has been observed that levels of circulating natural killer (NK) cells were elevated in depressed patients. Given that mild stressors may increase circulating NK cells, it is conceivable that the elevated NK cells in depression may be secondary to the increased stress perception associated with the illness. In the present investigation a laboratory stressor, comprising a mathematical challenge, increased circulating NK cells; however, the extent of the increase was comparable in depressive, dysthymic and control subjects. Moreover, the increased NK cells induced by the stressor procedure appeared to be independent of variations of plasma cortisol, ACTH or norepinephrine. Interestingly, although the NK changes were not differentially influenced by stressors in the subject populations, in the major depressive patients correspondence existed between NK cell levels and emotion-focused coping styles. Likewise, the response to a laboratory stressor was directly related to the severity of depression and to the use of coping styles involving cognitive restructuring or problem solving.

Adaptation, Psychological↗

Isoforms of alkaline phosphatase determined by isoelectric focusing in patients with chronic liver disorders.

Fractionation of alkaline phosphatase isoenzymes and isoforms by isoelectric focusing is a simple procedure that resolves up to 17 fractions having alkaline phosphatase activity. The fractions are stable at 4 degrees C, and undergo only slight changes during repeated freeze-thaw cycles. Pretreatment with phospholipase-C or sialidase changes the isoelectric focusing patterns of alkaline phosphatase in serum; we recommend they not be used owing to the loss of information. We found that the alkaline phosphatase fractions provide diagnostic information in addition to that given by the common liver-function tests in patients with chronic liver diseases. Primary biliary cirrhosis and primary sclerosing cholangitis showed similar biochemical changes, but they are very different from alcoholic cirrhosis based on the common liver-function tests and the alkaline phosphatase isoform patterns obtained by isoelectric focusing. Analysis of the laboratory data using neural networks has some limited use in distinguishing chronic and chronic-active hepatitis of any cause. We have confirmed the tissue assignments made by Griffiths (Prog Clin Biochem 1989; 8:63-74) for the alkaline phosphatase fractions in liver as obtained by isoelectric focusing: Fractions 1a and 1b show a strong correlation with biliary diseases, and fractions 2, 3, and 4 show consistent increases in patients with primary disorders of hepatocytes; these fractions have good sensitivity for hepatocyte injury, but their specificity is limited. Fraction 10 may be a marker of activated T-lymphocytes; it was abnormal in most of our patients suggesting that it is a sensitive but non-specific test. Analysis of alkaline phosphatase by isoelectric focusing deserves further evaluation, because it may facilitate the diagnosis of certain chronic liver disorders and could be a supplement to the biopsy.

Alkaline Phosphatase↗

Cytomegalovirus colitis mimicking colon carcinoma in an HIV-negative patient with chronic renal failure.

Cytomegalovirus (CMV) colitis is thought to occur almost exclusively in immunosuppressed persons. Colonoscopy in patients with CMV colitis usually shows diffuse or localized ulceration, although mucosal friability, erosions, hemorrhage, and plaque-like pseudomembranes may be observed. We report on a patient with chronic renal failure undergoing hemodialysis therapy who had abdominal symptoms, including bloody diarrhea, along with colonoscopic findings suggestive of carcinoma of the colon. The patient was not infected with the human immunodeficiency virus and had normal lymphocyte subset numbers. He was subsequently found to have invasive CMV disease of the colon. CMV colitis can occur in persons who are not severely immunosuppressed, and its colonoscopic appearance may mimic that of colon cancer.

Carcinoma↗

Growth hormone receptor deficiency (Laron syndrome) in black African siblings.

Non-Caucasians with growth hormone receptor (GHR) deficiency/Laron syndrome among the approximately 180 recognised cases are rare, and include a Japanese and 3 African Americans. Black African siblings, a brother and a sister seen initially at 11 years 9 months and 5 years 6 months of age respectively were -7,4 and -8,0 on the standard deviation score for height. They had characteristic features and biochemical findings including prominent forehead; depressed nasal bridge; central adiposity; high-pitched voices; micropenis; high GH levels and low levels of insulin-like growth factor (IGF)-I, IGF-II, insulin-like growth factor-binding protein 3 (IGFBP-3), and GH-binding protein (the solubilised extracellular domain of the GH cell surface receptor). Molecular genetic studies revealed a dinucleotide deletion in both siblings on exon 7 of the GHR gene, a mutation not found in any other GHR-deficient patient studied, including the North Americans of African origin. Since African Americans have a substantial admixture of Caucasian genes, it is of interest to document the presence of this condition in siblings from Africa.

Adolescent↗

Cryptosporidia--who is at risk?

Cryptosporidium parvum is a coccidian parasite originally described a century ago and, until recently, not considered to be a human pathogen. It has a complex life cycle, including both sexual and asexual reproduction, an auto-infectious cycle, and the ability to complete its development within a single host. The transmission form is a robust, environmentally resistant oocyst, excreted in the stool, which can exist for long periods of time in the environment. Because animals, in particular domesticated livestock, are its primary host, human infection is usually zoonotic. Oocysts often find their way into water supplies, and it resists chlorination and is incompletely filtered from processed drinking water supplies, even when filtration is working optimally. Transmission via ingestion of fecally contaminated swimming pool water, food, fomites, and sexual activities facilitating fecal-oral inoculation have been demonstrated. The major target of C. parvum in the host is the intestinal epithelial cell, resulting in diarrhea, sometimes profuse and persistent, although it may also infect other organs such as the gall bladder and lungs. Pathogenesis involves attachment, probably via a sporozoite lectin, invasion, probably involving apical organelles, replication within a parasitophorous vacuole with the host cell membrane, causing cellular dysfunction. Diagnosis is generally made by visualization of the oocyst form in stool by staining methods, the best of which appears to be auramine and fluorescence microscopy. Those at greatest risk are immunocompromised adults and children, especially those with AIDS, children in day care, travelers to endemic regions, dairy or cattle farm workers of their families or contacts, household contacts of cases or carriers, and possibly owners of infected dogs or cats or their neighbors. There is no specific therapy available, however in the immunocompetent host the illness is self-limited, lasting from a few days to 3 weeks, and long term carriage is uncommon. In the immunocompromised host, infection is prolonged, sometimes asymptomatic, but may result in chronic debilitating diarrhea with dehydration, malabsorption and wasting. Public health measures to reduce contamination of water supplies and vigilant surveillance will reduce the risk to populations. Reducing behaviors favoring fecal-oral transmission, such as certain sexual activities, and scrupulous hygiene in the day care setting would also reduce the likelihood of transmission but not eliminate it. Given our lack of knowledge about Cryptosporidium biology and pathogenesis, high priority should be given to research designed to increase our understanding of the organism and improve the chance of developing useful therapeutic or preventative drugs or strategies.

Adult↗

Stressful life events and coping styles in relation to dysthymia and major depressive disorder: variations associated with alleviation of symptoms following pharmacotherapy.

1. Both major depression and dysthymia (chronic, low grade depression) were associated with increased reports of minor stressors (daily hassles), and feelings of loneliness, reduced uplifts, as well as the use of inappropriate coping strategies (i.e., emotion-focussed rather than problem-oriented coping). 2. Although major depressive and dysthymic patients shared several features with respect to symptomatology, dysthymics tended to report a greater number of hassles than major depressives. 3. Treatment with serotonin reuptake inhibitors over an 8-week period resulted in a marked alleviation of the depressive symptoms in both patient groups, although the clinical effectiveness of the drugs appeared somewhat later in dysthymics. 4. The attenuation of the depressive symptoms was accompanied by a modest, but significant diminution in reports of minor stressors, while the perception of uplifts remained unchanged. Moreover, recovery from depression was associated with changes in coping style, such that patients relied less on inappropriate emotion-focussed coping strategies.

Adaptation, Psychological↗

Interactions of contact, odor cues, and androgens in strange-male-induced early pregnancy disruptions in mice (Mus musculus).

Novel males can disrupt early pregnancy in female house mice (Mus musculus). In Experiment 1, exposure to novel males disrupted pregnancy, but exposure to male urine did not. In Experiment 2, urine from male or female mice or rats painted on females' noses did not influence pregnancy. In Experiment 3, the conjunction of urine painted on female's noses and vulval stimulation did not affect pregnancy more than water with similar stimulation. In Experiment 4, males housed above females were separated from them by a wire mesh grid; intact males disrupted pregnancy, but castrated ones did not. In Experiment 5, such housing of castrated males or ovariectomized females produced a strong disruption of pregnancy if the stimulus animal was given testosterone but not if it was given oil injections. In Experiment 6, transfers of odorous emissions failed to disrupt pregnancy. Contact and androgen activity are necessary for strange males to disrupt pregnancy.

Animals↗

Transient hyperphosphatasemia of infancy and childhood. A study of serum alkaline phosphatase by electrofocusing techniques.

OBJECTIVE: To evaluate serum alkaline phosphatase (ALP) isoenzymes, using a sensitive electrofocusing technique, in transient hyperphosphatasemia of infancy and childhood. DESIGN: Randomized study of infants and children who provided serum samples when an unusual magnitude of total ALP activity was noted. SETTING: Reference enzyme laboratories in Gorizia and Bergamo (Italy) and in Charleston, SC (USA). PATIENTS: A total of 135 infants and children noted to have markedly increased total ALP activity. MAIN OUTCOME MEASURES: Recognition of the disease pathogenesis with appropriate treatment instituted. RESULTS: Three groups of patients were identified: (1) previously healthy patients who showed additional laboratory evidence of viral and protozoal infection, in whom the ALP isoenzyme pattern reflected the primary target organ(s) of the infection; (2) patients with clinical evidence of failure to thrive due to preexisting disease, along with a superimposed infection (the ALP isoenzyme pattern reflected the specific infection and fractions associated with the primary disease); and (3) patients exhibiting failure to thrive (nonorganic or caloric deficit) who did not show evidence of infection. The total ALP in the third group was lower than in the other groups, was of hepatic and bone origin, and decreased when a positive caloric balance was established. CONCLUSION: We examined several mechanisms to explain the hyperphosphatasemia. A perplexing question remains: Will a small group of infants and children respond to infection with this magnitude of ALP activity? Conversely, do all children respond, but a small number fortuitously undergo laboratory measurements that include ALP levels?

Alkaline Phosphatase↗

Central catecholamine alterations induced by stressor exposure: analyses in recombinant inbred strains of mice.

Stressors increase plasma corticosterone concentrations and the turnover of norepinephrine (NE) and dopamine (DA) in some brain regions. However, appreciable interindividual and interstrain differences exist in this respect. The present investigation assessed the NE and DA changes induced by uncontrollable footshock in the BALB/cByJ and C57BL/6ByJ mice and seven recombinant inbred strains. Stressor exposure indeed provoked strain dependent alterations of plasma corticosterone, hypothalamic and mesocortical NE, as well as mesocortcolimbic DA. The profile of stressor effects in the recombinant strains with respect to the NE alterations, the mesocortical DA changes, as well as plasma corticosterone was commensurate with a polygenic mode of inheritance. The data were related to behavioral changes induced by stressors in these strains of mice, as well as to the contribution of the brain amines to stressor-induced behavioral changes.

Animals↗

Norepinephrine and serotonin alterations following chronic stressor exposure: mouse strain differences.

Exposure to acute uncontrollable foot shock influenced the levels and utilization of norepinephrine (NE) and serotonin (5-HT) in several brain regions. These effects varied between the BALB/cByJ and C57BL/6J mouse strains, with the former displaying more pronounced amine variations. Following repeated exposure to foot shock over 15 days, the decline of NE associated with an acute stressor was abrogated. In the hypothalamus, this was accompanied by high MHPG accumulation, suggesting that the increased NE stemmed from a compensatory increase in synthesis. In the locus coeruleus and prefrontal cortex the accumulation of MHPG declined with repeated exposure, possibly suggesting moderation in utilization. In animals exposed to a chronic unpredictable stressor regimen, the NE decline in the hypothalamus was precluded, but pronounced NE reductions were still evident in the locus coeruleus and prefrontal cortex. The data are related to behavioral impairments associated with stressor application, as well as to the particular vulnerability of BALB/cByJ mice to stressor-induced behavioral impairments.

Animals↗

On the photodynamic therapy action spectrum of zinc phthalocyanine tetrasulphonic acid in vivo.

The photodynamic therapy (PDT) activity of zinc phthalocyanine tetrasulphonic acid in a rodent tumour model was shown to be critically dependent on the wavelength of the excitation laser light over a relatively small wavelength range. Thus the sensitizer showed a doubling of the PDT activity with fibrosarcoma LSBD1 in BDIX rats when the wavelength of the illuminant was displaced from 680 to 692 nm. Under these conditions, the sensitizer is approximately three times more effective than polyhaematoporphyrin, whereas previously it has been considered to be of low PDT activity. This wavelength effect is attributed to a red shift of the absorption spectrum of the sensitizer in cells compared with that in solution. Fluorescence excitation studies with sensitizer absorbed in mouse 3T3 fibroblast cells are consistent with such a red shift.

Animals↗