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Biomedical subjects

C Lee

Publications and source records attributed to C Lee.

At least 613 records · Page 34Linked to original sources

Growth of the rat prostate gland is facilitated by the autonomic nervous system.

Many factors are implicated in the development of prostatic growth: androgens, growth factors, and stromo-epithelial interaction. This study examines the role of the sympathetic and parasympathetic branches of the autonomic nervous system control of different aspects of rat prostate growth and atrophy. Unilateral sympathectomy leads to decreases in ventral prostate weight, DNA, and protein content in the lesioned side. Unilateral parasympathectomy leads to increases in ventral prostate weight, DNA, and protein content in the intact side. The separate effects of sympathectomy and parasympathectomy are maintained across a diverse combination of neural manipulations. Significant re-innervation does not occur by 60 days after manipulation as assessed by tissue norepinephrine levels. There appears to be a differential effect of the autonomic nervous system on growth and maintenance of the ventral prostate. The mechanism of contralateral hyperplasia and ipsilateral atrophy has potential significance in understanding human abnormal prostate growth.

Animals↗

Ibuprofen treatment of ischemic musculocutaneous flaps.

The nonsteroidal antiinflammatory drug ibuprofen was tested as a potential agent in the pharmacological management of ischemia and reperfusion injury of swine flaps. After 6 hours of global ischemia, ibuprofen treatment was found to significantly improve the postischemic musculocutaneous flap survival. This was demonstrated by a dramatic 30.4 +/- 9.3% (p < or = 0.005) improvement in ischemic muscle survival, whereas the skin survival of ischemic musculocutaneous flaps was only moderately improved by 6.0 +/- 3.2% (p < or = 0.05). Thus, ibuprofen is potentially a powerful and effective treatment agent in the management of critically ischemic flaps and replants with high skeletal muscle content.

Animals↗

The progression of HCV-associated liver disease in a cohort of haemophilic patients.

We have studied morbidity and mortality related to hepatitis C virus infection in haemophilic patients treated at our centre. 11/255 HCV seropositive patients have developed hepatic decompensation. 20 years after first exposure to lyophilized clotting factor concentrate the risk of hepatic decompensation is estimated to be 10.8% (95% CI 3.8-17.8%). There is a significantly increased risk associated with HIV infection, and also with increased age. For HIV seropositive patients the rates of decline in CD4 lymphocyte count and the development of p24 antigenaemia are significant risk factors for hepatic decompensation. Cirrhosis was seen in 9/19 HIV seropositive patients at post mortem. There was an association of cirrhosis with increased age but not with CD4 count, p24 antigenaemia, or AIDS. In conclusion, HCV infection is associated with serious liver disease in haemophilic patients, but so far this has been restricted to a minority of those at risk. HIV co-infection accelerates progression to hepatic decompensation, and we speculate that this is probably due to enhanced HCV replication in the presence of immune deficiency.

Adolescent↗

Exercise and dietary modification with women of non-English speaking background: a pilot study with Polish-Australian women.

Health promotion programs aimed at the general community often fail to reach Australians of non-English speaking background (NESB) because of language and cultural barriers. A 12-week minimal-intervention heart health program, designed for women of European background, was piloted with 43 women from a Polish social group, with a further 30 women serving as a comparison group. Assessments of the intervention group before and after the 12-week program indicated significant decreases in exercising heart rate and in resting blood pressure, which were not evident in the comparison group. Twelve-week follow-up data indicated that these gains had been well maintained. When the comparison group was invited to participate in a similar program, there were also significant improvements on these variables. This pilot study suggests that health promotion programs aimed at NESB Australians can be effective in modifying risk factors for cardiovascular disease if an effort is made lo address language and cultural barriers.

Journal Article↗

Apoptosis in decidual tissue regression and reorganization.

During blastocyst implantation, cellular degeneration of decidual tissue spreads from the antimesometrial region to the mesometrial region to accommodate the developing conceptus. To identify the mechanism of decidual regression and its tissue localization, decidual formation was induced in either intact pseudopregnant rats or ovariectomized rats treated with steroids. Antimesometrial and mesometrial cells were separated by elutriation and cultured for 48 h before DNA analysis. Nucleosomal DNA fragmentation was observed in antimesometrial cells, whereas DNA fragmentation was less marked in mesometrial cells. To determine whether a similar pattern of apoptosis occurred during decidual development in vivo, decidua tissues from antimesometrial and mesometrial regions were obtained on days 8-14. Nucleosomal DNA fragmentation was first detected on day 10 in the antimesometrial region, with fragmentation in the mesometrial region delayed by at least 24 h. DNA fragmentation increased in both tissues with time, but was always more pronounced in antimesometrial cells. Sulfated glycoprotein-2 (SGP-2) has been associated with apoptosis, and its expression was examined by Northern analysis. Levels of SGP-2 messenger RNA (mRNA) were detected in the antimesometrial region on day 9 and increased markedly by day 10; mesometrial expression was delayed 24 h. Levels of SGP-2 mRNA in both regions decreased before the onset of DNA fragmentation. In contrast, cathepsin-D expression, detected by immunohistochemistry, was localized to few mesometrial and antimesometrial cells between days 9-12, with all cells showing extensive staining by day 14. To determine whether changes in progesterone control mechanisms initiated decidual apoptosis, plasma progesterone levels were measured by RIA, and progesterone receptor mRNA levels in decidual tissues were examined by reverse transcription-polymerase chain reaction. Both parameters remained unchanged during decidual growth and regression. These results provide biochemical evidence that decidual regression occurs by apoptosis initiated in the antimesometrial region and with progression to the mesometrial region. Apoptotic cell death occurs despite high levels of plasma progesterone and high levels of progesterone receptor message in decidual tissue.

Animals↗

Role of the extracellular regions of the parathyroid hormone (PTH)/PTH-related peptide receptor in hormone binding.

The PTH/PTH-related peptide receptor is a member of a newly discovered family of G-protein-coupled receptors. Strikingly conserved features among these receptors include the positioning of eight extracellular cysteines and several other residues that are located predominantly within the membrane-embedded region. Deletion mutants or receptors with point mutations of the highly conserved cysteine residues were transiently expressed in COS-7 cells to evaluate PTH binding and PTH-stimulated cAMP production. Deletion of residues 61-105, which are encoded by exon E2 in the PTH/PTH-related peptide receptor gene, did not affect receptor function. An epitope derived from Haemophilus influenza hemagglutinin was, therefore, introduced into this portion of most receptors to allow the independent assessment of cell surface expression. PTH binding capacity was not reduced by the deletion of residues 258-278 in the first extracellular loop. Receptors with deletion of either residues 31-47 in the amino-terminal extension or residues 431-440 in the third extracellular loop failed to bind PTH, although expression of the receptor on the cell surface was only marginally reduced. Most other receptor mutants, including those in which each of the six cysteines in the amino-terminus was replaced by serines, failed to be processed and/or expressed appropriately, whereas the substitution of cysteine-281 or -351 had a less severe effect. The combined replacement of both cysteines concomitantly increased PTH binding and cell surface expression, suggesting the formation of a disulfide bond between these two residues. Our data indicate that residues near the amino-terminus and within the third extracellular loop are necessary for ligand binding, whereas more than 25% of the receptor's extracellular region appears not to be involved.

Amino Acid Sequence↗

[Effects of handgrip work and heat load on heart rate variability].

The purpose of the present study was to evaluate cardiac sympathetic (SNS) and parasympathic (PNS) nervous system activities during isometric continuous and intermittent handgrip with power spectrum analysis of heart rate variability (HRV). Eight healthy men performed work at 10% maximum voluntary contraction. The sequence of tests included three different work patterns: 1) the continuous handgrip for 30 min, 2) the intermittent handgrip (10 sec contraction +5 sec relaxation) for 45 min, 3) the intermittent handgrip (10 sec contraction +10 sec relaxation) for 60 min. These experiments were performed at two different heat loads (25 degrees C and 40 degrees C, R.H. 50%). To evaluate HRV, low frequency component (0.03-0.15Hz: LFP) and high frequency component (0.15-0.5Hz: HFP) power were calculated. The SNS and PNS activities were evaluated by LFP/HFP and HFP/(HFP + LFP), respectively. Summary of the results was shown below. 1) The change of the SNS and PNS activities were not significant among the different work patterns, due to the lower work load in the present experiment. 2) The increase of HR at 25 degrees C was mediated primarily by the decrease of the PNS activities during the work periods. 3) The effects of heat loads on the SNS and PNS activities were significant. Briefly, at the same work pattern, the SNS activities at 40 degrees were higher than those at 25 degrees C, but the PNS activities at 40 degrees C were lower than those at 25 degrees C.

Adult↗

[Localized muscular load to different work patterns and heat loads during handgrip].

The physiological responses and the magnitude of perceived fatigue (MPF) were estimated from eight healthy men during isometric continuous and intermittent handgrip at 10% maximum voluntary contraction (MVC). The physiological responses involved electromyogram (EMG), heart rate (HR), mean blood pressure (MBP) and forearm blood flow during contraction (FBFC) and relaxation (FBFR). The sequence of tests included three different work patterns: 1) continuous handgrip for 30 min, 2) intermittent handgrip (10 sec contraction +5 sec relaxation) for 45 min, 3) intermittent handgrip (10 sec contraction +10 sec relaxation) for 60 min. These experiments were performed on two different heat loads (25 degrees C and 40 degrees C, H.R. 50%). The results were as follows: 1) The localized muscle fatigue in the forearm was observed during the work periods. 2) The mean frequency of EMG was higher at 40 degrees C than 25 degrees C. 3) FBFR was significantly lower than FBFC at 40 degrees C. 4) MPF and MBP were little influenced by the heat load. 5) MPF correlated well with both HR and MBP.

Adult↗

Perceived prestige and health careers recruitment.

Perceived occupational prestige is an important factor in career choice. The purpose of this study was to obtain prestige ratings of 13 allied health occupations and 13 general occupations for high school students, community college students (nonhealth majors), and community college health occupations students. The obtained ratings were compared with ratings of a combined group of health care providers. There was little agreement among the groups as to level of prestige. The high school rankings were the most disparate. Career exploration and outreach programs as part of recruitment efforts by health care institutions are suggested.

Adolescent↗

CD4+ counts before and after switching to monoclonal high-purity factor VIII concentrate in HIV-infected haemophilic patients.

Allogenic proteins that contaminate intermediate purity clotting factor concentrates may activate the immune system of HIV-infected haemophilic patients. In 37 haemophilic patients infected with HIV who had originally been treated with intermediate purity factor VIII concentrate and then changed to monoclonally-purified high purity factor VIII concentrate the rates of CD4+ decline (10(9)/l per year) were 0.06 before and 0.02 after a switch to high purity products (p = 0.01). The median follow-up of patients after the switch to high purity products was 1.7 years (range 0.2 to 3 years). This significant change in the rate of CD4 decline was independent of the starting CD4 count, age and antiretroviral therapy. This result is consistent with those from randomised trials of the introduction of high-purity concentrate. Given the strong association between the CD4+ count and survival, treatment with high purity rather than intermediate purity clotting factor concentrate may confer a survival benefit for HIV-infected haemophilic patients.

AIDS-Related Opportunistic Infections↗

Antitumor activity of nigericin and 5-(N-ethyl-N-isopropyl)amiloride: an approach to therapy based on cellular acidification and the inhibition of regulation of intracellular pH.

The extracellular pH (pHe) in solid tumors is frequently lower than the pHe in normal tissues, but the intracellular pH (pHi) is regulated to physiological levels. Cell killing can be achieved in an acidic environment in tissue culture by nigericin, which acidifies cells by transporting H+ from the extracellular space into the cytoplasm; this cell killing can be enhanced when used with 5-(N-ethyl-N-isopropyl)amiloride (EIPA), a potent inhibitor of membrane-based Na+/H+ exchange, which plays a major role in the regulation of pHi (R. P. Maidorn; E. J. Cragoe; I. F. Tannock, Br. J. Cancer 67:297-303; 1993). We have therefore assessed the ability of nigericin and EIPA to kill cells in two murine solid tumors (the KHT fibrosarcoma and the EMT-6 sarcoma). Hydralazine, which reduces tumor blood flow, or glucose, which stimulates glycolysis leading to accumulation of lactate, were also administered to mice to lower pHe in the tumors. We observed only a small decrease in the surviving fractions of cells in the tumors when tolerated doses of nigericin and EIPA were given IP to tumor-bearing mice. When nigericin and EIPA were combined with administration of hydralazine, the surviving fraction of cells in both tumors was reduced by a factor of 0.01, but there were minimal effects on growth delay. Administration of glucose with nigericin and EIPA led to a smaller reduction in surviving fraction of the KHT tumor (by approximately 0.1), although glucose was more effective than hydralazine in lowering the mean tumor pHe. When KHT tumors were treated with 15 Gy X-rays followed immediately by nigericin, EIPA, and hydralazine, a reduced surviving fraction as well as an increase in tumor growth delay was observed compared to radiation alone; however, there was little evidence to suggest that these agents were selectively toxic to the cells that survived radiation. Nigericin and EIPA, with or without hydralazine, had minimal effects on normal tissues, as assessed by changes in body weight, number of leukocytes, and serum creatinine levels. We conclude that pharmacological effects to acidify cells and to prevent regulation of pHi under the acidic conditions that exist in solid tumors can lead to moderate levels of cell killing, if additional strategies are used to lower tumor pHe.

Amiloride↗

The behavioral effects of the stereoisomers of 4-methylaminorex, a psychostimulant, in the rat.

In this study, we examined the effect of the isomers of the psychostimulant 2-amino-4-methyl-5-phenyl-delta 2-oxazoline (4-methylaminorex or 4-MAX) on behavior in rats. The s.c. administration of the stereoisomers of 4-MAX, trans-4S,5S, cis-4R,5S, cis-4S,5R and trans-4R,5R (0.3-3 mg/kg), produced a dose-dependent increase in locomotor activity. However, at a dose of 10 mg/kg, the isomers of 4-MAX produced an initial increase in locomotor activity followed by the appearance of stereotyped behaviors (continuous sniffing, chewing, head bobbing, etc.) then a subsequent phase of rebound-enhanced locomotor activity all over a time course of 4 hr. The rank order of potency for the stereoisomers of 4-MAX was: 4S,5S > 4R,5S =4S,5R < 4R,5R. To determine what neurotransmitter systems may mediate the action of 4-MAX, the ability of various receptor antagonists to block or attenuate the effect of trans-4S,5S-4-MAX (3 mg/kg s.c.) on locomotor activity was examined. The selective dopamine (DA) D1 antagonist (-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H- benzo- [d]naph-thio[2,1b]azepine (SCH 39166) and the D2 receptor antagonist (-)-eticlopride significantly, attenuated the behavioral action of trans-4S,5S-4-MAX, whereas antagonists to serotonergic and adrenergic receptors were ineffective. These results suggest that the ability of 4S,5S-4-MAX to induce locomotor hyperactivity and stereotypical behaviors and to increase rearing durations is primarily mediated by DA receptors. To determine whether the action of 4-MAX is dependent upon 5-hydroxytryptamine or DA concentrations in nerve terminals, rats were pretreated with either reserpine, alpha-methyl-p-tyrosine or d,l-p-chlorophenylalanine. Both reserpine and alpha-methyl-p-tyrosine pretreatment markedly attenuated the locomotor activity produced by trans-4S,5S-4-MAX. Moreover, L-dopa partially reversed the inhibitory action of alpha-methyl-p-tyrosine on 4S,5S-4-MAX-induced behavioral activation. In contrast, the administration of d,l-p-chlorophenylalanine did not alter the behavioral responses produced by trans-4S,5S-4-MAX. Taken together, our results suggest that 4-MAX may increase several locomotor behaviors by inducing neuronal DA release, which subsequently interacts with dopaminergic receptors.

Animals↗