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Biomedical subjects

M Franklin

Publications and source records attributed to M Franklin.

At least 19 recordsLinked to original sources
PubMed2003

Postoperative cell mediated immune response is better preserved after laparoscopic vs open colorectal resection in humans.

BACKGROUND: Animal studies have documented significantly better preserved postoperative cell-mediated immune function, as measured by serial delayed-type hypersensitivity (DTH) challenges, after laparoscopic-assisted than after open bowel resection. Similarly, in humans, the DTH responses after open cholecystectomy have been shown to be significantly smaller than preoperative responses; whereas after laparoscopic cholecystectomy, no significant change in DTH response has been noted. The purpose of this study was to assess cell-mediated immune function via serial DTH skin testing in patients undergoing laparoscopic or open colectomy. METHODS: A total of 35 subjects underwent either laparoscopic (n = 18) or open colectomy (n = 17) in this prospective but not randomized study. Only patients who were judged to be immunoresponsive by virtue of having responded successfully to a preoperative DTH challenge were eligible for entry in the study. DTH challenges were carried out at three time points in all patients: preoperatively, immediately following surgery, and on the third postoperative day (POD 3). Responses were measured 48 h after each challenge and the area of induration calculated. There were no significant differences between the laparoscopic (LC) and open (OC) colorectal resection groups in regard to demographics, indications for surgery, or type of resection carried out. The percentage of patients transfused was similar in both groups (17%, LC; 12% OC; p = NS). In the LC group, all cases were completed without conversion using minimally invasive methods. There were no perioperative deaths, and the rate of postoperative complications was similar in both groups. The preoperative and postoperative DTH results were analyzed and compared within each surgical group using several methods. RESULTS: In regards to the OC group results, the median sum-total DTH responses for the day of surgery challenges (0.44 +/- 69 cm2) and the POD 3 challenges (0.72 +/- 3.37 cm2) were significantly smaller than the preoperative results (3.61 +/- 3.83 cm2, p <0.0005 vs op day and p <0.0003 vs POD 3 results). When the LC group results were similarly analyzed, no significant difference in DTH response was noted between the pre- and the postoperative challenge results. Additionally, when the median percent change from baseline was calculated and considered for the OC group's DTH results, both postoperative challenge time points demonstrated significantly decreased responses when compared to their preoperative results (vs day of surgery, p <0.007; vs POD 3, p <0.006). Similar analysis of the LC group's results yielded nonsignificant differences between the pre- and postoperative responses. Lastly, when the LC and the OC groups median percent change from baseline results were directly compared for each of the postoperative challenges, a significant difference was noted for the POD 0 challenge (LC, -21%; OC 88%; p <0.004) but not for the POD 3 challenge. CONCLUSIONS: The postoperative DTH responses of the open surgery patients were significantly smaller than their preoperative responses. This was not the case for the laparoscopic group (a combination of fully laparoscopic and laparoscopic-assisted resections). When the open and laparoscopic groups results are directly compared, regarding the results of the day of surgery DTH challenges, the LC groups median percent change from baseline was significantly less than that observed in the OC group. These results imply that open colorectal resection is associated with a significant suppression of cell-mediated immune response postoperatively, whereas in this study laparoscopic colorectal resection was not. Further human studies are needed to verify these findings and to determine the clinical significance, if any, of this temporary difference in immune function following colon resection.

Antigens, Fungal↗
PubMed2002

Simultaneous measurement of zolmitriptan and its major metabolites N-desmethylzolmitriptan and zolmitriptan N-oxide in human plasma by high-performance liquid chromatography with coulometric detection.

Zolmitriptan, N-desmethylzolmitriptan, zolmitriptan N-oxide and an internal standard (an analogue of zolmitriptan) were extracted from plasma by a solid-phase extraction (SPE). Chromatography was performed using isocratic reversed-phase high-performance liquid chromatography (HPLC) with coulometric end-point detection. The standard curves were linear over the range 2-20 ng/ml for zolmitriptan and its metabolites in plasma. The mean inter- and intra-assay coefficients of variation over the range of the standard curves were less than 11%. The absolute recovery averaged 87, 58 and 77% for zolmitriptan. N-desmethylzolmitriptan and zolmitriptan N-oxide, respectively. The assay sensitivity was 0.5 ng for each analyte.

Chromatography, High Pressure Liquid↗
PubMed2001

Chromium treatment decreases the sensitivity of 5-HT2A receptors.

RATIONALE: Recent case series suggest that chromium picolinate in doses of 400 microg daily may have antidepressant properties, perhaps through increasing the peripheral availability of tryptophan for brain serotonin (5-HT) synthesis. OBJECTIVES: To determine the effects of chromium treatment on plasma tryptophan availability and on brain 5-HT function in human and animal models. METHODS: We studied the effects of short-term chromium supplementation on plasma concentrations of tryptophan and other large neutral amino acids. Brain 5-HT function was assessed by measuring the corticosterone/cortisol response to the 5-HT precursor, 5-hydroxytryptophan (5-HTP), a response believed to be mediated via indirect activation of 5-HT(2A) receptors. RESULTS: In rats, chromium increased peripheral and central tryptophan availability and elevated brain 5-HT content. Changes in peripheral tryptophan availability were not seen in humans but in both rats and humans, chromium lowered the cortisol response to challenge with 5-HTP. CONCLUSIONS: Chromium can modify brain 5-HT function in humans and animals, perhaps by altering the sensitivity of central 5-HT(2A) receptors.

Adult↗
PubMed2001

Researching the antidepressant actions of Hypericum perforatum (St. John's wort) in animals and man.

We have studied the effect of acute and sub-chronic treatments of a formulation of a methanolic extract of hypericum perforatum (HP, also known as St John's wort) on plasma hormones and brain neurotransmitters in healthy human volunteers and rats. Also studied were the effects of equivalent acute doses of two constituents of HP (with respect to LI 160 extract), hypericin and hyperforin in rats. In acute treatment studies in normal volunteers subjects received 9 tablets of the finished product Jarsin 300 and placebo in the pilot study (unblinded) and in the main study (a double blind, balanced order, cross-over design). Results in normal volunteer studies show that HP caused significant increases of salivary cortisol and plasma growth hormone (GH) whereas it decreased plasma prolactin versus placebo. Plasma hormone levels were associated with a rise in plasma hyperforin but not with hypericin, however no significant correlation was found. In the animal studies, acute treatment with LI 160, hyperforin and hypericin all caused significant increases in plasma corticosterone. This was associated with significant increases in brain cortical tissue 5-HT content. The corticosterone responses were attenuated by the 5-HT2 receptor antagonist, ketanserin but not by the 5-HT1A antagonist, WAY-100635. This suggests that the corticosterone responses may be mediated via a 5-HT2 mechanism of action. When sub-chronic and acute treatment using two different doses of LI 160 were compared, plasma corticosterone level were significantly decreased. Thus suggesting a down-regulation or desensitisation of post-synaptic 5-HT2 receptors. Plasma prolactin was significantly reduced by acute treatment with LI 160 and hyperforin treatment but not by hypericin. This was associated with a concomitant rise in brain cortical tissue DA. Both LI 160 and hyperforin treatments decreased the plasma prolactin responses to the DA antagonist, haloperidol, suggesting that this may be associated with a DA-mediated mechanisn of action. When acute and sub-chronic treatments were compared, plasma prolactin responses were increased in the sub-chronically treated animals. The studies when taken together suggest that the LI 160 extract may effect plasma hormonal changes via both 5-HT and DA-mediated mechanisms but do not involve noradrenaline (NA). The data also suggests that hyperforin may be more important than hypericin for effecting these changes following acute treatment. Further studies investigating both acute and sub-chronic effects of these compounds are necessary.

Adult↗
PubMed2001

Effect of a low tryptophan diet on the prolactin responses to the 5-HT2A agonist DOI in the rat.

Low tryptophan (TRP) diets decrease brain serotonin (5-HT) content and produce an up-regulation of the function of some but not all 5-HT receptor subtypes. The aim of the present study was to assess the effect of a two week low TRP containing diet on the plasma prolactin (PRL) response to the 5-HT2A receptor agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI) in the rat. The low TRP diet significantly reduced plasma total TRP as well as brain 5-HT for the two weeks of the study although plasma free TRP was decreased only for the first week of the diet. The PRL response to DOI was significantly increased in the first week of the diet but returned to normal in the second. The results suggest that a low TRP diet produce a transient up-regulation of brain 5-HT2A receptors.

Amphetamines↗
PubMed2001

Are the proposed limits of energy intake:basal metabolic rate and dietary nitrogen:urinary nitrogen ratios suitable for validation of food intake?

The validity of 7 d weighed records of diet obtained for pre-menopausal Mexican women was assessed by two independent methods: the energy intake:BMR (EI:BMR) and the dietary N:urinary N (DN:UN). For the latter, complete urine collections are required and completeness was assessed from measurements of para-aminobenzoic acid (PABA) excretion. There were forty-six adult female subjects in the study, thirty-four were from Mexico City and twelve were from a rural population in the Central Highlands, Mexico. However, data were rejected from five urban women for whom the PABA excretion data suggested incomplete urine collection on four or more days. BMR was measured with Oxylog portable O2 consumption meters, and physical activity level was assessed from a self-completed activity diary. An approximate relationship between the EI:BMR ratio and the DN:UN ratio suggested that the rejection limits on the EI:BMR ratio recommended by are wider than the limits on the DN:UN ratio recommended by. Using the recommended cut-off points for EI:BMR but wider limits for DN:UN, twenty-one and twenty-five women respectively had acceptable intake records by the two methods, and sixteen of them by both methods. In conclusion the modification of the DN:UN limits to 0.92 and 1.70 to set acceptable intake values makes the use of measurements of N and energy balance comparable. Urine values with PABA recoveries greater than should be rejected, as should UN values validated by less than 3 d.

Adult↗
PubMed2001

Role of alginate O acetylation in resistance of mucoid Pseudomonas aeruginosa to opsonic phagocytosis.

Establishment and maintenance of chronic lung infections with mucoid Pseudomonas aeruginosa in patients with cystic fibrosis (CF) require that the bacteria avoid host defenses. Elaboration of the extracellular, O-acetylated mucoid exopolysaccharide, or alginate, is a major microbial factor in resistance to immune effectors. Here we show that O acetylation of alginate maximizes the resistance of mucoid P. aeruginosa to antibody-independent opsonic killing and is the molecular basis for the resistance of mucoid P. aeruginosa to normally nonopsonic but alginate-specific antibodies found in normal human sera and sera of infected CF patients. O acetylation of alginate appears to be critical for P. aeruginosa resistance to host immune effectors in CF patients.

Acetylation↗
PubMed2001

Cognitive-behavioral psychotherapy for pediatric obsessive-compulsive disorder.

Discusses the cognitive-behavioral psychotherapy for pediatric obsessive-compulsive disorder (OCD). Over the past 15 years, cognitive-behavioral psychotherapy has emerged as the psychosocial treatment of choice for OCD across lifespan. Unlike other psychotherapies that have been applied usually unsuccessfully to OCD, cognitive-behavioral treatment (CBT) presents a logically consistent and compelling relationship between the disorder, the treatment, and the specified outcome. Nevertheless, despite a consensus that CBT is usually helpful, clinicians routinely complain that patients will not comply with behavioral treatments and parents routinely complain that clinicians are poorly trained in CBT, with the result that many if not most children and adolescents are denied access to effective psychosocial treatment. This unfortunate situation may be avoidable, given an increased understanding regarding the implementation of CBT in children and adolescents with OCD. To this end, we review the principles and the practical aspects of the cognitive-behavioral treatment of OCD in youth, move on to discuss empirical studies supporting the use of CBT in the pediatric age group, and conclude by discussing directions for future research.

Adolescent↗
PubMed2000

Enzyme-catalyzed acylation of homoserine: mechanistic characterization of the Haemophilus influenzae met2-encoded homoserine transacetylase.

The first unique step in bacterial and plant methionine biosynthesis involves the acylation of the gamma-hydroxyl of homoserine. In Haemophilus influenzae, acylation is accomplished via an acetyl-CoA-dependent acetylation catalyzed by homoserine transacetylase. The activity of this enzyme regulates flux of homoserine into multiple biosynthetic pathways and, therefore, represents a critical control point for cell growth and viability. We have cloned homoserine transacetylase from H. influenzae and present the first detailed enzymatic study of this enzyme. Steady-state kinetic experiments demonstrate that the enzyme utilizes a ping-pong kinetic mechanism in which the acetyl group of acetyl-CoA is initially transferred to an enzyme nucleophile before subsequent transfer to homoserine to form the final product, O-acetylhomoserine. The maximal velocity and V/K(homoserine) were independent of pH over the range of values tested, while V/K(acetyl)(-)(CoA) was dependent upon the ionization state of a single group exhibiting a pK value of 8.6, which was required to be protonated. Solvent kinetic isotope effect studies yielded inverse effects of 0.75 on V and 0.74 on V/K(CoA) on the reverse reaction and effects of 1.2 on V and 1.7 on V/K(homoserine) on the forward reaction. Direct evidence for the formation of an acetyl-enzyme intermediate was obtained using rapid-quench labeling studies. On the basis of these observations, we propose a chemical mechanism for this important member of the acyltransferase family and contrast its mechanism with that of homoserine transsuccinylase.

Acetyltransferases↗
PubMed2000

S-adenosylmethionine and Pneumocystis carinii.

We previously reported that S-adenosylmethionine (AdoMet), a key molecule in methylation reactions and polyamine biosynthesis, enhances axenic culture of the AIDS-associated opportunistic fungal pathogen Pneumocystis carinii. Here we report that AdoMet is absolutely required for continuous growth. Two transporters are present, one high affinity, K(m) = 4.5 microm, and one low affinity, K(m) = 333 microm. The physiologically relevant high affinity transporter has a pH optimum of 7.5 and no related natural compounds compete for uptake. Transport is 98% inhibited at 4 degrees C, 24% inhibited by 20 mm sodium azide, and 95% inhibited by the combination of 20 mm sodium azide and 1 mm salicylhydroxamic acid; thus transport is active and dependent on both a cytochrome chain and an alternative oxidase. In vitro, AdoMet is used at a rate of 1. 40 x 10(7) molecules cell(-1) min(-1). AdoMet synthetase activity was not detected by a sensitive radiolabel incorporation assay capable of detecting 0.1% of the activity in rat liver. In addition, the AdoMet plasma concentration of rats is inversely correlated with the number of P. carinii in the lungs. These findings demonstrate that P. carinii is an AdoMet auxotroph. The uptake and metabolism of this compound are rational chemotherapeutic targets.

Animals↗
PubMed2000

Simian virus 40 large T antigen binds a novel Bcl-2 homology domain 3-containing proapoptosis protein in the cytoplasm.

A 193-kDa SV40 large T antigen (T-Ag)-binding protein, designated p193, was identified and cloned. Inspection of the deduced amino acid sequence revealed the presence of a short motif similar to the Bcl-2 homology (BH) domain 3, suggesting that p193 may be a member of a family of apoptosis promoting proteins containing only BH3 motifs. In support of this, p193 expression promoted apoptosis in NIH-3T3 cells. Deletion of the BH3 motif abolished p193 apoptosis activity. p193-induced apoptosis was antagonized by co-expression of Bcl-X(L). Immune cytologic analysis indicated that p193 is localized to the cytoplasm of transfected cells. p193-induced apoptosis was also antagonized by co-expression of T-Ag, which resulted in the cytoplasmic localization of both proteins. The p193 binding site was mapped to an N-terminal region of T-Ag previously implicated in transforming activity. These results suggest that T-Ag possesses an antiapoptosis activity, independent of p53 sequestration, which is actuated by T-Ag/p193 binding in the cytoplasm.

3T3 Cells↗
PubMed2000

Exposure to immunization media messages among African American parents.

BACKGROUND: African Americans have low immunization rates, yet little is known about their immunization knowledge, attitudes, and practices or about the effect of outreach to this audience. In Spring 1997, the California Department of Health Services (CDHS) launched a statewide culturally sensitive and ethnically specific media campaign directed toward African Americans. This campaign was preceded by a major Los Angeles County Department of Health Services media campaign. OBJECTIVES: The objectives of this study were to (a) estimate exposure to immunization media messages among African Americans; (b) determine sources of immunization information; and (c) assess various immunization attitudes and beliefs in order to refine future outreach efforts. METHODS: Following the CDHS media campaign, a random digit dial survey was conducted with 801 African American families with children under age 10. The sample was drawn from the four California regions with the highest African American birth rates. It included all zip codes in these regions with greater than 150 African American births per year. Lower bound response rates ranged from 62.5 to 76.1%. Higher income and education levels were overrepresented. Results were weighted to adjust for this. RESULTS: Over 88% remembered seeing or hearing some form of immunization information. Exposure to television ads was reported by 63% followed by billboards (51%) and radio (42%). Sixty-two percent thought mild disease was possible after shots; 27% feared HIV from needles and 19% thought pain was a barrier. Respondents who cited money as a barrier (26%) were less likely to believe that shots were available for free (P = 0.02). CONCLUSIONS: Media advertising is an effective tool for reaching African Americans. Addressing specific concerns (e.g., clarification of the circumstances and likelihood of getting a mild case of the disease following an immunization, availability of free shots, and risk of HIV) may contribute to increased immunization rates for this population.

Black or African American↗
PubMed2000

Communication breakdown in the outpatient referral process.

OBJECTIVE: To evaluate primary care and specialist physicians' satisfaction with interphysician communication and to identify the major problems in the current referral process. DESIGN: Surveys were mailed to providers to determine satisfaction with the referral process; then patient-specific surveys were e-mailed to this group to obtain real-time referral information. SETTING: Academic tertiary care medical center. PARTICIPANTS: Attending-level primary care physicians (PCPs) and specialists. MEASUREMENTS AND MAIN RESULTS: The response rate for mail surveys for PCPs was 57% and for specialists was 51%. In the mail survey, 63% of PCPs and 35% of specialists were dissatisfied with the current referral process. Respondents felt that major problems with the current referral system were lack of timeliness of information and inadequate referral letter content. Information considered important by recipient groups was often not included in letters that were sent. The response rate for the referral specific e-mail surveys was 56% for PCPs and 53% for specialists. In this e-mail survey, 68% of specialists reported that they received no information from the PCP prior to specific referral visits, and 38% of these said that this information would have been helpful. In addition, four weeks after specific referral visits, 25% of PCPs had still not received any information from specialists. CONCLUSIONS: Substantial problems were present in the referral process. The major issues were physician dissatisfaction, lack of timeliness, and inadequate content of interphysician communication. Information obtained from the general survey and referral-specific survey was congruent. Efforts to improve the referral system could improve both physician satisfaction and quality of patient care.

Ambulatory Care↗
PubMed2000

Acute effects of LI 160 (extract of Hypericum perforatum, St John's wort) and two of its constituents on neuroendocrine responses in the rat.

Extracts of Hypericum perforatum (St John's wort), such as LI 160, which are effective antidepressants have several active constituents. Their mode of action in depression, however, is unclear. In the present investigation, we assessed the effect of equivalent doses of LI 160 and two of its components, hypericin and hyperforin on serotonin (5-HT) and dopamine (DA)-mediated neuroendocrine responses in the rat. LI 160, hypericin and hyperforin significantly and equivalently increased plasma corticosterone. This effect was blocked by ketanserin but not WAY-100635, suggesting mediation via 5-HT2 receptors. LI 160 also lowered plasma prolactin and prevented the increase in plasma prolactin following haloperidol administration. Hyperforin had a similar but somewhat less pronounced effect. We conclude that LI 160, hypericin and hyperforin all increase 5-HT-mediated corticosterone release while LI 160 enhances DA-mediated inhibition of prolactin release. Hyperforin may contribute to the facilitatory effect of LI 160 on DA function, but hypericin does not.

Animals↗
PubMed1999

Measurement of hyperforin a constituent of St. John's wort in plasma by high-performance liquid chromatography.

Hyperforin is a constituent of Hypericum perforatum extracts (St. John's wort, H. perforatum), which have antidepressant action. Hyperforin was extracted from plasma utilising a solid-phase extraction procedure. Chromatography was performed by isocratic reversed-phase high-performance liquid chromatography with UV end-point detection. The calibration curve was linear over the range 0.15-3 microg per ml of plasma. The sensitivity for hyperforin was 4.5 ng on-column. Mean inter- and intra-assay relative standard deviations over the range of the standard curve were less than 5%. The absolute recovery for hyperforin averaged 97.8%.

Animals↗
PubMed1999

Simultaneous determination of catecholamines in rat brain tissue by high-performance liquid chromatography.

A novel and highly sensitive method has been developed for the determination of catecholamines [noradrenaline (NA), dopamine (DA), serotonin (5-HT) and their metabolites 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA)] in brain tissue. The method uses isocratic reversed-phase HPLC with amperometric end-point detection. The calibration curve was linear over the range 10-150 pg on-column. The assay limits of detection for NA, DA, 5-HT, 5-HIAA and HVA were 3.8, 3.8, 6.8, 5 and 7.5 pg on-column, respectively. The mean inter- and intra-assay relative standard deviations (RSDs) over the range of the standard curve were less than 5%. The absolute recoveries averaged 99.1%, 99.5%, 97.7%, 99.5% and 98.8% for NA, DA, 5-HT, 5-HIAA and HVA, respectively.

Animals↗
PubMed1999

Neuroendocrine evidence for dopaminergic actions of hypericum extract (LI 160) in healthy volunteers.

BACKGROUND: We studied the effect of a single dose of a formulation of a methanolic extract of Hypericum perforatum (HP), also known as St. John's wort, on plasma concentrations of growth hormone (GH), prolactin (PRL), and cortisol (CORT) in 12 healthy male volunteers. METHODS: Subjects received 9 tablets of the finished product Jarsin 300 and placebo in a double-blind, balanced-order, cross-over design. RESULTS: Following HP relative to placebo, there was a significant increase in plasma GH and a significant decrease in plasma PRL. Plasma CORT levels were unchanged. CONCLUSIONS: Taken together with data from animal experimental studies, the findings suggest that this dose of HP may increase some aspects of brain dopamine function in humans.

Adult↗