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Biomedical subjects

P J Brown

Publications and source records attributed to P J Brown.

At least 19 recordsLinked to original sources
PubMed1998

Assessment of intestinal function in cats with chronic diarrhea after infection with feline immunodeficiency virus.

OBJECTIVE: To identify consistent relevant mechanisms of small intestinal dysfunction in cats with experimentally induced feline immunodeficiency virus infection (FIV) that developed chronic diarrhea during the time they were being used in studies of pathogenicity and transmission of FIV. ANIMALS: 10 cats. PROCEDURE: The following investigative tests and techniques were performed on each of the cats: routine hematologic and serum biochemical analyses; urinalysis; fecal parasitologic and microbiologic examinations; breath hydrogen lactulose (BH2LT) and xylose (BH2XT) tests; intestinal permeability test; endoscopic examination of the intestinal mucosa; bacteriologic culture of endoscopically collected small intestinal juice; and histologic examination of endoscopically obtained intestinal biopsy specimens. RESULTS: Neutrophilia was evident in 3 cats, and lymphopenia was detected in 2 cats. Serum biochemical abnormalities were not observed. Urinalysis results were unremarkable. Fecal bacteriologic and parasitologic results were normal, except for isolation of Campylobacter sp from 1 cat. Abnormal BH2XT values suggestive of D-xylose malabsorption were identified in 2 cats, and BH2LT values indicated evidence of small intestinal bacterial overgrowth in 1 cat. Finally, permeability test results, quantitation of bacterial flora from the proximal part of the small intestine and histologic examination of biopsy specimens did not reveal any abnormalities. CONCLUSIONS: Enteric pathogens did not account for the development of diarrhea in cats with experimentally induced FIV infection, and consistent relevant mechanisms of small intestinal dysfunction were not identified.

Animals↗
PubMed1998

Failure-as-success: multiple meanings of eradication in the Rockefeller Foundation Sardinia project, 1946-1951.

In the history of malaria control programs there were important tensions between proponents of the concept of eradication and those of malaria control. In this debate the concept of eradication has had multiple meanings. This paper concerns the post-hoc interpretations of the outcomes of the Rockefeller International Health Foundation-sponsored project conducted in Sardinia between 1946 and 1951. The Ente Regionale per la Lotta Anti-Anofelica in Sardegna (regional agency for the anti-Anopheles struggle in Sardinia) (ERLAAS) project was conceived as a large-scale, field-based pilot demonstration project to test the feasibility of the strategy of "species eradication" in an area with an endemic malaria vector. Species eradication, a strategy championed by Soper, was aimed at the total annihilation of an anopheline vector from an area. Under the leadership of the Rockefeller Foundation, the ERLAAS project used postwar UNRRA funds to purchase local labor and imported DDT, oil-suspension, and war-surplus equipment in an "all-out" campaign against Anopheles labranchiae, even in sparsely populated areas. The original aim was entirely entomological; species eradication was expected to be completed in two years for a cost of $2.7 million. Ironically, malaria mortality on the island had already been lowered before WWII by a series of public health interventions. The ERLAAS project encountered severe technical and logistical difficulties; its ultimate failure was foreshadowed in the resignation of the first American director who doubted the feasibility of species eradication. Ultimately, the ERLAAS project was ended after four and a half years and an expenditure of $11.2 million. Although new malaria transmission on the island ended the project failed to eliminate A labranchiae. Finally, the regional government was counselled to continue mosquito control efforts; the continuation of a substantial mosquito control program for fifty years after this famous "malaria eradication" project runs contrary to the basic cost/benefit logic of the eradication concept. Nevertheless, in the popular press both in the U.S. and Italy, the project was presented and heralded as a major success in liberating the island from the age-old stranglehold and misery of malaria. In the course of the project, the goals of ERLAAS became transformed from species eradication to malaria eradication; this was an important political spin that was put on the evaluation of the program. The consequences of this tactical change in discourse included two important facts: the contribution of the Rockefeller Foundation to the island was exaggerated, and the legitimacy of the concept of global eradication was maintained. In the framework of the World Health Organization and the agreement for a global malaria eradication program, the "failure" of the Sardinia project was seldom recognized or mentioned. The technical, economic, and logistical problems faced by ERLAAS were very similar to the problems associated with the end of the WHO global malaria eradication policy in 1972. The Sardinia project is presented as a case of "failure-as-success"; an ideological transformation was made, not simply for local political expediency, but more importantly because of the predominance of the modernist cultural model of "progress through technology" that characterized international Public Health in the postwar era.

Animals↗
PubMed1997

Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma.

Peroxisome proliferator-activated receptors (PPARs) alpha and gamma are key regulators of lipid homeostasis and are activated by a structurally diverse group of compounds including fatty acids, eicosanoids, and hypolipidemic drugs such as fibrates and thiazolidinediones. While thiazolidinediones and 15-deoxy-Delta12, 14-prostaglandin J2 have been shown to bind to PPARgamma, it has remained unclear whether other activators mediate their effects through direct interactions with the PPARs or via indirect mechanisms. Here, we describe a novel fibrate, designated GW2331, that is a high-affinity ligand for both PPARalpha and PPARgamma. Using GW2331 as a radioligand in competition binding assays, we show that certain mono- and polyunsaturated fatty acids bind directly to PPARalpha and PPARgamma at physiological concentrations, and that the eicosanoids 8(S)-hydroxyeicosatetraenoic acid and 15-deoxy-Delta12,14-prostaglandin J2 can function as subtype-selective ligands for PPARalpha and PPARgamma, respectively. These data provide evidence that PPARs serve as physiological sensors of lipid levels and suggest a molecular mechanism whereby dietary fatty acids can modulate lipid homeostasis.

Animals↗
PubMed1997

Identification of peroxisome proliferator-activated receptor ligands from a biased chemical library.

BACKGROUND: The peroxisome proliferator-activated receptors (PPARs) were cloned as orphan members of the nuclear receptor superfamily of transcription factors. The identification of subtype-selective ligands for PPARalpha and PPARgamma has led to the discovery of their roles in the regulation of lipid metabolism and glucose homeostasis. No subtype-selective PPARdelta ligands are available and the function of this subtype is currently unknown. RESULTS: A three-component library was designed in which one of the monomers was biased towards the PPARs and the other two monomers were chosen to add chemical diversity. Synthesis and screening of the library resulted in the identification of pools with activity on each of the PPAR subtypes. Deconvolution of the pools with the highest activity on PPARdelta led to the identification of GW 2433 as the first high-affinity PPARdelta ligand. [3H]GW 2433 is an effective radioligand for use in PPARdelta competition-binding assays. CONCLUSIONS: The synthesis of biased chemical libraries is an efficient approach to the identification of lead molecules for members of sequence-related receptor families. This approach is well suited to the discovery of small-molecule ligands for orphan receptors.

Binding, Competitive↗
PubMed1997

Malaria, miseria, and underpopulation in Sardinia: the "malaria blocks development" cultural model.

Until the late Nineteenth century, endemic malaria was a serious public health problem in Sardinia, as in much of Southern Italy. As the poorest region of the new Italian nation, Sardinia was characterized by poor health, very low population densities, low agricultural productivity, and weak state authority associated with banditry. In this context, however, malaria was singled out as a key underlying problem for the situation of "internal underdevelopment." This paper describes the Italian scholarly literature about the relationship of malaria and economic productivity as a cultural model that can be labeled as "malaria blocks development" (MBD). Anti-malaria programs, including the state control of the distribution of quinine as well as land reclamation projects, played a major role in the decrease of malaria mortality in the first part of this century. Based on the logic of the MBD model, the decrease in malaria was expected to decrease an obstacle to "natural processes" of economic development. During the Fascist era, scientifically based antimalaria efforts formed a key element in centralized attempts for agricultural intensification and encouragement of immigration from over-populated parts of the country. Immediately after W.W.II, Sardinia was the site of a successful American-sponsored eradication project that represented one of the first uses of DDT against an indigenous anopheles vector. Hypotheses based on the MBD model about the nature of economic change after the removal of malaria are not supported. Nevertheless, variations of the MBD cultural model continue to be used in the field of International Health to the present day.

Animals↗
PubMed1997

Systemic treatment of severe psoriasis.

Severe psoriasis presents a difficult therapeutic challenge. Some modalities such as synthetic retinoids, phototherapy and methotrexate have been available for many years and need reappraisal, cyclosporin has only recently become available and requires careful administration. In this article we focus on the therapeutic modalities available to the dermatologist in Australia.

Cyclosporine↗
PubMed1997

Cystic thymoma in a cat with cholesterol-rich fluid and an unusual ultrasonographic appearance.

A cystic thymoma was identified in an eight-year-old domestic longhair cat with a chronic cough. Radiographs indicated a large mass of soft tissue density in the anterior thorax. Ultrasonography revealed an echogenic mass occupying the cranial and mid-thorax with a slight swirling movement of the echoes. Subsequent drainage under ultrasound guidance yielded a cholesterol-rich fluid. The mass was resected at exploratory thoracotomy and the diagnosis of thymoma confirmed. There was no sign of recurrence one year postoperatively. The clinical features and unusual laboratory findings are presented and compared with previously reported cases of thymomata in the cat.

Animals↗
PubMed1997

Lipomatous infiltration of the canine salivary gland.

Benign connective tumours of the canine salivary glands are rare. This report describes lipomatous infiltration of parotid or submandibular salivary glands in seven dogs in which the glands were enlarged as a result of infiltration by fat cells; they appeared to have been successfully treated by local excision. The precise cause of the lipomatous infiltration in the dogs is unclear but different causes of similar lesions in humans are discussed.

Animals↗
PubMed1997

Evaluating the terminology requirements to support multi-disciplinary diabetes care.

Diabetes mellitus is a multi-system disease requiring lifetime multi-disciplinary care, which has proven individual and economic benefits. The delivery of service involves co-operation and communication between patient, carer and health care professionals, and systematic auditing of processes and outcomes. Sustained improvement necessitates regular data acquisition, aggregation and analysis. The terminology requirements to support patient-centred records and identified datasets are examined, and differences in purpose and scope highlighted. The many stakeholders involved in diabetes care have their own sublanguages and terminology requirements which need harmonising around a common core. The problems and solutions of accommodating these needs are explored in relation to the Read Thesaurus.

Databases, Factual↗
PubMed1996

Effects of polyamines, polyamine analogs, and inhibitors of protein synthesis on spermidine-spermine N1-acetyltransferase gene expression.

The key polyamine catabolizing enzyme spermidine-spermine N1-acetyltransferase (SSAT) is among the few genes known to be inducible by the natural polyamines. Certain polyamine analogs markedly exaggerate this response and thus provide useful tools for studying the underlying regulatory mechanisms. As shown here, the analog which most potently induces SSAT activity, N1, N11-diethylnorspermine (DENSPM), increases SSAT mRNA in MALME-3M human melanoma cells to a maximum of > 20-fold and immunodetectable SSAT protein to > 300-fold. By comparison, the natural polyamine spermine is far less effective, increasing SSAT mRNA by approximately 3-fold and protein by approximately 7-fold. In particular, the difference in mRNA accumulation by spermine and the analog was shown to be due to differential effects on both gene transcription and mRNA stabilization. Although the analog DENSPM has been regarded as the most potent inducer of SSAT activity and mRNA, we now report that inhibitors of protein synthesis are capable of increasing SSAT mRNA to nearly comparable levels. Inhibitor-induced accumulation in SSAT mRNA was shown to involve increased gene transcription and mRNA stabilization. This suggests that, under basal conditions, SSAT gene expression is suppressed by a labile protein (or proteins). While induction of SSAT mRNA by inhibitors of protein synthesis only occurred at concentrations which blocked protein synthesis, that by DENSPM took place at concentrations which did not. The combination of either protein inhibitor with DENSPM or spermine produced an additive increase in SSAT mRNA. Taken together, these findings suggest the involvement of two separate but possibly converging pathways in the regulation of SSAT mRNA, one mediated by polyamines and their analogs and the other mediated by a labile repressor of SSAT gene transcription and/or mRNA stabilization. In addition to its apparent regulatory importance, induction of SSAT mRNA by inhibitors of protein synthesis represents a potentially useful system for studying the posttranscriptional regulation of this interesting gene.

Acetyltransferases↗
PubMed1996

Multisite phosphorylation of ornithine decarboxylase in transformed macrophages results in increased intracellular enzyme stability and catalytic efficiency.

Ornithine decarboxylase (ODC) is the initial inducible enzyme in the polyamine biosynthetic pathway. In the transformed macrophage-derived RAW264 cell line, ODC was overproduced and existed in both unphosphorylated and phosphorylated forms. To date, the only protein kinase known to phosphorylate mammalian ODC is casein kinase II (CKII). ODC was phosphorylated in vitro by CKII and subjected to exhaustive sequential proteolysis with trypsin and V8 protease. Two-dimensional peptide mapping showed only a single phosphopeptide; two-dimensional phosphoamino acid analysis of the phosphopeptide revealed only 32P-labeled serine. ODC was metabolically radiolabeled with 32Pi in RAW264 cells and also subjected to proteolysis, two-dimensional peptide mapping, and phosphoamino acid analysis. Two phosphopeptides were generated from the metabolically radiolabeled ODC, including one that migrated similarly to the peptide phosphorylated by CKII in vitro. Each of the in situ radiolabeled ODC peptides contained both 32P-labeled serine and threonine residues. Thus, in RAW264 cells, ODC is phosphorylated on at least one serine residue in addition to that phosphorylated by CKII and on at least two threonine residues. Phosphorylated ODC had an increased stability to intracellular proteolysis compared with unphosphorylated ODC, their half-lives being 49.2 +/- 3.78 and 23.9 +/- 2.6 min (p = 0.001), respectively. The phosphorylated and unphosphorylated forms of ODC were independently purified to homogeneity. Kinetic analysis revealed that the catalytic efficiency of the phosphorylated form of ODC was 50% greater than that of the unphosphorylated form; the unphosphorylated ODC had a Vmax of 20.54 +/- 1.65 micromol/min/mg, whereas the phosphorylated form had a Vmax of 30.61 +/- 2.6 micromol/min/mg (p = 0.005). Phosphorylation of ODC by CKII has no effect on enzyme activity. Taken together, these findings demonstrate that regulation of ODC activity is governed by as yet unidentified protein kinases.

Animals↗
PubMed1996

Breath hydrogen excretion by healthy cats after oral administration of oxytetracycline and metronidazole.

Breath hydrogen excretion over a period of three hours was measured to evaluate carbohydrate malassimilation in healthy cats treated orally with antibiotics. Both an absorbable carbohydrate (xylose) and a non-absorbable carbohydrate (lactulose) were administered during the tests to evaluate the changes in the intestinal mucosa and the population of bacteria within the intestinal lumen. Overall, the effects of oxytetracycline and metronidazole on breath hydrogen excretion were not significantly different. However, the treatment effect with an antibiotic did significantly change breath hydrogen excretion after xylose administration (P < 0.05) within groups. Similarly, with each antibiotic, breath hydrogen excretion was affected significantly (P < 0.001) by the time after the administration of the carbohydrate. Treatment with each antibiotic also interacted significantly with this time effect (P < 0.05) within groups. After lactulose administration, there was a trend within groups for the type of antibiotic to interact with the treatment effect on breath hydrogen excretion (P = 0.09). After oxytetracycline treatment, more hydrogen was exhaled during the first 120 minutes after lactulose administration than in the pre-antibiotic test, whereas after metronidazole treatment, less hydrogen was exhaled between 60 and 180 minutes after lactulose, administration. After treatment with either oxytetracycline or metronidazole, more hydrogen was exhaled after xylose administration. Obligate anaerobes could be isolated from samples of small intestinal fluid obtained endoscopically after oxytetracycline treatment, but they could not be isolated after treatment with metronidazole.

Administration, Oral↗
PubMed1996

Dysuria associated with urethral caruncle in the dog.

Three cases of urethral caruncle were recognized in bitches with a history of chronic dysuria. Clinical and radiological examinations revealed the presence of inoperable lesions involving much of the urethra in all three cases. At post-mortem examination of Case 1, an oval swelling, 1.5 x 1.0 cm, was detected within the wall of the urethra close to the vagino-urethral orifice. In Case 2, firm, mottled yellow, white and red tissue formed a thickening between the urethra and vagina. In Case 3, a cylindrical cream mass, 8 cm long and 3 cm in diameter, surrounded the urethra and impinged on the wall of the vagina. Histologically, glandular structures lined by a single layer of epithelial cells and a mixed granulomatous inflammatory reaction were present in the wall of the urethra of all three cases.

Animals↗
PubMed1996

Somatostatin receptor subtypes: specific expression and signaling properties.

The five cloned somatostatin (SRIF) receptors (ssts) are presumed to subserve unique biological roles by virtue of their tissue-specific expression and particular signal transduction mechanisms. However, the function of any individual sst subtype in its normal physiological milieu is not understood, because tissues and cells often express multiple ssts and, in the absence of receptor-specific SRIF analogs, the actions of individual receptors cannot be identified. To unravel the physiological role and signaling mechanism of the ssts, we have generated receptor subtype-specific antibodies and used these antibodies to determine the distribution of the receptor proteins and to identify the signal-transducing molecules with which particular sst subtypes interact.

Animals↗
PubMed1996

Determinants of research follow-up participation in an alcohol treatment outcome trial.

This study examined factors associated with research attrition in a long-term follow-up study (48 months). Researchers attempted to contact all randomized participants, not just those who completed treatment. The processes by which baseline characteristics, early treatment-research experiences, and short-term outcome affected subsequent participations were examined using logistic regression. The analyses deal primarily with refusal, the main reason for attrition. Baseline characteristics had small effects on likelihood of refusal; research engagement had some impact; but treatment participation had strong effect. Short-term outcome did not predict refusal. These findings, if generalizable, have implications for the conduct and reporting of outcome studies. By directly studying bias, rather than presuming its absence on skimpy evidence, researchers can achieve a better understanding of the strengths and limitations of outcome results.

Adult↗
PubMed1996

Health beliefs and alternative medicine: a qualitative study of breast cancer patients.

BACKGROUND AND METHODS: To explore beliefs among patients who use alternative medicine, the authors interviewed 20 female breast cancer patients for their perceptions of health, illness, and medical care. The participants had used either conventional therapies alone (conventional group, n = 11) or conventional with alternative therapies (unconventional group, n = 9). RESULTS: Beliefs about the cause of illness were similar between groups, whereas beliefs about recovery showed greater variation. In addition, the patients in the unconventional group perceived their beliefs to be recently formed and chiefly influenced by their cancer experiences, while the patients in the conventional group felt that their beliefs were "lifelong" and influenced primarily by upbringing. CONCLUSIONS: Beliefs about health and illness represent an evolving process related to changes in the way patients understand their illness over time. Discussing patients' beliefs in the clinical setting may help physicians better understand patients' choices with regard to medical care.

Adult↗