Effect on herd health and productivity of controlling tsetse and trypanosomosis by applying deltamethrin to cattle

A large cattle ranch was established in 1954 in a heavily tsetse infested part of north-east Tanzania. Trypanosomosis was controlled for 30 years by prophylactic drugs but in 1988 drug resistance seemed to be developing as cases of trypanosomosis were being confirmed 4 or 5 weeks after treatment with isometamidium chloride (Samorin). Herd health had deteriorated and productivity was uneconomically low. In order to control the tsetse population the 8,000 cattle, grazing over 250 km2, were regularly dipped in the synthetic pyrethroid deltamethrin (Decatix Cattle Dip and Spray formulation). Within a year the tsetse population, as monitored by traps, had decreased by more than 90%. Disease mortality decreased by 66% and a range of productivity measures such as calving percentages and weaning weights were raised to levels above those prevailing before the decline in herd health.     

Differential sensitivity of membrane-associated pyrophosphatases to inhibition by diphosphonates and fluoride delineates two classes of enzyme

The participation of GABAergic mechanisms in the regulation of circadian rhythmicity by the suprachiasmatic nuclei (SCN) has been suggested from different lines of evidence. Little is known, however, whether GABA synthesis, release, uptake or content within the SCN may show a circadian pattern. The present results show that the activity of the GABAergic system within the SCN region of the rat exhibits circadian rhythmicity, which is manifested by correlative changes of the GABA content and the glutamic acid decarboxylase activity under the light/dark cycle, and by changes in the GABA content in animals kept under constant darkness.     

Initial response and subsequent course of Crohn's disease treated with elemental diet or prednisolone

Elemental diet is as effective as corticosteroids in the treatment of previously untreated Crohn's disease. It is unclear whether a poor nutritional state is a prerequisite for efficacy of elemental diet, whether previously treated patients respond as well, or how duration of remission using elemental diet compares with corticosteroid induced remission. Forty two patients with active Crohn's disease were stratified for nutritional state and randomised to receive Vivonex TEN 2.1 l/day for four weeks, or 0.75 mg prednisolone/kg/day for two weeks and subsequent reducing doses. Nine of 22 (41%) patients assigned to nutritional treatment were intolerant of the diet. Thirty patients completed four weeks treatment. Disease activity decreased on elemental diet from mean (SEM) 4.8 (0.9) to 1.7 (0.6), p < 0.05, and on prednisolone from 5.3 (0.5) to 1.9 (0.6), p < 0.05. For each treatment, nourished and malnourished patients responded similarly. Patients with longstanding disease responded as well as newly diagnosed patients. The probability of maintaining remission at six months was 0.67 after prednisolone, 0.28 after elemental diet, and at one year was 0.35 after prednisolone and 0.09 after elemental diet, p < 0.05. When tolerated, elemental diet is as effective in the short term as prednisolone in newly and previously diagnosed Crohn's disease, and its benefit is independent of nutritional state. The subsequent relapse rate after elemental diet induced remission, however, is greater than after treatment with prednisolone.     

Magnetic resonance imaging and invasive evaluation of development of heart failure in transgenic mice with myocardial expression of tumor necrosis factor-alpha

The intestine is a large endocrine organ, but the dependence of colon cancer on hormones remains unknown. We show here that neurotensin, a paracrine/endocrine peptide in the gut, and the neurotensin receptor antagonist SR 48692 control colon cancer cell growth in vitro and in vivo by interacting with receptors that are ectopically expressed in colon cancers. In cell culture, neurotensin stimulates the growth of human colon cancer cell lines (SW480, SW620, HT29, HCT116 and Cl.19A) expressing the neurotensin receptor NTR1 but does not change the growth of Caco2 cells, which do not express NTR1. In SW480 cells, neurotensin is active in the 10(-10) to 10(-6) M concentration range (ED50 = 0.47 nM) while the neurotensin fragment (I-II) is inactive. Neurotensin also enhances the cellular cloning efficiency of SW480 cells in soft agar by inducing a 50% increase of colony formation. This effect is blocked by SR 48692, which alone does not alter colony formation. Subcutaneous delivery of neurotensin (0.54 micromol/kg every 24 hr) by osmotic pumps to nude mice that have been xenografted with SW480 cells results in a significant increase of tumor volume, i.e., up to 255% of control at day 20 of treatment. SR 48692 administered alone (1.7 micromol/kg every 24 hr) by daily i.p. injections reduces the development of tumors formed by xenografting SW480 cells in nude mice. A significant mean reduction of tumor volume of 38% is observed during the 22-day period of treatment. SR 48692 alone is also active at reducing tumor volume after xenografting HCT116 cells in nude mice. Our results support the notion that colon cancer growth may be dependent on blood-borne neurotensin and suggest that non-peptide neurotensin antagonists, such as SR 48692, may be useful for the development of novel therapeutic strategies of colon cancer.     

Purification and properties of NADH-dependent 5, 10-methylenetetrahydrofolate reductase (MetF) from Escherichia coli

A K-12 strain of Escherichia coli that overproduces methylenetetrahydrofolate reductase (MetF) has been constructed, and the enzyme has been purified to apparent homogeneity. A plasmid specifying MetF with six histidine residues added to the C terminus has been used to purify histidine-tagged MetF to homogeneity in a single step by affinity chromatography on nickel-agarose, yielding a preparation with specific activity comparable to that of the unmodified enzyme. The native protein comprises four identical 33-kDa subunits, each of which contains a molecule of noncovalently bound flavin adenine dinucleotide (FAD). No additional cofactors or metals have been detected. The purified enzyme catalyzes the reduction of methylenetetrahydrofolate to methyltetrahydrofolate, using NADH as the reductant. Kinetic parameters have been determined at 15 degreesC and pH 7.2 in a stopped-flow spectrophotometer; the Km for NADH is 13 microM, the Km for CH2-H4folate is 0.8 microM, and the turnover number under Vmax conditions estimated for the reaction is 1,800 mol of NADH oxidized min-1 (mol of enzyme-bound FAD)-1. NADPH also serves as a reductant, but exhibits a much higher Km. MetF also catalyzes the oxidation of methyltetrahydrofolate to methylenetetrahydrofolate in the presence of menadione, which serves as an electron acceptor. The properties of MetF from E. coli differ from those of the ferredoxin-dependent methylenetetrahydrofolate reductase isolated from the homoacetogen Clostridium formicoaceticum and more closely resemble those of the NADH-dependent enzyme from Peptostreptococcus productus and the NADPH-dependent enzymes from eukaryotes.     

Emmetropization in the rhesus monkey (Macaca mulatta): birth to young adulthood

PURPOSE: To provide baseline measurements on the postnatal changes in refractive error, corneal curvature, and axial elongation of the eyes of normal monkeys. Little is known about the course of normal eye growth from birth to adolescence, particularly how refractive parameters co-vary during development. In animal models of ametropia, usually one eye is manipulated and the fellow eye serves as a control. However, given individual differences, and without baseline data, it is impossible to determine whether either eye develops normally. METHODS: Measurements were obtained on 237 rhesus monkeys, whose ages ranged from birth to 5 years. Examinations included cycloplegic refraction by retinoscopy, keratometry measurements, and A-scan ultrasound measurements of axial length. The time course of development was evaluated using a growth curve analysis appropriate for a mixture of cross-sectional and longitudinal data. RESULTS: At birth, all three parameters were normally distributed and only weakly correlated. Monkeys had +7 D (SD=2.3 D) of hyperopia, corneal power of 58 D (SD=1 D), and axial length of 13.2 mm (SD=0.4 mm). Refractive error ranged from +0.5 D to +14.5 D, with a mean difference between the two eyes of 0.5 D. Corneal curvature ranged from 61 D to 54 D, with a mean difference between the two eyes of 0.8 D. Axial length ranged from 12.0 mm to 14.2 mm, with a mean difference between the two eyes of 0.1 mm. Although the degree of hyperopia achieved asymptote, of + 2 D, shortly after 1 year of age, corneal curvature and axial length did not achieve asymptote until nearly 5 years of age. By this time, refractive error had declined by 5 D, corneal curvature had declined by 7 D, and axial length had increased by 6 mm. CONCLUSIONS: The magnitude of the individual differences that can occur in a small sample of experimental subjects is large enough to necessitate reference to age norms derived from a large population. Our results provide a baseline for studies of normal and abnormal eye growth and ametropia in primates. Our results also led to the confirmation of a set of "rules" that have been offered as an explanation of how these three parameters interact during emmetropization.     

A comparison between radioligand and immunohistochemical assay of hormone receptors in primary breast cancer

The detection of oestrogen and progesterone receptor (ER and PgR) levels in human breast carcinoma has traditionally been performed using a biochemical radioligand binding method. This method has several disadvantages including the requirement for generous tissue samples, the production of radioactive waste products and the inability to exclude non-malignant cellular material from the assay process. An alternative method for detecting hormone receptors is available with the use of a monoclonal antibody specific for the ER or PgR receptor using immunocytochemical assay (ER-ICA or PgR-ICA). Although designed for use on frozen section material, with modifications this method can be used on paraffin sections of routinely fixed and processed tissue, on archival material and on very small specimens. Further, an objective assessment or scoring of staining intensity is possible using computerized video-image analysis. Forty-three cases of primary breast carcinoma, treated from 1989 to 1991 at Goulburn Valley Base Hospital, Shepparton were assessed for ER and PgR content using both the radioligand method and immunohistochemistry with video-image analysis, and the results were compared. Of the 43 cases, ER-ICA and ER had a concordance of 81% (P < 0.001, r = 0.58) and in 39 cases, PgR and PgR-ICA had a concordance of 87% (P < 0.001, r = 0.54). Because the sample for radioligand assay is of uncertain composition and the immunohistochemical stain can be scored specifically for malignant epithelium, a degree of discordance is thought to be mostly attributable to the limitations of the radioligand assay.     

Living-related organ donation: the donor's dilemma

New procedures for segmented organ transplantation of the lung and liver have again brought to public attention the issue of live organ donation. To provide a context for understanding the dilemmas faced by potential donors, the body of literature over the last 40 years regarding living-related organ donation with kidneys was reviewed. Results indicated that while psychological side effects have been reported including depression and family conflict these risks are generally under-emphasized. Risk factors for negative psychological consequences include high age, lack of social support, and organ rejection in the recipient. Instantaneous decision-making in favor of donation is generally described. However, researchers have neglected to consider social desirability factors when assessing donor motives. Furthermore, lack of awareness has been shown concerning the coercive processes involved in moral decision-making. Health professionals should be aware that merely raising the issue of live organ donation may instigate powerful psychological processes beyond the potential donor's voluntary control and leave little room for refusal without psychological cost. Implications for treatment are discussed with these circumstances in mind.     

Nitric oxide localized to spinal cords of mice with experimental allergic encephalomyelitis: an electron paramagnetic resonance study

Experimental allergic encephalomyelitis (EAE) is a demyelinating autoimmune disorder that can be induced in susceptible mice by T lymphocytes sensitized to central nervous system (CNS) myelin components and is a prime animal model for the human CNS demyelinating disorder, multiple sclerosis (MS). Although CNS inflammation in which T lymphocytes and activated macrophages are the predominant cell types is observed in mice with EAE and in humans with MS, the exact mechanisms underlying the CNS damage and demyelination are not understood. Nitric oxide (NO), a gaseous free radical, has recently been shown to be a cytolytic product of activated macrophages. Using electron paramagnetic resonance spectroscopy, the nitric oxide free radical complexed with iron-sulfur proteins has been identified in affected spinal cords of mice with EAE, concurrent with the diminution of iron-sulfur proteins. These results indicate NO may play a role in the disease process of EAE, and perhaps MS.