Search PubMed⌕ Search

Biomedical subjects

S Freeman

Publications and source records attributed to S Freeman.

At least 55 records · Page 3Linked to original sources
PubMed2000

Effect of high-dose cisplatin on auditory brainstem responses and otoacoustic emissions in laboratory animals.

OBJECTIVE: The role of transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE) as early indicators of cisplatin-induced ototoxicity in three different rodent species--the guinea pig. the albino rat, and the fat sand rat (Psammomys obesus)--was investigated. In addition, an attempt was made to determine which of the three rodent species is most susceptible to cisplatin-induced ototoxicity as measured by auditory brainstem responses (ABR), BACKGROUND: There have been numerous clinical and experimental reports on cisplatin-induced ototoxicity, but to the authors' best knowledge, there has been no comparative report on the short-term effects of cisplatin on OAE measured with commercially available equipment between different rodent species. METHODS: Cisplatin was systemically administered as a single high dose (12 mg/kg intraperitoneally) to all three species, and the ototoxic effects were measured before and 3 days after the injection of cisplatin in the same animals, using ABR, TEOAE, and DPOAE. RESULTS: The ABR thresholds were significantly elevated in the guinea pigs and the albino rats but not in the sand rats. Significant depression of TEOAE energy and DPOAE amplitude occurred only in the guinea pigs. The depression of the DPOAE was greater than that of the TEOAE. The guinea pigs showed the greatest degree of ototoxicity (depression of ABR and OAE). CONCLUSIONS: Among the three rodent species, the guinea pig has the potential to be used as a sensitive animal model in studies of cisplatin ototoxicity. The study also showed that the recordings of TEOAE and DPOAE, in addition to ABR, are sensitive techniques for the assessment of cisplatin-induced ototoxicity.

Animals↗
PubMed1999

Species and strain comparisons in the macromolecular binding of extremely low doses of [14C]benzene in rodents, using accelerator mass spectrometry.

The kinetics of macromolecular binding of a 5 micrograms/kg body wt dose of [14C]benzene was studied over 48 h in B6C3F1, DBA/2, and C57BL/6 mice and Fischer rats to determine if adduct levels reflect known differences in metabolic capacity, genotoxicity, and carcinogenic potency. Previous studies have suggested that differences in benzene toxicity among strains result from differences in metabolism. Rats and mice were administered [14C]benzene (i.p.), followed by removal of liver and bone marrow at time intervals up to 48 h postexposure. Protein and DNA were isolated and analyzed by accelerator mass spectrometry. Area under the curves for protein and DNA adducts in bone marrow were greatest in B6C3F1 mouse > DBA/2 mouse > C57BL/6 mouse > Fischer rat. These data are consistent with the hypothesis that metabolic capacity contributes to the difference in benzene's carcinogenicity among species. Additionally, these data suggest that target organ adduct levels correlate with tumorigenicity and thus may be indicative of an individuals risk.

Animals↗
PubMed1999

Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein.

Retinol-binding protein (RBP) is the sole specific transport protein for retinol (vitamin A) in the circulation, and its single known function is to deliver retinol to tissues. Within tissues, retinol is activated to retinoic acid, which binds to nuclear receptors to regulate transcription of >300 diverse target genes. In the eye, retinol is also activated to 11-cis-retinal, the visual chromophore. We generated RBP knockout mice (RBP(-/-)) by gene targeting. These mice have several phenotypes. Although viable and fertile, they have reduced blood retinol levels and markedly impaired retinal function during the first months of life. The impairment is not due to developmental retinal defect. Given a vitamin A-sufficient diet, the RBP(-/-) mice acquire normal vision by 5 months of age even though blood retinol levels remain low. Deprived of dietary vitamin A, vision remains abnormal and blood retinol declines to undetectable levels. Another striking phenotype of the mutant mice is their abnormal retinol metabolism. The RBP(-/-) mice can acquire hepatic retinol stores, but these cannot be mobilized. Thus, their vitamin A status is extremely tenuous and dependent on a regular vitamin A intake. Unlike wild-type mice, serum retinol levels in adult RBP(-/-) animals become undetectable after only a week on a vitamin A-deficient diet and their retinal function rapidly deteriorates. Thus RBP is needed for normal vision in young animals and for retinol mobilization in times of insufficient dietary intake, but is otherwise dispensable for the delivery of retinol to tissues.

Age Factors↗
PubMed1999

Mycobacterium tuberculosis CDC1551 induces a more vigorous host response in vivo and in vitro, but is not more virulent than other clinical isolates.

Mycobacterium tuberculosis CDC1551, a clinical isolate reported to be hypervirulent and to grow faster than other isolates, was compared with two other clinical isolates (HN60 and HN878) and two laboratory strains (H37Rv and Erdman). The initial (1-14 days) growth of CDC1551, HN60, HN878, and H37Rv was similar in the lungs of aerosol-infected mice, but growth of Erdman was slower. Thereafter, the growth rate of CDC1551 decreased relative to the other strains which continued to grow at comparable rates up to day 21. In the lungs of CDC1551-infected mice, small well-organized granulomas with high levels of TNF-alpha, IL-6, IL-10, IL-12, and IFN-gamma mRNA were apparent sooner than in lungs of mice infected with the other strains. CDC1551-infected mice survived significantly longer. These findings were confirmed in vitro. The growth rates of H37Rv and CDC1551 in human monocytes were the same, but higher levels of TNF-alpha, IL-10, IL-6, and IL-12 were induced in monocytes after infection with CDC1551 or by exposure of monocytes to lipid fractions from CDC1551. CD14 expression on the surface of the monocytes was up-regulated to a greater extent by exposure to the lipids of CDC1551. Thus, CDC1551 is not more virulent than other M. tuberculosis isolates in terms of growth in vivo and in vitro, but it induces a more rapid and robust host response.

Aerosols↗
PubMed1999

Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31.

Recent studies have shown that, in addition to its role as an adhesion receptor, platelet endothelial cell adhesion molecule 1/CD31 becomes phosphorylated on tyrosine residues Y663 and Y686 and associates with protein tyrosine phosphatases SHP-1 and SHP-2. In this study, we screened for additional proteins which associate with phosphorylated platelet endothelial cell adhesion molecule 1, using surface plasmon resonance. We found that, besides SHP-1 and SHP-2, platelet endothelial cell adhesion molecule 1 binds the cytoplasmic signalling proteins SHIP and PLC-gamma1 via their Src homology 2 domains. Using two phosphopeptides, NSDVQpY663TEVQV and DTETVpY686SEVRK, we demonstrate differential binding of SHP-1, SHP-2, SHIP and PLC-gamma1. All four cytoplasmic signalling proteins directly associate with cellular platelet endothelial cell adhesion molecule 1, immunoprecipitated from pervanadate-stimulated THP-1 cells. These results suggest that overlapping immunoreceptor tyrosine-based inhibition motif/immunoreceptor tyrosine-based activation motif-like motifs within platelet endothelial cell adhesion molecule 1 mediate differential interactions between the Src homology 2 containing signalling proteins SHP-1, SHP-2, SHIP and PLC-gamma1.

Amino Acid Sequence↗
PubMed1999

Effects of cholinergic blockers on auditory brain-stem evoked potentials in rats.

The pharmacology of auditory brain-stem evoked potentials (ABEP) pathways is poorly understood. There are anecdotal reports on the involvement of various neurotransmitters but they were not investigated systematically. The aim of this study was to investigate the effects on ABEP of muscarinic and nicotinic blockers, administered into the cerebral ventricles. Atropine sulfate, d-Tubocurarine and saline were injected stereotactically into the lateral cerebral ventricle of anesthetized male rats. Auditory clicks were given at a rate of 20 s(-1). ABEP recording was performed before and 30 min after injection. Pre- and post-injection peak latencies and peak-to-peak amplitudes of positive waves were compared for each animal. Atropine reduced the amplitudes of waves P1, P3 and P4 and increased mildly the brain stem transmission time. d-Tubocurarine reduced the amplitudes of P1 and P4 with no significant effect on the peak latencies. Saline injection had no effect on any of the parameters. These results show that both cholinergic systems are involved in ABEP generation or transmission. Mechanism of action could be either direct inhibition of afferent pathways or indirect effect, via modulating efferent pathways.

Animals↗
PubMed1999

Development of short latency vestibular evoked potentials in the neonatal rat.

The development of short latency vestibular evoked potentials (VsEPs) was investigated in the neonatal rat. Using the appropriate stimulus (linear or angular acceleration impulses) and head orientation, responses elicited in various vestibular end-organs (utricle: x-VsEP; saccule: z-VsEP; lateral semi-circular canal: a-VsEP) were measured in rat pups at various ages between post-natal days (PND) 5 and 30, and compared to those recorded from adult animals. It was found that the VsEPs initially appeared on PND 6 (x-VsEPs and z-VsEPs) or 7 (a-VsEPs), and that by PND 8 the three responses could be recorded in all animals. The first wave of the responses, generated in the primary sensory nerve and reflecting end-organ activity, reached adult latencies and amplitudes by PND 10, showing rapid maturity of the responses. Auditory responses, on the other hand, develop at a later stage (from PND 11). The possible mechanisms involved in this differential maturation between vestibular and auditory activity are discussed.

Acceleration↗
PubMed1999

Inositol polyphosphate-mediated iron transport in Pseudomonas aeruginosa.

It has previously been shown that myo-inositol hexakisphosphate (myo-InsP6) mediates iron transport into Pseudomonas aeruginosa and overcomes iron-dependent growth inhibition. In this study, the iron transport properties of myo-inositol trisphosphate and tetrakisphosphate regio-isomers were studied. Pseudomonas aeruginosa accumulated iron (III) at similar rates whether complexed with myo-Ins(1,2,3)P3 or myo-InsP6. Iron accumulation from other compounds, notably D/L myo-Ins(1,2,4,5)P4 and another inositol trisphosphate regio-isomer, D-myo-Ins(1,4,5)P3, was dramatically increased. Iron transport profiles from myo-InsP6 into mutants lacking the outer membrane porins oprF, oprD and oprP were similar to the wild-type, indicating that these porins are not involved in the transport process. The rates of reduction of iron (III) to iron (II) complexed to any of the compounds by a Ps. aeruginosa cell lysate were similar, suggesting that a reductive mechanism is not the rate-determining step.

Biological Transport↗
PubMed1999

Cutaneous allergic reaction to intramuscular vitamin K1.

A 40-year-old woman with no pre-existing hepatic disease developed a cutaneous allergic reaction to intramuscular vitamin K1. She received this medication prophylactically prior to surgery, developed severe localized, and subsequently generalized, dermatitis, beginning 5 days after administration of the Konakion Cremophor-EL form of vitamin K1 by intramuscular injection at four sites on her thighs. Investigation by patch and intradermal testing revealed delayed-type hypersensitivity to Konakion Cremophor-EL, Konakion Mixed Micelles and pure vitamin K1, but not Cremophor-EL vehicle alone. This case is unusual because the patient was also shown to be patch test positive to vitamin K3 sodium bisulfite.

Adult↗
PubMed1999

Renal function in chronically catheterized conscious diabetic rats using constant and servo-controlled infusion.

1. Infusion experiments were performed on chronically catheterized conscious rats to assess kidney function before and after the induction of diabetes mellitus with streptozotocin. 2. Two infusion regimens were used, a conventional constant-infusion protocol and a novel computer-driven, servo-controlled fluid replacement technique. The latter enables body fluid status to be maintained throughout a study occasion by servo-controlled replacement of spontaneous urinary fluid losses. 3. The chronically catheterized conscious rat infused using a servo-controlled system appears to be the optimum model for a study of diabetic renal function. The conscious preparation circumvents problems associated with anaesthesia and acute surgery. The servo-controlled infusion protocol maintains the altered fluid status of the diabetic condition. Both hyperfiltration and polyuria, characteristics of human diabetes often absent in anaesthetized and/or constantly infused diabetic rats, were seen in all conscious servo-controlled diabetic animals. 4. The new regimen enables a more accurate assessment of renal function in experimental diabetes than with previous protocols. It should prove useful in future studies, particularly those assessing the role of anti-diabetic drugs on the kidney.

Animals↗
PubMed1999

Cheilitis: analysis of 75 cases referred to a contact dermatitis clinic.

BACKGROUND: Cheilitis is a common problem, the cause of which is often obscure. OBJECTIVE: Data on 75 cases of recalcitrant cheilitis were analyzed. These had been referred to a tertiary care center. METHODS: Each of the 75 patients had undergone a detailed history, physical examination, and patch tests. RESULTS: Of the patients, 53 were female (67%), and the age range was 9 to 79 years. Of the cases, 36% included irritant contact dermatitis (ICD), 25% included allergic contact dermatitis (ACD), 19% were attributed to atopic eczema, and in 9% the dermatitis was of unknown cause. Nine percent were noneczematous. The materials causing ACD were medicaments applied to the lips, lipstick ingredients, sunscreen agents, toothpaste ingredients, colophony in dental floss and toothpicks, nail varnish, cosmetics, and nickel in the mouthpiece of a flute. CONCLUSION: The most common cause of cheilitis was irritation, frequently caused by liplicking. About one quarter was caused by ACD. Medicaments, lipsticks, sunscreens, and toothpaste were the most common allergens. Atopic eczema is a commonly overlooked cause of cheilitis. However, there is a troublesome group of patients, 9% in this series, who are often severely affected, but the cause of their cheilitis remains obscure.

Adolescent↗
PubMed1999

Effect of white noise "masking" on vestibular evoked potentials recorded using different stimulus modalities.

Short latency vestibular evoked potentials (VsEPs) to linear acceleration impulses (L-VsEPs) are initiated in the otolith organs (saccule and utricle). Some of the saccule afferents have been reported to respond not only to linear acceleration, but also to high intensity acoustic stimuli. If so, the L-VsEP recorded from the saccule (elicited with the stimulus orientated relative to the head so as to optimally activate the saccule, i.e. stimulus in the vertical plane, Z-VsEP) should be reduced during high intensity broad band noise (BBN) "masking". Conversely, the utricular afferents have been reported to be less auditory-sensitive. Therefore, an L-VsEP which is mainly utricular in origin (stimulus in the horizontal plane, X-VsEP) should be less affected by this noise "masking". This was investigated in rats by recording X-VsEPs and Z-VsEPs and angular VsEPs (A-VsEPs), originating in the lateral semi-circular canals, before, during and after exposure to short duration, high intensity (113 dB SPL) BBN. This intensity completely masked auditory nerve evoked responses. The Z-VsEP did appear to be slightly more affected by the noise "masking" than the X-VsEP, implying the presence of more auditory-sensitive elements in the saccule. The A-VsEP was also affected by the BBN. The overall effect was relatively small (on average, 10-25% depression of the first wave of the different VsEPs). The responses showed recovery 5 min later.

Animals↗
PubMed1999

Biochemical analysis of plant protection afforded by a nonpathogenic endophytic mutant of colletotrichum magna

A nonpathogenic mutant of Colletotrichum magna (path-1) was previously shown to protect watermelon (Citrullus lanatus) and cucumber (Cucumis sativus) seedlings from anthracnose disease elicited by wild-type C. magna. Disease protection was observed in stems of path-1-colonized cucurbits but not in cotyledons, indicating that path-1 conferred tissue-specific and/or localized protection. Plant biochemical indicators of a localized and systemic (peroxidase, phenylalanine ammonia-lyase, lignin, and salicylic acid) "plant-defense" response were investigated in anthracnose-resistant and -susceptible cultivars of cucurbit seedlings exposed to four treatments: (1) water (control), (2) path-1 conidia, (3) wild-type conidia, and (4) challenge conditions (inoculation into path-1 conidia for 48 h and then exposure to wild-type conidia). Collectively, these analyses indicated that disease protection in path-1-colonized plants was correlated with the ability of these plants to mount a defense response more rapidly and to equal or greater levels than plants exposed to wild-type C. magna alone. Watermelon plants colonized with path-1 were also protected against disease caused by Colletotrichum orbiculare and Fusarium oxysporum. A model based on the kinetics of plant-defense activation is presented to explain the mechanism of path-1-conferred disease protection.

Journal Article↗
PubMed1999

Unclassified endogenous eczema.

Patients with intractable eczema are often referred for patch testing to exclude contact dermatitis. If this is excluded, then a diagnosis of endogenous eczema is made. At our clinic, we find a sizeable proportion of these patients do not fit any of the known patterns of endogenous eczema. These patients are given the diagnosis of unclassified endogenous eczema and make up 8% of the patients seen at our Occupational and Contact Dermatitis Clinic. There is little information available on this group of patients, with no mention of this problem in the recent dermatological literature. Since March 1996, we have further investigated these patients, to develop some understanding of this category. 12 of 34 patients reviewed over this period had an elevated IgE level above 100 IU/ ml. Thus, despite no past history or family history of eczema, asthma or hayfever, at least 1/3 of these patients are probably suffering from atypical, late onset atopic dermatitis. Patients were later contacted by telephone (average 2 years) to assess the natural history of this condition. In 20 of the 31 patients contacted, their eczema had either improved or resolved. We think that this important category of eczema needs to be recognized and further investigated.

Adolescent↗
PubMed1999

Leukoderma following occupational allergic contact dermatitis.

We describe 2 cases of occupational allergic contact dermatitis followed by leukoderma. The 1st case was a 49-year-old wood machinist who developed leukoderma in areas of contact dermatitis involving his lips, neck, hands and forearms and was found to be allergic to colophony and pine sawdust on patch testing. The 2nd case involved a 44-year-old man who worked as an epoxy applicator in a ceramics factory. He developed depigmentation in areas of contact dermatitis involving his face, hands, forearms, back, thighs and legs and was found on patch testing to be allergic to epoxy resin. The appearance of contact leukoderma may be indistinguishable from idiopathic vitiligo. However the prognosis for repigmentation may be better in contact leukoderma than in idiopathic vitiligo.

Adult↗
PubMed1999

Development of inner ear (cochlear and vestibular) function in the fetus-neonate.

The development of function in the various receptors in the inner ear was studied in the neonatal rat, which is altricious with respect to hearing, using short latency evoked potentials, both auditory (ABR) and vestibular (VsEP). It was found that VsEPs could be recorded from all the vestibular end-organs by post natal day (PND) 8, whilst ABR could only be recorded from all animals on PND 14, showing the earlier onset of vestibular function in the inner ear. These results are discussed with relation to onset of inner ear function in the human fetus.

Animals↗