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R Bond

Publications and source records attributed to R Bond.

At least 55 records · Page 3Linked to original sources
PubMed1998

Crystal structure of farnesyl protein transferase complexed with a CaaX peptide and farnesyl diphosphate analogue.

The crystallographic structure of acetyl-Cys-Val-Ile-selenoMet-COOH and alpha-hydroxyfarnesylphosphonic acid (alphaHFP) complexed with rat farnesyl protein transferase (FPT) (space group P61, a = b = 174. 13 A, c = 69.71 A, alpha = beta = 90 degrees, gamma = 120 degrees, Rfactor = 21.8%, Rfree = 29.2%, 2.5 A resolution) is reported. In the ternary complex, the bound substrates are within van der Waals contact of each other and the FPT enzyme. alphaHFP binds in an extended conformation in the active-site cavity where positively charged side chains and solvent molecules interact with the phosphate moiety and aromatic side chains pack adjacent to the isoprenoid chain. The backbone of the bound CaaX peptide adopts an extended conformation, and the side chains interact with both FPT and alphaHFP. The cysteine sulfur of the bound peptide coordinates the active-site zinc. Overall, peptide binding and recognition appear to be dominated by side-chain interactions. Comparison of the structures of the ternary complex and unliganded FPT [Park, H., Boduluri, S., Moomaw, J., Casey, P., and Beese, L. (1997) Science 275, 1800-1804] shows that major rearrangements of several active site side chains occur upon substrate binding.

Alkyl and Aryl Transferases↗
PubMed1998

Humoral and cell-mediated responses to Malassezia pachydermatis in healthy dogs and dogs with Malassezia dermatitis.

The in vitro proliferative responses of peripheral blood mononuclear cells from seven healthy basset hounds exposed to Malassezia pachydermatis antigen (500 micrograms/ml) exceeded (P < 0.05) those of seborrhoeic basset hounds with high populations of M pachydermatis and eight Irish setters with gluten-sensitive enteropathy. The stimulation indices in the latter two groups and in eight healthy beagles were comparable. The stimulation indices of the four groups after exposure to phytohaemaglutinin did not differ significantly. The serum titres of M pachydermatis-specific IgG and IgA measured by enzyme-linked immunosorbent assays (ELISA) in 21 seborrhoeic basset hounds and 11 affected dogs of various breeds exceeded those of 14 healthy basset hounds and eight healthy beagles (P < 0.01 for IgG, P < 0.05 for IgA). Total serum IgA concentrations measured by ELISA in the affected dogs were not lower than those of healthy dogs.

Animals↗
PubMed1998

Postoperative adjuvant radiotherapy and 5-fluorouracil chemotherapy for rectal carcinoma.

Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months' duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage II or III disease received postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non-radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71% and 79%, respectively.

Adenocarcinoma↗
PubMed1996

Comparison of media and conditions of incubation for the quantitative culture of Malassezia pachydermatis from canine skin.

Fifty-five swab-wash specimens from dogs were cultured at 32 degrees C on Sabouraud's dextrose agar either with or without 1 per cent Tween 80. Ushijima's medium A and modified Dixon's and Leeming's media. The counts of Malassezia pachydermatis were not significantly different after three or seven days of incubation. Colony counts on contact plates were significantly greater after incubation for seven days on Sabouraud's dextrose (P < 0.001) and modified Dixon's agars (P < 0.05) than after three days at 26 degrees C, but not at 32 degrees C. Counts on Sabouraud's or modified Dixon's agars after incubation at 32 degrees C and 37 degrees C were not significantly different. When compared with aerobic culture, an atmosphere containing 5 to 10 per cent carbon dioxide significantly (P < 0.01) increased the frequency of isolation and colony counts on Sabouraud's dextrose agar but not on modified Dixon's agar.

Aerobiosis↗
PubMed1996

Record linkage strategies, outpatient procedures, and administrative data.

By understanding the range of approaches implicit in modern record linkage, epidemiologists and health services researchers can better decide its suitability for their needs. The authors discuss a small record linkage project, providing a sense of where mistakes were made. The research first uses existing identification numbers as a gold standard for linking hospital abstracts and physician claims to investigate whether or not coronary angiography was performed on a given individual. Even if identification numbers are not available, a successful linkage (with more than 95% of the cases matched) may be possible under some circumstances. The linkage process highlights problems with the consistent recording of coronary angiography in inpatient and outpatient hospital abstracts. Our approach should prove useful when the same procedure is recorded in more than one place on a single file and when validating a procedure (or other event) across files is important. Given the growing number of health care databases and ongoing changes in the delivery of care, record linkage often can provide quality control and expand research opportunities in a timely fashion.

Abstracting and Indexing↗
PubMed1996

Factors associated with elevated cutaneous Malassezia pachydermatis populations in dogs with pruritic skin disease.

The prevalences of breeds and concurrent diseases in a group of 40 dogs with pruritic skin disease associated with elevated cutaneous Malassezia pachydermatis populations were compared with samples of a dermatological hospital population. The ages and genders of the affected dogs were comparable to those of the dermatology population. Basset hounds, cocker spaniels and West Highland white terriers were significantly overrepresented. Concurrent diseases were diagnosed in 27 dogs, of which 15 were atopic. However, the prevalences of atopic disease, primary keratinisation defects and endocrinopathies in dogs with elevated cutaneous M pachydermatis populations were comparable to those in the dermatology population as a whole. These results indicate that certain breeds are predisposed to the development of elevated cutaneous M pachydermatis populations and that concurrent skin diseases can frequently be identified in affected dogs. However, the relationship between these concurrent diseases and abnormal M pachydermatis populations remains unclear.

Animals↗
PubMed1995

Novel tricyclic inhibitors of farnesyl protein transferase. Biochemical characterization and inhibition of Ras modification in transfected Cos cells.

Ras protooncogenes encode 21-kDa membrane-associated guanine nucleotide-binding proteins, which play a critical role in control of cellular proliferation and differentiation. Oncogenic, activated forms of Ras proteins are associated with a broad range of human cancers. The elucidation of the post-translational modifications that occur at the carboxyl terminus of Ras and the demonstration that farnesylation of Ras by farnesyl protein transferase is essential for Ras-induced cellular transformation has opened up a new and promising approach to the development of anti-Ras therapeutics. We report here a novel series of potent farnesyl protein transferase (FPT) inhibitors, represented by SCH 44342. This compound inhibits both rat brain and recombinant human FPT with an IC50 of approximately 250 nM, while it is only weakly active against rat brain geranylgeranyl protein transferase-1 (IC50 > 114 microM). FPT inhibition has been observed using both Ha-Ras protein and Ki-Ras-derived peptide substrates in two different assay formats. SCH 44342 and its analogs also inhibit farnesylation of Ras in Cos cells transiently expressing [Val12]Ha-Ras with IC50 values in the low micromolar range. At these concentrations they do not inhibit sterol biosynthesis or geranylgeranylation of protein. In addition, we observed that Cos cells undergo pronounced morphological changes upon overexpression of [Val12]activated forms of Ha-Ras containing COOH-terminal sequences allowing farnesylation (CVLS) or geranylgeranylation (CVLL) but not upon overexpression of activated Ras lacking the isoprenylated Cys (SVLS). Ras-induced morphological changes can be partially reverted with lovastatin. Importantly, SCH 44342 can block morphological changes induced by [Val12]Ha-Ras-CVLS but not [Val12]Ha-Ras-CVLL. Recently, a number of other FPT inhibitors have been reported. Most of the compounds reported to have cell-based activity are peptidomimetic analogs of the CAAX substrate. Our FPT inhibitors are novel in that although they compete with Ras protein in kinetic experiments they are entirely nonpeptidic in nature, they do not have oxidizable sulfhydryl functions, and they are active in cells at low micromolar concentrations.

Alkyl and Aryl Transferases↗
PubMed1995

Metabolic epidermal necrosis in two dogs with different underlying diseases.

Two dogs with metabolic epidermal necrosis had hyperkeratosis of the footpads accompanied by erythematous, erosive and crusting lesions affecting the muzzle, external genitalia, perineum and periocular regions. Histopathological examination of skin biopsies revealed a superficial hydropic dermatitis with marked parakeratosis. Both dogs had high plasma activities of alkaline phosphatase and alanine aminotransferase and high concentrations of glucose, and also a marked hypoaminoacidaemia. Despite these similarities, the cutaneous eruptions were associated with different underlying diseases. One dog had a pancreatic carcinoma which had metastasised widely; the primary tumour and the metastases showed glucagon immunoreactivity on immunocytochemical staining, and the dog's plasma glucagon concentration was markedly greater than that of control dogs. The other dog had diffuse hepatic disease; its plasma glucagon concentration was similar to that of control samples and cirrhosis was identified post mortem. Metabolic epidermal necrosis in dogs is a distinct cutaneous reaction pattern which may be associated with different underlying systemic diseases; however, the pathogenesis of the skin lesions remains unclear.

Alanine Transaminase↗
PubMed1995

Evaluation of a detergent scrub technique for the quantitative culture of Malassezia pachydermatis from canine skin.

A detergent scrub technique using wash fluid consisting of 0.075 M phosphate-buffered saline, pH 7.9 containing 0.1 per cent Triton X-100 was evaluated for the quantitative culture of Malassezia pachydermatis from canine skin. Preliminary studies showed that the detergents Triton X-100, Tween 40 and Tween 80 were equally able to disperse suspensions of pure cultures of M pachydermatis, but that the yeast counts were significantly reduced (P < 0.001) after suspension in saline, Triton X-100 or Tween 40 for two hours. The counts in skin washings were also reduced (P < 0.001) after suspension for three hours in 0.1 and 0.05 per cent solutions of Triton X-100. Vortexing, or manual or mechanical shaking of the samples yielded comparable counts. The correlation between the counts on diseased skin measured by using detergent scrubs and a contact plate technique was highly significant (P < 0.001). The detergent scrub technique was suitable for the quantitation of M pachydermatis on canine skin provided that the samples were processed without delay.

Animals↗
PubMed1995

Characterization of markedly lipid-dependent Malassezia pachydermatis isolates from healthy dogs.

When 244 Malassezia colonies which had been isolated from a colony of Beagle dogs using modified Dixon's agar were sub-cultured on Sabouraud's dextrose agar to determine their lipid dependence, 30 showed poor growth resembling M. furfur, whereas the remainder were typical of M. pachydermatis. Eight of the 10 poor growing isolates selected for further study formed colonies typical of M. pachydermatis after five passages on Sabouraud's dextrose agar at 4 d intervals and two continued to show poor growth. Nine isolates had enzyme profiles identical to those of typical M. pachydermatis isolates, and one resembled M. furfur. However, seven of the poor growing isolates which were karyotyped had patterns typical of M. pachydermatis. Poor growing isolates and their non-lipid-dependent 'revertants' had identical restriction fragment length polymorphism patterns and poly(GT) hybridization profiles. These observations show that some M. pachydermatis isolates grow poorly when sub-cultured onto Sabouraud's dextrose agar and may be incorrectly identified as M. furfur if further studies are not performed.

Anal Canal↗
PubMed1995

Comparison of two shampoos for treatment of Malassezia pachydermatis-associated seborrhoeic dermatitis in basset hounds.

A randomised-double-blind parallel study compared the clinical and antimicrobial efficacies of a miconazole-chlorhexidine shampoo with a selenium sulphide shampoo for the treatment of seborrhoeic dermatitis associated with Malassezia pachydermatis in 33 basset hounds. All 16 miconazole-chlorhexidine treated hounds and 11 of 17 selenium sulphide treated hounds improved when shampooed at three-day intervals for three weeks. The miconazole-chlorhexidine treated hounds showed significantly greater reductions in pruritus (P < 0.01), erythema (P < 0.001), exudation (P < 0.01) and overall severity (P < 0.001), and in counts of M pachydermatis (P < 0.001), total bacteria (P < 0.001) and coagulase-positive staphylococci (P < 0.001), when compared to the selenium sulphide treated group. Improvements in scaling and coat condition did not vary significantly between the two groups. These results indicate that seborrhoeic dermatitis in basset hounds is often associated with elevated cutaneous populations of M pachydermatis and bacteria, and that the miconazole-chlorhexidine shampoo is more effective than the selenium sulphide product for the treatment for this disease.

Animals↗
PubMed1995

Canine eosinophilic folliculitis and furunculosis in three cases.

The historical, clinical and histopathological features of three dogs with eosinophilic folliculitis and furunculosis are described. The disease was characterised by the rapid development of pruritic, papular, pustular and ulcerative lesions on the dorsum of the muzzle. Skin lesions were confined to the face in two cases. The third dog had more generalised pustular lesions. Skin biopsy specimens showed marked eosinophil infiltration particularly centred on pilosebaceous units. Dermal collagen necrosis was evident in two cases. Similar facial lesions have previously been described as 'nasal pyoderma'. The three dogs failed to respond to initial antibacterial therapy but showed a rapid clinical response when prednisolone was given orally at doses ranging from 1 to 2.2 mg/kg, in addition to the antibacterial therapy, suggesting that glucocorticoids are indicated for the treatment of eosinophilic folliculitis and furunculosis. The aetiology of the disease was not determined.

Administration, Oral↗