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Biomedical subjects

A Griffin

Publications and source records attributed to A Griffin.

At least 19 recordsLinked to original sources
PubMed2003

The use of immunohistochemistry in distinguishing reactive from neoplastic mesothelium. A novel use for desmin and comparative evaluation with epithelial membrane antigen, p53, platelet-derived growth factor-receptor, P-glycoprotein and Bcl-2.

AIMS: To evaluate the expression of the intermediate filament desmin in reactive mesothelium and malignant mesothelioma and to compare its utility with five other previously reported immunomarkers claimed to be of use in distinguishing reactive from neoplastic mesothelium. METHODS AND RESULTS: Sixty cases of malignant pleural mesothelioma and 40 cases of reactive mesothelial hyperplasia formed the study group. Cases were immunohistochemically stained with desmin, epithelial membrane antigen (EMA), p53, Bcl-2, P-glycoprotein and platelet-derived growth factor receptor (PDGF-R) beta-chain by the avidin-biotin complex method. The cohort of malignant pleural mesotheliomas were immunoreactive to desmin, EMA and p53 in 6/60 (10%), 48/60 (80%) and 27/60 (45%), respectively. In comparison, the cohort of reactive mesothelial hyperplasias were immunoreactive to desmin, EMA and p53 in 34/40 (85%), 8/40 (20%) and 0/40 (0%), respectively. In a smaller cohort (n = 15) of malignant pleural mesotheliomas, Bcl-2, P-glycoprotein and PDGF-R beta-chain were expressed in 0/15 (0%), 2/15 (13%) and 15/15 (100%), respectively. In a small cohort (n = 15) of reactive mesothelial hyperplasias, Bcl-2, P-glycoprotein and PDGF-R beta-chain were immunoreactive in 0/15 (0%), 0/15 (0%) and 6/15 (40%), respectively. CONCLUSIONS: Desmin and EMA appear to be the most useful markers in distinguishing benign from malignant mesothelial proliferations. Desmin appears to be preferentially expressed in reactive mesothelium and EMA appears to be preferentially expressed in neoplastic mesothelium. The complementary use of both markers is advocated in ascertaining the nature of mesothelial proliferations. Immunohistochemical detection of mutated p53 oncoprotein appeared to be of less utility in this study on account of the low marker sensitivity for malignant mesothelioma. However, p53 antibody may be of use as a second-line marker of neoplastic mesothelium within a standard immunohistochemical panel of antibodies. In this study, Bcl-2, P-glycoprotein and PDGF-R beta-chain appear to be of no use in distinguishing reactive from neoplastic mesothelium, although more formal evaluation of these markers is required.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

BCS-BEC crossover in a gas of Fermi atoms with a Feshbach resonance.

We discuss the BCS-BEC crossover in a degenerate Fermi gas of two hyperfine states interacting close to a Feshbach resonance. We show that, by including fluctuation contributions to the free energy similar to that considered by Nozières and Schmitt-Rink, the character of the superfluid phase transition continuously changes from the BCS-type to the BEC-type, as the threshold of the quasimolecular band is lowered. In the BEC regime, the superfluid phase transition is interpreted in terms of molecules associated with both the Feshbach resonance and Cooper pairing.

Journal Article↗
PubMed2002

Dynamical instability of a condensate induced by a rotating thermal gas.

We study surface modes of the condensate in the presence of a rotating thermal cloud in an axisymmetric trap. By considering collisions that transfer atoms between the condensate and the noncondensate, we find that m>0 modes, which rotate in the same sense as the thermal cloud, damp less strongly than m<0 modes, where m is the polarity of the excitation. We show that above a critical angular rotation frequency, equivalent to the Landau stability criterion, m>0 modes become dynamically unstable, leading to the possibility of vortex nucleation. We also generalize our stability analysis to treat the case where the stationary state of the condensate already possesses a single vortex.

Journal Article↗
PubMed2001

Non-syndromic progressive hearing loss DFNA38 is caused by heterozygous missense mutation in the Wolfram syndrome gene WFS1.

Dominantly inherited progressive hearing loss DFNA38 is caused by heterozygosity for a novel mutation in WFS1, the gene for recessively inherited Wolfram syndrome. Wolfram syndrome is defined by juvenile diabetes mellitus and optic atrophy and may include progressive hearing loss and other neurological symptoms. Heterozygotes for other Wolfram syndrome mutations generally have normal hearing. Dominant deafness defined by DFNA38 is more severe than deafness of Wolfram syndrome patients and lacks any syndromic features. In a six-generation kindred from Newfoundland, Canada, WFS1 Ala716Thr (2146 G-->A) was shared by all deaf members of the family and was specific to deaf individuals. The causal relationship between this missense mutation and deafness was supported by two observations based on haplotype and mutation analysis of the kindred. First, a relative homozygous for the mutation was diagnosed at age 3 years with insulin-dependent diabetes mellitus, the central feature of Wolfram syndrome. Second, two relatives with normal hearing had an identical haplotype to that defining DFNA38, with the exception of the base pair at position 2146. Other rare variants of WFS1 co-inherited with deafness in the family could be excluded as disease-causing mutations on the basis of this hearing-associated haplotype. The possibility that 'mild' mutations in WFS1 might be a cause of non-syndromic deafness in the general population should be explored.

Amino Acid Sequence↗
PubMed2001

Cooperation, control, and concession in meerkat groups.

"Limited control" models of reproductive skew in cooperative societies suggest that the frequency of breeding by subordinates is determined by the outcome of power struggles with dominants. In contrast, "optimal skew" models suggest that dominants have full control of subordinate reproduction and allow subordinates to breed only when this serves to retain subordinates' assistance with rearing dominants' own litters. The results of our 7-year field study of cooperative meerkats, Suricata suricatta, support the predictions of limited control models and provide no indication that dominant females grant reproductive concessions to subordinates to retain their assistance with future breeding attempts.

Africa, Southern↗
PubMed2001

Pathologic fractures of the proximal femur secondary to benign bone tumors.

Pathologic fractures of the proximal femur secondary to benign bone tumors often are difficult to treat because of specific anatomic features of this region and the aggressiveness of the tumors. Between 1986 and 1996, 11 patients presented with a pathologic fracture of the proximal femur secondary to a benign bone tumor. All were treated with a uniform approach consisting of biopsy, intralesional curettage, high-speed burring, and reconstruction using morselized allograft, autograft, and a fixed-angle implant. The average followup was 4 years 3 months (range, 24-114 months). One patient was lost to followup. All fractures healed, and there were no local recurrences and no cases of avascular necrosis. Functional evaluation revealed generally good results. Patients scored a mean of 32.6 on the original Musculoskeletal Tumor Society scale and 95.8 on the revised version. The average Toronto Extremity Salvage Score was 91.3. With the numbers available, there were no significant differences between the study group and population norms in the Short Form-36. These results suggest that a uniform approach based on preservation of the femoral head can be applied successfully to the treatment of these lesions with good local tumor control, fracture healing, and acceptable functional outcomes.

Adolescent↗
PubMed2001

Applications of gene replacement technology to Streptomyces clavuligerus strain development for clavulanic acid production.

Cephamycin C production was blocked in wild-type cultures of the clavulanic acid-producing organism Streptomyces clavuligerus by targeted disruption of the gene (lat) encoding lysine epsilon-aminotransferase. Specific production of clavulanic acid increased in the lat mutants derived from the wild-type strain by 2- to 2.5-fold. Similar beneficial effects on clavulanic acid production were noted in previous studies when gene disruption was used to block the production of the non-clavulanic acid clavams produced by S. clavuligerus. Therefore, mutations in lat and in cvm1, a gene involved in clavam production, were introduced into a high-titer industrial strain of S. clavuligerus to create a double mutant with defects in production of both cephamycin C and clavams. Production of both cephamycin C and non-clavulanic acid clavams was eliminated in the double mutant, and clavulanic acid titers increased about 10% relative to those of the parental strain. This represents the first report of the successful use of genetic engineering to eliminate undesirable metabolic pathways in an industrial strain used for the production of an antibiotic important in human medicine.

Cephamycins↗
PubMed1999

In vitro and in vivo evaluation of effects of sodium caprate on enteral peptide absorption and on mucosal morphology.

Sodium salts of medium-chain fatty acids, sodium caprate (C10) in particular, have been used as absorption-enhancing agents to promote transmucosal drug absorption. In this study, we conducted both in vitro and in vivo experiments to investigate the effects of C10 on intestinal permeabilities and mucosal morphology. Mucosal addition of C10 (13-25 mM) reduced the transepithelial electric resistance (TEER) of cultured monolayers of the human intestinal cell line Caco-2 by 40-65% and, upon removal of C10, a marked tendency of TEER recovery was recorded. C10 added mucosally at 13-50 mM increased the transports of mannitol and polyethylene glycol (PEG) 900 across Caco-2 in a dose-dependent manner. In contrast, the transport of a model D-decapeptide was maximally enhanced with 20-25 mM C10. No noticeable morphological alteration of the Caco-2 monolayers was observed after a 1-h mucosal pretreatment with C10. Co-delivery with C10 (0.05-0.5 mmol/kg) into the rat terminal ileum increased the D-decapeptide bioavailability (BA) dose-dependently. With 0.5 mmol/kg C10 co-administered, D-decapeptide percent BA was elevated from 2 to 11%. Following a 1-h incubation with 0.5 mmol/kg C10 (in liquid or powder form) non-invasively delivered into the rectal lumen, no signs of histological change in the rectal mucosa were detected. These results demonstrate that C10 can promote intestinal absorption of a small peptide without causing detrimental alterations of the intestinal mucosa. C10 thus seems to be a good candidate as an enhancing agent for improving the oral BA of small therapeutic peptides.

Animals↗
PubMed1998

Repair of nasal defects using collagen gels containing insulin-like growth factor 1.

OBJECTIVE: Facial osseous defects are a common and challenging problem for the otolaryngologist-head and neck surgeon. Current methods of repair including synthetic grafts, cadaveric material, and autologous tissue have drawbacks of foreign body reactions, infectious agent transmission, and the morbidity of a second surgical site. In the effort to develop an ideal technique for osseous reconstruction, a critical-size facial defect has previously been developed in the Sprague-Dawley rat. This model exhibits less than 10% healing by surface area over 6 months. A novel approach to osseous reconstruction is attempted using this model with type I collagen gel augmented with insulin-like growth factor 1 (IGF-1). STUDY DESIGN: Randomized controlled trial using a rodent model. METHODS: Twelve adult male Sprague-Dawley rats underwent a surgical procedure to produce a critical-size nasal defect by removing the nasal bones with a cutting burr. Six animals were repaired with 300 microg of type I collagen gel. Six animals were repaired with 300 microg of type I collagen gel augmented with 3.0 microg of IGF-1. Thirty days later, the animals were examined after necropsy. Precise planimetry, radiodensitometric analysis, and histologic sectioning were performed. RESULTS: All animals had complete coverage of this defect with a thin layer of bone. Radiodensitometric analysis indicated that there was a statistically significant (P < .037) increase in bone density in the collagen plus IGF-1 group compared with that of collagen only. In addition, histologic evaluation revealed increased bone density and thickness in the IGF-1 group. CONCLUSION: Type I collagen gel augmented with IGF-1 results in a significant increase in healing of a nasal critical-size defect in a rodent model.

Absorptiometry, Photon↗