Search PubMed⌕ Search

Biomedical subjects

J M Fox

Publications and source records attributed to J M Fox.

At least 19 recordsLinked to original sources
PubMed1998

Construction of pathogenic molecular clones of Aleutian mink disease parvovirus that replicate both in vivo and in vitro.

The ADV-G isolate of Aleutian mink disease parvovirus (ADV) replicates permissively in Crandell feline kidney (CRFK) cells but is nonpathogenic for mink, whereas the highly pathogenic ADV-Utah isolate is nonviable in CRFK cells. To assign control of host range in CRFK cells and pathogenicity to specific regions of the ADV genome, we constructed a full-length molecular clone chimeric between ADV-G and ADV-Utah. If either the map unit (MU) 54-65 (clone G/U-5) or MU 65-88 (clone G/U-7) sections were ADV-Utah, viability in CRFK cells was abolished, thus indicating that in vitro host range was controlled by two independent determinants: A in the MU 54-65 segment and B in the MU 65-88 segment. Determinant B could be divided into two subregions, B1 (MU 65-69) and B2 (MU 73-88), neither of which alone could inhibit replication in CRFK cells, an observation suggesting that expression of the B determinant required interaction between noncontiguous sequences. Adult mink of Aleutian genotype inoculated with G/U-8 or G/U-10 developed viremia, antiviral antibody, and histopathological changes characteristic of progressive Aleutian disease. The capsid sequences of G/U-8 and G/U-10 differed from ADV-G at five and four amino acid residues, respectively. Our results suggested that the host range and pathogenicity of ADV are regulated by sequences in the capsid protein gene.

Aleutian Mink Disease Virus↗
PubMed1998

Comparison of the native CCMV virion with in vitro assembled CCMV virions by cryoelectron microscopy and image reconstruction.

Cryoelectron microscopy and three-dimensional image reconstruction analysis has been used to determine the structure of native and in vitro assembled cowpea chlorotic mottle virus (CCMV) virions and capsids to 25-A resolution. Purified CCMV coat protein was used in conjunction with in vitro transcribed viral RNAs to assemble RNA 1 only, RNA 2 only, RNA 3/4 only, and empty (RNA lacking) virions. The image reconstructions demonstrate that the in vitro assembled CCMV virions are morphologically indistinguishable from native virions purified from infected plants. The viral RNA (vRNA) is packaged similarly within the different types of virions. The centers of all assembled particles are generally devoid of density and the vRNA packs against the interior surface of the virion shell. The vRNA appears to adopt an ordered conformation at each of the quasi-threefold axes.

Bromovirus↗
PubMed1998

A safety assessment of fixed combinations of acetaminophen and acetylsalicylic acid, coformulated with caffeine.

Overuse and abuse of phenacetin-containing mixed analgesics has contributed to end-stage renal disease. Combination analgesics, especially those coformulated with caffeine, have been implicated as imparting a greater risk of analgesic-associated nephropathy (AAN) than single or coformulated analgesics without caffeine. This has led to a recommendation that the sale of "two plus caffeine" analgesic mixtures be reclassified from over-the-counter to prescription only availability. There is a rational basis for coformulating acetylsalicylic acid (ASA) and acetaminophen (paracetamol) as this reduces the dose of each, without altering efficacy. The coformulation of caffeine with these analgesics has a significant adjuvant effect and increases analgesic efficacy 1.4-1.6-fold. Currently available animal and human data do not support the notion that the nephrotoxic risk from coformulated ASA and acetaminophen is higher than the risk from either ASA or acetaminophen alone, in equivalent analgesic doses. There are no epidemiological data that implicate caffeine in AAN, and only limited evidence that links excessive acetaminophen usage to renal disease. There is no evidence that caffeine increases analgesics papillotoxicity directly. The presence of caffeine in mixtures of analgesics are no more addictive than other sources of caffeine. There is no evidence to suggest that adding caffeine to analgesic mixtures enhances the potential for promoting analgesic misuse in the general population. Thus distinct therapeutic benefits of ASA, acetaminophen and caffeine appear to outweigh any known risk. It is doubtful if preventing the availability of these products will significantly affect the role of analgesic abuse/overuse in end-stage renal disease. Better risk management would come from a focused educational program, developed in a close collaboration between industry, healthcare professionals and consumer organizations, such a program must warn against the potential dangers of analgesic and non-steroidal anti-inflammatory drug misuse.

Acetaminophen↗
PubMed1998

Randomized trial of daily versus three-times-weekly prophylactic ganciclovir after lung and heart-lung transplantation.

BACKGROUND: Cytomegalovirus is an important cause of morbidity and mortality risk after lung transplantation. Ganciclovir, when given for a period of up to 3 months after lung transplantation, has been shown to reduce the incidence and severity of cytomegalovirus. However, daily prophylaxis is associated with considerable expense, inconvenience, and morbidity risk. The goal of this study was to determine whether 3-times-weekly dosage is as effective as daily prophylaxis with ganciclovir in preventing cytomegalovirus disease. METHODS: Seventy-two consecutive subjects who had either donor or recipient cytomegalovirus seropositivity were randomized to the daily group (n = 35) or the 3-times-weekly group (n = 37). All subjects received twice-daily ganciclovir treatment for 2 weeks. Thereafter, subjects received either daily or 3-times-weekly ganciclovir dosing until 90 days after transplantation. Subjects were then monitored for 28 +/- 13 months to identify outcomes and complications. RESULTS: There were no significant differences between the daily and 3-times-weekly groups with respect to survival free from cytomegalovirus infection or survival free from cytomegalovirus disease. In both groups, cytomegalovirus infection and disease frequently emerged after the termination of prophylaxis. However, in most cases the cytomegalovirus syndromes observed were mild and in many cases could be treated on an outpatient basis. There was no significant difference between the groups in the incidence of obliterative bronchiolitis or time to onset of grade 2 bronchiolitis obliterans syndrome. Overall patient survival was better in the daily group, but the survival advantage did not appear to be related to a reduction in cytomegalovirus-related disease. Complications of ganciclovir prophylaxis included leukopenia in 2 subjects in the 3-times-weekly group and catheter-related sepsis in 6 subjects from each group. CONCLUSIONS: We conclude that intravenous ganciclovir given 3 times weekly for 3 months after transplantation is as effective as daily ganciclovir given for a similar time period. The 3-times-weekly dosing regimen did not result in increased infection, disease, or sequelae of cytomegalovirus infection when compared with the daily regimen.

Antiviral Agents↗
PubMed1997

Characterization of a disassembly deficient mutant of cowpea chlorotic mottle virus.

An understanding of virus disassembly requires a detailed understanding of the protein-protein and protein-nucleic acid interactions which stabilize the virion. We have characterized a mutant of cowpea chlorotic mottle virus [cpR26C (coat protein R26C)] that displays increased virion stability and is abnormal in virion disassembly when purified under nonreducing conditions. Reduced virions are infectious, whereas nonreduced virions are noninfectious. The cpR26C mutant virions purified under nonreducing conditions resist disassembly in 0.5 M CaCl2, pH 7.5. The nonreduced cpR26C mutant virions swell in neutral pH conditions (pH 7.5) but do not disassociate when the ionic strength is increased. In contrast, wild-type virions or cpR26C mutant virions isolated under reducing conditions completely disassociate into the RNA and capsid protein components at pH 7.5 and high ionic strength (i > 1.0). Sequence analysis of the cpR26C mutant identified a single C to U nucleotide change at position 1435 of RNA 3 (position 86 of RNA 4), which results in a arginine to cysteine change at position 26 of the coat protein. The cpR26C mutant provides an ideal chemical switch for examining virion assembly and disassembly.

Bromovirus↗
PubMed1997

Virion swelling is not required for cotranslational disassembly of cowpea chlorotic mottle virus in vitro.

The mechanism by which virions of cowpea chlorotic mottle virus (CCMV) disassemble and allow for translation of the virion RNA is not well understood. Previous models have suggested that virion swelling is required to expose the virion RNA for translation in a process referred to as cotranslational disassembly (M. Brisco, R. Hull, and T. M. A. Wilson, Virology 148:210-217, 1986; J. W. Roenhorst, J. W. M. van Lent, and B. J. M. Verduin, Virology 164:91-98, 1988; J. W. Roenhorst, J. M. Verduin, and R. W. Goldbach, Virology 168:138-146, 1989). Previous work in our laboratory has identified point mutations in the CCMV coat protein which result in virions with altered swelling characteristics (J. Fox, F. G. Albert, J. Speir, and M. J. Young, Virology 227:229-233, 1997; J. M. Fox, X. Zhao, J. A. Speir, and M. J. Young, Virology 222:115-122, 1996). The wild-type and mutant CCMV virions were used to correlate virion swelling with the ability of virion RNA to be translated in a cell-free wheat germ extract. Mutant virions unable to swell (cpK42R) are as infectious as wild-type virions in vivo, and the levels of translated encapsidated virion RNA are similar to those of wild-type virions in vitro. Mutant virions capable of swelling but not of disassembling in vitro (cpR26C) are noninfectious and have severely reduced levels of translation of the encapsidated virion RNA in vitro. These studies suggest that virion swelling is not required for the cotranslational disassembly of CCMV. Additionally, the results indicate that there is a pH-dependent structural transition in the virion, other than swelling, that results in the RNA's being exposed for translation in vitro. An alternative model suggesting that cotranslational disassembly of CCMV involves presentation of the virion RNA through the virion fivefold axis is proposed.

Cell-Free System↗
PubMed1996

Analysis of a salt stable mutant of cowpea chlorotic mottle virus.

An understanding of virion assembly and disassembly requires a detailed understanding of the protein-protein and protein-nucleic acid interactions which stabilize the virion. We have characterized a mutant of cowpea chlorotic mottle virus (CCMV) that is altered in virion stability. The mutant virions resist disassembly in 1.0 M NaCl, pH 7.5, whereas the wild-type virions completely disassociate into RNA and capsid protein components. Sequence analysis of the mutant coat protein gene identified a single A to G nucleotide change at position 1484 of RNA 3 (position 134 of RNA 4), which results in a lysine to arginine change at position 42 of the coat protein. Introduction of the K42R mutation into wild-type CCMV coat protein results in a salt stable virion phenotype. Likewise, expression of the K42R mutant coat protein in Escherichia coli followed by in vitro assembly produces virions that exhibit the salt stable phenotype. Analysis of this mutation demonstrates how a single amino acid change in the primary structure of the coat protein leads to tertiary interactions which stabilize the virion.

Bromovirus↗
PubMed1996

Meniscal repair. Where do we go from here?

In summary, it has been the task of this article to try to forecast the future of meniscal surgery over the next decade. As we enter the twenty-first century, it becomes evident that a combination approach will be the most likely procedure. The code phrase will be, "Save as much meniscus as possible." The authors predict that accomplishing this objective will involve the use of adhesive materials, possibly autologous but more probably exogenous, supported by the insertion of a collagenous type material, which will serve as a scaffolding for the ingrowth of fibrocartilage, and the healing will be stimulated by hormonal methods. Whether this occurs through recombinant DNA techniques or better methods of precipitation remains an issue. Dose-specific mitogens and chemotactic agents will be placed in the area of injury to potentiate the vascular fibrous response of the host tissue. With earlier and more exuberant fibrous response and initial tissue adhesion from the fibrin adhesive, better stability will be established to allow for primary healing of meniscal tissues. This procedure will work well for longitudinal tears of the meniscus. A dilemma arises with more complex tears of the meniscus, however. Previously irreparable tears may be conducive to resection then replacement with cultured autologous fibrochondrocytes, either in a gel-type form or on scaffolds made of collagen or biodegradable materials. These scaffold/fibrochondrocyte replacements may be contoured to the defect present and bonded tightly with the fibrin adhesives previously discussed. Again, growth factors would be needed for ultimate success as the fibrochondrocytes mature into the appropriate morphologic subpopulations and begin to turn over their own extracellular matrix. The patient would have a neomeniscal autologous transplant with normal host cell turnover of matrix. A brave new era lies ahead for meniscal repair, and the journey promises to be a most exciting one.

Cartilage↗
PubMed1995

In vitro assembly of cowpea chlorotic mottle virus from coat protein expressed in Escherichia coli and in vitro-transcribed viral cDNA.

The small spherical plant virus, cowpea chlorotic mottle virus (CCMV), provides an ideal system to examine spherical virus assembly. We have modified the CCMV in vitro assembly system to produce virions from coat protein expressed in Escherichia coli and viral RNA transcribed in vitro from full-length cDNAs. Examination of the in vitro-assembled particles with cryoelectron microscopy and image reconstruction techniques demonstrates that the particles are indistinguishable from plant purified particles at 2.5 nm resolution. Mutational analysis of the coat protein N- and C-terminal extensions demonstrate their respective roles in virus assembly. The N-terminus is required for assembly of RNA containing particles but not for the assembly of empty virions. The C-terminus is essential for coat protein dimer formation and particle assembly.

Base Sequence↗
PubMed1994

Thermoregulation in Yersinia enterocolitica is coincident with changes in DNA supercoiling.

Yersinia enterocolitica is a facultative intracellular parasite, displaying the ability to grow saprophytically or invade and persist intracellularly in the mammalian reticuloendothelial system. The transition between such diverse environments requires the co-ordinated regulation of specific sets of genes on both the chromosome and virulence plasmid. Temperature has a profound pleiotropic effect on gene expression and phenotypically promotes alterations in cell morphology, outer-membrane protein synthesis, urease production, lipopolysaccharide synthesis, motility, and synthesis of genes involved in invasion of eukaryotic host cells. By examining thermoregulated flagella biosynthesis, we have determined that motility is repressed at 25 degrees C (permissive temperature) with subinhibitory concentrations of novobiocin. These conditions also induce virulence gene expression suggesting novobiocin addition simulates, at least partially, a high-temperature environment. Furthermore, temperature-shift experiments, using Y. enterocolitica containing pACYC184 as a reporter plasmid, indicate that thermo-induced alterations of DNA supercoiling coincide with temperature-induced phenotypic changes. A class of putative DNA gyrase mutant (novobiocin resistant) likewise demonstrates the 37 degrees C phenotype when cultured at 25 degrees C; it is non-motile, urease negative, calcium growth dependent, and positive for Yop expression. These results support a model implicating DNA topology as a contributing factor of Y. enterocolitica thermoregulation.

Bacterial Outer Membrane Proteins↗
PubMed1994

Malignant pleural effusion.

Pleural effusion is a frequent complication of malignant disease. With a realization of pathophysiological mechanisms, symptomatology, and specific care needs of patients, the nurse can make appropriate assessments and provide thorough and essential care to improve patient outcome.

Humans↗
PubMed1993

Trephination of incomplete meniscal tears.

The meniscus performs several roles that are important to the function of the knee joint. In an effort to preserve these functions of the meniscus, methods to promote the healing of meniscal lesions have been investigated. One such method involves trephination or the creation of vascular access channels by removal of a core of tissue from the periphery of the meniscus to the tear, thus connecting a lesion in the avascular portion of the meniscus to the peripheral blood supply. The purpose of this study is to describe our experience with arthroscopic trephination of symptomatic incomplete meniscal tears in humans. This is a simple technique that avoids the risk associated with suture repair of the meniscal tissue, yet preserves the meniscus. Overall results were good or excellent in 90% of the cases. In conclusion, symptomatic incomplete meniscal tears can be treated by stimulation of vascular channels without the risk associated with suturing of this tissue, while preserving the important functions of the meniscus.

Adult↗
PubMed1993

MR diagnosis of recurrent tears in the knee: value of intraarticular contrast material.

OBJECTIVE: After surgical resection or repair of a torn meniscus, the healed area may have areas of abnormal signal intensity on MR images. Consequently, routine MR imaging is not reliable for detecting recurrent meniscal tears. As a result, we studied the efficacy of MR imaging with intraarticular contrast material (MR arthrography) for detecting recurrent tears of the meniscus. SUBJECTS AND METHODS: Thirty-seven patients who previously had a meniscal tear treated by either meniscal resection or repair had conventional MR imaging and MR arthrography with 40-50 ml of a 1:100 solution of gadopentetate dimeglumine in saline. All patients had arthroscopy shortly after the MR studies. Follow-up arthroscopic surgery was performed within an average of 6.6 weeks after the MR arthrograms. The routine MR images and MR arthrograms were reviewed separately and randomly, and these results were compared with the arthroscopic findings. Meniscal morphology, signal intensity, and the presence of joint fluid tracking into recurrent tears were evaluated. RESULTS: The overall accuracy in diagnosing recurrent meniscal tears in the post-operative meniscus was 66% when conventional MR imaging was used and 88% when MR arthrography was used. In patients who had only minimal meniscal resection, both methods had an accuracy of 89%. In patients who had more extensive meniscal resection, accuracy was 65% with conventional MR imaging and 87% with MR arthrography. In four patients who had only a small meniscal remnant, the accuracy was 50% with routine MR imaging and 100% with MR arthrography. On conventional MR images, the presence of an effusion tracking into a meniscal tear had a sensitivity and positive predictive value of 90% for detection of recurrent meniscal tears; however, the sensitivity was only 41%. CONCLUSION: Our results show that the sensitivity of MR imaging in detecting meniscal tears after surgery varies with the extent of the resection. Sensitivity was considerably improved when intraarticular contrast material was used. MR arthrography should be considered as an alternative to arthroscopy in patients who have had resection or repair of the meniscus.

Adolescent↗
PubMed1993

Overuse injuries of the knee in basketball.

Overuse injuries of the knee are abundant in basketball players. This article discusses the pathophysiology of overuse and the principles of treatment. The diagnosis and clinical management of jumper's knee, patellofemoral pain, and stress fractures are outlined with specific attention to rehabilitation techniques and training.

Basketball↗
PubMed1992

Obliterative bronchiolitis after lung transplantation: a fibroproliferative disorder associated with platelet-derived growth factor.

Fibroproliferative disorders are characterized by accumulations of mesenchymal cells and connective tissue in critical locations, leading to organ dysfunction. We examined the role of platelet-derived growth factor (PDGF) in the pathogenesis of obliterative bronchiolitis, a fibroproliferative process that occurs after lung transplantation and results in small airway occlusion. Bronchoalveolar lavage fluid from obliterative bronchiolitis patients significantly stimulated fibroblast migration, whereas fluid from patient controls did not. Quantitation by radioligand binding assay demonstrated increased concentrations of PDGF in lavage fluid from obliterative bronchiolitis patients (patients, 104 +/- 26.9 pM; controls, 8.4 +/- 6.9 pM; P < 0.01). Heparin affinity, gel filtration, and Western blot analysis confirmed the presence of PDGF in lavage fluid. Immunohistochemical and in situ hybridization studies of histologic sections and bronchoalveolar lavage cells suggest that alveolar macrophages are one cellular source. Prospective evaluation of sequential bronchoalveolar lavage samples from a patient who developed obliterative bronchiolitis demonstrated markedly increased PDGF concentrations before the onset of irreversible airflow obstruction. These findings are consistent with a role for PDGF in the fibroproliferative changes observed in obliterative bronchiolitis.

Adult↗