Biomedical subjects

J O Bishop

Publications and source records attributed to J O Bishop.

At least 19 recordsLinked to original sources

PubMed1992

Management of acquired adult dropfoot.

Dropfoot is a catchall term for ankle equinus, equinovarus, and equinovalgus. The deformity can be flexible or rigid and may be associated with other pathology. In the adult, dropfoot may be congenital or acquired. Acquired dropfoot results from weakness of the ankle dorsiflexors, overpull of the plantarflexors, contracture of the soft tissues, bony deformity, or any combination of these factors. Appropriate treatment includes observation, orthotic devices, bracing, tendon transfers, arthrodesis, and neurolysis. The purpose of this paper is to review the pathophysiology and treatment of acquired dropfoot.

Adult↗

PubMed1992

Sexual dimorphism and growth hormone regulation of a hybrid gene in transgenic mice.

The sexually dimorphic expression of the urinary protein genes of mice (Mup genes) in the liver is mediated by the different male and female temporal patterns of circulating GH. Normal females were induced to male levels when GH was administered by injection to mimic the male GH pattern, showing that expression at the male level does not require a male sex steroid status in addition to intermittent GH. Two Mup-alpha 2u-globulin hybrid transgenes with different Mup gene promoters showed sexually dimorphic expression, and their expression in females increased to male levels upon testosterone treatment. GH-deficient (lit/lit) mice did not express these transgenes, and GH-deficient females did not respond to testosterone treatment, showing that GH was required for induction. Both normal and GH-deficient females were induced to male levels when GH was administered by injection. This is the first report of a transgene responsive to GH. A transgene consisting of a Mup promoter fused to a Herpes simplex virus thymidine kinase reporter sequence also showed sexual dimorphism, although to a lesser degree. It was expressed at the same level in normal females and GH-deficient mice of both sexes and was induced when GH-deficient mice were treated with GH. We propose that this transgene has a basal constitutive expression, possibly due to the absence of any rodent DNA downstream of the promoter. Since expression of the transgene was significantly induced by GH, the GH response is due at least in part to sequences in the promoter region.

Alpha-Globulins↗

PubMed1991

Solitary myeloma of the talus bone.

Solitary myeloma can present as either extramedullary plasmacytoma or solitary plasmacytoma of bone (SPB). More than half of reported cases of SPB are localized to the spine. The rest include appendage long bones of the skeleton, pelvis, and skull. The first case of SPB (to the authors' knowledge) is reported involving the talus bone of the foot. Although approximately 50% of SPB patients progress to multiple myeloma in the first 3 years after diagnosis, aggressive local therapy is indicated because the median survival of patients with SPB is better than that for multiple myeloma.

Bone Neoplasms↗

PubMed1991

The herpes simplex virus type 1 thymidine kinase is expressed in the testes of transgenic mice under the control of a cryptic promoter.

We reported previously that the herpes simplex virus type 1 (HSV-1) thymidine kinase reporter gene (tk) was expressed in the testes of transgenic mice when coupled to the promoter of a liver-specific mouse major urinary protein (MUP) gene. Here we show that HSV-1 tk is also expressed in the testis when coupled to a MUP pseudogene promoter, to a truncated MUP promoter that is not active in the liver, and to the promoter of the bovine thyroglobulin gene. Furthermore, HSV-1 tk itself was expressed in the testis, although its normal expression had been disabled by removing an upstream regulator of transcription. In every case, the same multiple transcripts were observed, with their 5' ends located downstream of the normal HSV-1 tk translation initiation codon. We conclude that the transcription of HSV-1 tk in the testis is directed by a cryptic TATA box-independent promoter located in the coding region of the gene. The longest HSV-1 thymidine kinase (TK) polypeptides synthesized in the testis were shorter than full-length TK and probably result from translational initiation at Met46 and Met60, the second and third ATG codons of the tk reading frame. Male mice of most transgenic lines were sterile, and the severity of the lesion in spermatogenesis was directly related to the level of TK expression. In the most highly expressing lines, sperm counts were low and morphologically defective sperm were common. In other sterile lines, TK was expressed at a lower level and sperm counts were normal but sperm motility was greatly reduced. Lines with the lowest levels of HSV-1 TK expression were fertile. HSV-1 TK was expressed in germ line cells, mainly in the haploid spermatids. However, low-level HSV-1 TK activity was found in the testis before the first germ cells entered meiosis, showing that if expression is confined to the germ cells, it also occurs in spermatogonia.

Animals↗

PubMed1991

Specific ablation of thyroid follicle cells in adult transgenic mice.

The coding region of the herpes simplex type 1 virus thymidine kinase gene was coupled to the promoter of the bovine thyroglobulin gene and introduced into the genome of mice. The viral thymidine kinase (HSV1-TK) was expressed mainly in the thyroid glands and testis. Upon treatment of transgenic females with the antiherpetic agent Ganciclovir the thyroid regressed, while the parathyroid gland was unaffected. The number of thyroid follicle cells was greatly reduced after 3 days, and they were completely absent after 7 days of treatment. After 14 days, the levels of circulating T4 and T3 were below the limits of detection, total soluble protein recovered from the thyroid and parathyroid glands together was 10% of the control value, and the level of thyroid HSV1-TK was more than 100-fold lower than that in transgenic controls. Levels of circulating PTH and calcitonin remained normal. At the time of treatment the mice were adults. Thus, the thyroid follicle cells were selectively ablated after normal development with a functional thyroid gland. When treatment with Ganciclovir was terminated after 14 days, no circulating T4 or T3 or other indications of thyroid regeneration were detected for a subsequent period of 90 days. During this time the mice gained weight more slowly than controls, at a rate consistent with the suppression of GH synthesis by thyroid deficiency. The production of mouse major urinary protein (MUP) ceased in the treated mice and was completely restored by the administration of T4. MUP production was not restored by GH, demonstrating that the expression of the Mup genes requires T4 in addition to GH.

Animals↗

PubMed1991

Use of a hinged silicone prosthesis for replacement arthroplasty of the first metatarsophalangeal joint.

A series of ninety consecutive total joint replacements of the first metatarsophalangeal joint with a flexible hinged prosthesis was reviewed after an average duration of follow-up of three years (range, twenty-four to sixty-one months). Although subjectively the results were satisfactory in most of the patients, and pain, the most common preoperative symptom, was reduced, mechanical failure of the implant was common, as determined radiographically. The frequency of failure of the implant and the extent to which it failed were related to the length of time that the implant had been in place. The range of motion of the metatarsophalangeal joint was decreased from normal. Dorsiflexion averaged 26 degrees and plantar flexion, 18 degrees. Callosities under at least one metatarsophalangeal joint were noted in fifty (69 per cent) of the feet that had a physical examination. Pedobarographic analysis of the distribution of plantar pressure revealed that none of the patients exerted weight-bearing pressures on the affected great toe. However, the subjective results were not significantly associated with radiographic evidence of failure of the implant. Despite its success in relieving the symptoms in our patients, we have abandoned this procedure because of the high and increasing rate of failure of the implant, as demonstrated radiographically.

Adult↗

PubMed1990

Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1.

Nucleotide sequences in three hypervariable regions of the human immunodeficiency virus type 1 (HIV-1) env gene were obtained by sequencing provirus present in peripheral blood mononuclear cells of HIV-infected individuals. Single molecules of target sequences were isolated by limiting dilution and amplified in two stages by the polymerase chain reaction, using nested primers. The product was directly sequenced to avoid errors introduced by Taq polymerase during the amplification process. There was extensive variation between sequences from the same individual as well as between sequences from different individuals. Interpatient variability was markedly less in individuals infected from a common source. A high proportion of amino acid substitutions in the hypervariable regions altered the number and positions of potential N-linked glycosylation sites. Sequences in two hypervariable regions frequently contained short (3- to 15-bp) duplications or deletions, and by amplifying peripheral blood mononuclear cell DNA containing 10(2) or 10(3) proviral molecules and analyzing the product by high-resolution electrophoresis, the total number and abundance of distinct length variants within an individual could be estimated, providing a more comprehensive analysis of the variants present than would be obtained by sequencing alone. Sequences from many individuals showed frequent amino acid substitutions at certain key positions for neutralizing-antibody and cytotoxic T-cell recognition in the immunodominant loop. The rates of synonymous and nonsynonymous nucleotide substitution in the region of this and flanking regions indicate that strong positive selection for amino acid change is operating in the generation of antigenic diversity.

Amino Acid Sequence↗

PubMed1990

Concurrent evolution of human immunodeficiency virus type 1 in patients infected from the same source: rate of sequence change and low frequency of inactivating mutations.

Direct sequencing of segments of the envelope gene of human immunodeficiency virus type 1 proviruses in peripheral blood mononuclear cells has revealed that a cohort of hemophiliacs who were infected after exposure to a single common batch of factor VIII share closely related virus strains. Seventy-four sequences extending from hypervariable regions V4 through V5 from nine patients yielded a mean intrapatient nucleotide distance of 5.5%, while a mean of 4.2% was observed in 39 sequences of the V3 loop (six patients). Phylogenetic analysis revealed that sequences of six Edinburgh patients were particularly closely related and those from a patient infected in the United States were very distinct. The mean nucleotide distance among these six was 8.3%, while the mean distance from the U.S.-derived sequences was 25.5% in the V4-V5 region. The rate of sequence change across this patient group has been estimated to be 0.4% per year in the V4-V5 region and 0.5% per year in the V3 region, with at least a twofold range across patients. Only two inactivating nucleotide substitutions have been observed in a total of 42 kb of sequence obtained from the env and gag genes during this study.

Base Sequence↗

PubMed1990

Human immunodeficiency virus-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers.

In human immunodeficiency virus (HIV)-infected individuals, the proportion of circulating mononuclear cells (PBMCs) which carry HIV provirus and the number of HIV proviral sequences per infected PBMC have been matters for conjecture. Using a double polymerase chain reaction which allows the detection of single molecules of provirus and a method of quantifying the provirus molecules, we have measured provirus frequencies in infected individuals down to a level of one molecule per 10(6) PBMCs. As a general rule, only a small proportion of PBMCs contain provirus (median value of samples from 12 patients, one per 8,000 cells), and most if not all of the infected cells carry a single provirus molecule. The frequency of provirus-carrying cells correlated positively both with the progression of the disease and with the success with which virus could be isolated from the same patients by cocultivation methods. Of seven asymptomatic (Centers for Disease Control stage II) patients, all but one contained one provirus molecule per 6,000 to 80,000 cells; of five Centers for Disease Control stage IV patients, all but one contained one provirus molecule per 700 to 3,300 cells. When considered in conjunction with estimates of the frequency of PBMCs that express viral RNA, our results suggest that either (i) the majority of provirus-containing cells are monocytes or (ii) most provirus-containing lymphocytes are transcriptionally inactive. We also present nucleotide sequence data derived directly from provirus present in vivo which we show is not marred by the in vitro selection of potential virus variants or by errors introduced by Taq polymerase. We argue from these data that, of the provirus present in infected individuals, the proportion which is defective is not high in the regions sequenced.

Base Sequence↗

PubMed1990

Expression of a foreign gene in a line of transgenic mice is modulated by a chromosomal position effect.

Unusual aberrant expression of a foreign gene in a particular transgenic mouse line is often attributed to chromosomal position effect, although proof of this is lacking. An alternative explanation is that expression has been modified by the arrangement of multiple copies of the foreign gene at the insertion site or by mutation or gene rearrangement. We have distinguished between these explanations in the case of one particular transgenic line by recovering the aberrantly expressed foreign DNA and reintroducing it into the mouse genome to produce secondary transgenic mice. The expression pattern of the gene in the secondary transgenic mice was normal, showing that this case of aberrant expression is due to a chromosomal position effect.

Animals↗

PubMed1990

An anatomic study of subtalar instability.

Subtalar instability has been recognized as a cause of ankle symptoms. The purpose of this anatomic study is to determine the ligament damage required to produce subtalar instability, and to define a radiographic technique to demonstrate it. Ten fresh adult cadaver ankles were dissected. Selective sectioning of the calcaneofibular ligament, capsule, and interosseous ligaments of the subtalar joint were done. Radiographic documentation of subtalar opening was recorded, using a lateral and Brodan's view. Sectioning of the calcaneofibular ligament alone produced a 5-mm opening of the subtalar joint. When combined with sectioning of the interosseous ligament, a 7-mm opening was produced. This was reproduced with a plantar flexion-supination load to the foot. Instability of the ankle joint (talar tilting) was produced only when loading caused additional tearing of the anterior talofibular ligament. This study suggests that surgical repairs to correct lateral ankle instability should include repair or substitution of the calcaneofibular ligament if subtalar instability is a consideration.

Humans↗

PubMed1990

Acute lateral ankle ligament injuries: a literature review.

The average general orthopaedic surgeon examines and treats a considerable number of acute lateral ankle ligament sprains in a busy office practice. A cursory review of recent articles published on this subject will present a confusing picture regarding diagnosis and treatment of Grade III injuries. An air of controversy surrounds the interpretation of diagnostic x-rays, and the management of these common ankle problems. This review article is presented to summarize current thoughts on the anatomy, biomechanics, diagnosis, and treatment of acute lateral ankle ligament sprains.

Adolescent↗

PubMed1989

Intraspecific evolution of a gene family coding for urinary proteins.

The genome of the laboratory mouse contains about 35 major urinary protein (MUP) genes, many of which are clustered on chromosome 4. We have used distance and parsimony methods to estimate phylogenetic relationships between MUP genes from nucleotide sequence and restriction maps. By analyzing coding sequences we show that the genes fall into four main groups of related sequences (groups 1-4). Comparisons of restriction maps and the nucleotide sequences of hypervariable regions that lie 50 nucleotides 5' to the cap sites show that the group 1 genes and probably also the group 2 pseudogenes fall into subgroups. The most parsimonious trees are consistent with the evolution of the array of group 1 and 2 genes by mutation accompanied by a process tending toward homogenization such as unequal crossing-over or gene conversion. The phylogenetic grouping correlates with grouping according to aspects of function. The genomes of the inbred strains BALB/c and C57BL contain different MUP gene arrays that we take to be samples from the wild population of arrays.

Animals↗

PubMed1989

Differential expression in male and female mouse liver of very similar mRNAs specified by two group 1 major urinary protein genes.

The major urinary proteins of the mouse are encoded by a large multigene family composed of several distinct groups of genes distinguished by differences in sequence and expression characteristics. The genes in the largest group (group 1) show greater than 99% pairwise similarity in their exons. By hybridization between RNA and a specifically designed oligonucleotide, we confirmed that genes of this group are expressed mainly in the liver. By using additional gene-specific oligonucleotide probes, we have been able to distinguish between the species of mRNA corresponding to two of these genes and to measure their abundance in male and female liver. Both mRNAs are present in male liver at high but different levels. Both are also present in female liver, one at a much lower level than in the male and the second at a very low level indeed. Both are present at male levels in the livers of females induced with testosterone. These results show unequivocally that the expression of different group 1 Mup genes is differentially influenced by the hormonal status of the mouse.

Animals↗

PubMed1989

Metatarsal osteotomy for primary metatarsalgia: radiographic and pedobarographic study.

The effect of surgical procedures for primary metatarsalgia on the load distribution and bony architecture of the forefoot is poorly understood. A prospective study was performed on 45 feet with this diagnosis treated by dorsal wedge osteotomy and compared with 29 symptom-free contralateral feet. Each foot was evaluated preoperatively and postoperatively with quantitative radiographic analysis, a pedobarographic study, and by physical examination. Following osteotomy there was a 4.5-mm increase in average height from ground and a 7.0 psi decrease in pressure. The symptom-free control group demonstrated no statistically significant changes. Residual pain occurred with an average height increase of less than 3.5 mm and an average pressure decrease of less than 1.5 psi. Transfer lesions developed in three of four patients with a height increase of greater than 4.5 mm. The symptoms of metatarsalgia are altered by changes in height of the metatarsal or the pressure beneath it. It is not possible to predict the surgical elevation of the metatarsal head required to precisely decrease the pressure beneath the metatarsal head, thereby eliminating symptoms.

Adult↗

PubMed1989

Mechanism of chromosomal integration of microinjected DNA.

Most transgenic animals have been produced by directly injecting DNA into one of the embryo pronuclei in the period immediately following fertilization. Transgenic animals are produced when DNA becomes integrated into the chromosomes, in most cases the transgenic genotype is transmitted to progeny through the germ line. The characteristics of the foreign DNA include tandem arrangement of multiple copies of the input DNA, predominantly in direct rather than inverted orientation, and illegitimate recombination with the chromosome at the site of integration. Foreign DNA integrated into chromosomes of cultured cells has identical characteristics. We argue that these and other similarities between the integration of foreign DNA into the chromosomes of microinjected embryos on the one hand and on the other of transfected and microinjected cells, strongly suggest that the processes have the same basis. By considering mainly the literature relating to cell transfection and microinjection, we conclude that tandemly arranged concatemers of input foreign DNA are built up by a process of homologous but non-conservative recombination. End-joining and illegitimate recombination events characterize the integration of the concatemers into the chromosome, and also contribute to the formation of the concatemers. We also suggest that these superficially different processes are based on the same opportunistic repair-ligation mechanism; the frequencies of the different types of event reflect both the frequencies with which different sorts of association occur between DNA molecules and their relative stability.

Animals↗

PubMed1988

A Mup promoter-thymidine kinase reporter gene shows relaxed tissue-specific expression and confers male sterility upon transgenic mice.

A hybrid gene was made by fusing the 2.2-kilobase 5' promoter region of a mouse group 1 major urinary protein (Mup) gene to the coding region of the herpes simplex virus type 1 thymidine kinase gene (HSV tk) and introduced into the genomes of mice by microinjection. Transgenic G0 males were sterile, or when fertile did not transmit the foreign gene, and the transgenic male descendants of G0 females were also sterile. Seven "lines" were established by breeding from G0 females and their transgenic female descendants. Six lines expressed HSV thymidine kinase activity in the liver, and activity correlated perfectly with the presence of HSV tk RNA. In three of four lines examined, expression was lower in female than in male liver, and in these lines the same sex difference was observed in the rate of run-on transcription of the foreign genes in liver nuclei. When females of one of the sexually dimorphic lines were treated with testosterone, the levels of HSV tk RNA and thymidine kinase activity were increased, although not to male levels. In these aspects of liver expression, and also in a lack of expression in seven other tissues, the hybrid gene exhibits many of the characteristics of an endogenous group 1 Mup gene. However, the gene was also expressed (at high levels) in the preputial gland and testis, two tissues in which Mup genes are not expressed. The gene, when introduced into five of the seven lines, carried a copy of the Escherichia coli supF gene attached beyond the 3' end of the HSV tk gene, but this did not affect the overall expression pattern. All of the lines were male sterile and expressed HSV thymidine kinase in the testis, but one line showed no activity in the liver, and another showed none in the preputial gland. Testicular expression is therefore the likely cause of sterility. Data are described which suggest that the causes of misexpression in the preputial gland and testis are different. Since expression in each tissue occurred in several lines, the structure of the hybrid gene must be responsible in each case. Five intensively studied lines showed at least four consistently different patterns of relative expression in preputial gland, testis, male liver, and female liver. These differences do not correlate in any way with the copy number of the foreign gene in the different lines and must be due to some other aspect of line specific integration.

Animals↗

PubMed1988

Tissue-specific gene expression in mouse hepatocytes cultured in growth-restricting medium.

Culture conditions which maintain hepatocytes in their in vivo state are not known. This hampers the study of liver gene expression and of direct responses of liver genes to hormonal stimulation. We argued that hepatocytes that were unable to divide might retain in vivo characteristics. We therefore plated mouse (BALB/c) hepatocytes on plastic dishes in medium lacking arginine and measured the levels and transcription rates of six tissue-specific mRNAs over a period of days. Alpha-fetoprotein mRNA began to accumulate at about 48 h of culture, and transcription could sometimes be detected after 72 h. The levels and transcription rates of four mRNAs (albumin, alpha-1-antitrypsin, apolipoprotein A1, and major urinary protein [MUP]) fell sharply. The rate of transcription of transferrin mRNA fell less rapidly, and its level remained high, partly due to its longer half-life. The overall pattern of gene expression in the plated cells did not exactly parallel that of either fetal or regenerating liver. The hepatocytes remained responsive to hormonal stimulation. Insulin and dexamethasone each tended to counteract changes in mRNA levels, for example, preventing the accumulation of alpha-fetoprotein mRNA. The effects of insulin were primarily due to changes in transcription rates. Bovine growth hormone and thyroxine elevated the levels of most of the mRNAs. Many of the effects of these hormones, when added singly, could not be ascribed to changes in transcription. The level of MUP mRNA was strongly affected by added hormones. The mRNA level at 5 days was increased by added insulin, dexamethasone, growth hormone, and thyroxine. In the presence of these three hormones, the decay in the transcription rate of the MUP genes was reduced about 10-fold. We conclude that hepatocytes plated under these nongrowing conditions can provide insights into the hormonal responsiveness of tissue-specific genes.

Animals↗