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Biomedical subjects

J E Hughes

Publications and source records attributed to J E Hughes.

At least 19 recordsLinked to original sources
PubMed1992

Selection of Dictyostelium discoideum transformants and analysis of vector maintenance using live bacteria resistant to G418.

A protocol that allows the rapid isolation and growth of large numbers of independent G418-resistant Dictyostelium discoideum transformant colonies on the surface of agar media with live bacteria was developed. Transformants grown under these conditions form normal fruiting bodies. Discovery that aggregation of nontransformants was inhibited at a nonselective level of G418 (25 to 35 micrograms/ml) led to the development of a vector maintenance assay. Using this assay we examined the stability of recombinant plasmids derived from the D. discoideum native plasmids Ddp1 and Ddp2. We conclude that the origin of replication of plasmid Ddp1 does not alone confer stable maintenance and thus, Ddp1 must bear additional sequences required for its own maintenance. Analysis of the maintenance of vectors derived from Ddp2 showed that autonomously replicating shuttle vectors that contained bacterial plasmid DNA and from which one element of the Ddp2 inverted repeat was removed were much less stable than vectors that contained a complete inverted repeat or that did not carry a bacterial plasmid. Sequences between the 3' end of the rep gene and the inverted repeat appear to play a role in plasmid maintenance. An intact rep gene and one copy of the inverted repeat element were required for extrachromosomal replication. Maintenance of extrachromosomal vectors was found to be strain dependent. Four traits distinguishing integrating vectors from those capable of autonomous replication were identified.

Animals↗
PubMed1991

Treatment of neoplastic spinal cord compression: results of a prospective study.

Currently, external radiation and steroid therapy are used in most patients with neoplastic spinal cord compression. Surgery is generally used to treat those who do not respond to radiation therapy. To determine the role of de novo surgery in patients with spinal metastases, a prospective study was undertaken. Over a 4 1/2-year period, the cases of 54 patients with radiologically documented spinal metastases were studied. The sites of tumor origin included soft tissue sarcoma (8 patients), kidney (6 patients), lung (5 patients), breast (5 patients), spine (6 patients), unknown primary site (6 patients), and others (18 patients). Sites of compression included the cervical spine segments in 15 patients, thoracic segments in 23, lumbar in 14, and sacral in 2. Before surgery, 24 patients (44%) were nonambulatory. Three surgical approaches were used: anterior vertebral body resection in 45 patients, laminectomy in 7, and lateral osteotomy in 2. After surgery, 37 patients received external radiation therapy. All patients improved (became ambulatory) after surgery, with 23 of 25 patients surviving at 2 years continuing to be ambulatory. The 30-day mortality rate was 6% (three patients); eight patients (15%) sustained various surgical complications. These results are superior to those reported after external radiation therapy and steroids alone, and they support the concept that de novo surgery be considered in selected patients with spinal metastases.

Adolescent↗
PubMed1990

The diagnosis and treatment of cerebral mycotic aneurysms.

Seventeen patients were treated for 28 documented cerebral mycotic aneurysms. Initial neurological symptoms were attributable to aneurysm rupture in only 7 patients, and in 3 of them symptoms did not suggest subarachnoid hemorrhage. Six patients presented with embolic infarction and 1 with meningitis; in 3 patients it was uncertain if aneurysm rupture occurred. Four patients had rupture of at least one aneurysm while receiving appropriate antibiotic treatment and another had rupture at the conclusion of therapy. Of 20 aneurysms followed angiographically or with computed tomography during medical treatment, 10 became smaller or disappeared and 10 remained unchanged or enlarged, 1 with fatal rupture. Eight ruptured aneurysms were surgically excised; 2 of the patients with ruptured aneurysms died and 2 had residual aphasia or cognitive impairment. All 4 patients whose only surgery was for an unruptured aneurysm made uneventful recoveries. Recognizing the retrospective and anecdotal nature of our data and the differing views of previous investigators, we recommend: (1) that careful neurological examination, computed tomography, and (unless contraindicated) lumbar puncture be performed on any patient with endocarditis; (2) that those with neurological abnormalities not attributable to systemic toxicity, including pleocytosis in the cerebrospinal fluid or apparent infarction on computed tomographic scans, undergo four-vessel cerebral angiography; (3) that single accessible mycotic aneurysms in medically stable patients be promptly excised, with individualization of multiple or proximal aneurysms; and (4) that repeat angiography be performed at the conclusion of antibiotic therapy in patients requiring long-term anticoagulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Treatment of spinal metastases from kidney cancer by presurgical embolization and resection.

Surgical treatment of bone metastases from kidney cancer is often complicated by profuse blood loss. The authors report the results of a retrospective review of 30 consecutive patients who underwent surgery for spinal metastases from kidney cancer. Seventeen patients (57%) were operated on after failing radiation therapy. Prior to operation, selective spinal angiography and embolization were performed in 17 patients with no permanent neurological deficits resulting. Gross total resection of the tumor and stabilization of the spine were then accomplished with acceptable blood loss. Twenty-seven (90%) of the 30 patients improved neurologically following surgery. There was a median survival time of 16 months, a 2-year survival rate of 33%, and a 5-year survival rate of 15%. Major surgical complications in this series were related to excessive blood loss in patients without embolization. These data suggest that patients with spinal metastases from kidney cancer should undergo spinal angiography and embolization prior to resection of the tumor. To improve upon current results, such treatment should be carried out prior to external radiation therapy.

Adult↗
PubMed1989

Neurosurgery in the treatment of cancer pain.

Patients with pain syndromes resulting from recurrent or metastatic cancer should be evaluated carefully to determine the cause of their pain and the need for appropriate antitumor treatment. Currently, opioid analgesics are the mainstay of pain control, but side effects limit their use in some patients. When pharmacologic pain control is inadequate or associated with intolerable side effects, neurosurgery should be considered. Currently the implantation of a pump for the intraspinal infusion of opioid analgesics is the most popular procedure, but its usefulness may be limited by the development of opioid tolerance. The most effective ablative pain control procedure at the current time is cordotomy, which is indicated in patients with unilateral pain. Although the place of neurostimulatory procedures in controlling cancer pain is not well established, they are attractive because of their nondestructive nature and potential usefulness in the treatment of bilateral pain syndromes. Specific antitumor surgical procedures should be considered in patients with certain spinal and plexopathy syndromes, because such intervention offers the prospect of both pain relief and tumor control. In this article, the neurosurgical procedures used in the management of cancer pain are reviewed.

Analgesics, Opioid↗
PubMed1989

Gene amplification associated with the dominant cob-354 cobalt resistance trait in Dictyostelium discoideum.

A DNA amplification is correlated with the dominant, unstable cob-354 cobalt resistance trait in the cellular slime mold, Dictyostelium discoideum. The amplified DNA is present as about 50 copies of an extrachromosomal element. Cells grown under nonselective conditions in the absence of cobalt ions lose both the cobalt resistance trait and all extrachromosomal copies of the amplified DNA. The amplified DNA is transferrable to new genetic backgrounds by parasexual genetic crosses. These results explain the inability to map the cob-354 trait to a linkage group. The chromosomal origin of the amplified DNA is group III or VI. Thus the resistance trait appears to be independent of the previously known cobalt resistance locus, cobA, which maps to group VII. A developmental defect involving the production of multiply-tipped aggregates that do not complete fruiting body formation also is correlated with the presence of the amplified DNA.

Animals↗
PubMed1989

Copy number control and compatibility of nuclear plasmids in Dictyostelium discoideum.

Copy number of the endogenous nuclear plasmids of Dictyostelium discoideum is a plasmid-specific trait. Copy number is stable over time, is constant relative to ploidy level, is independent of host cell genetic background, and is independent of the presence of a second unrelated plasmid in the same nucleus. Unrelated plasmids are compatible with one another within a single nucleus. Pairwise combinations of Ddp1, Ddp2, and Ddp5 were stably maintained over many generations in the absence of selection. In contrast, one of the D. discoideum plasmids (Ddp2) was incompatible with a recombinant plasmid derived from it (p7d2). In the absence of selection for retention of p7d2, transformants contain either one or the other but not both plasmids. The plasmids are stably maintained in host cells with differing genetic backgrounds, although plasmid-free colonies were detected at a frequency of about 1-2% in populations of some strains after 50 generations growth following a previous cloning.

Cell Nucleus↗
PubMed1989

A reticulo-frontal disconnection syndrome.

Persistent executive deficit, usually seen following prefrontal damage, is reported in a patient recovering from head trauma. Repeated neuroradidological examinations failed to reveal a lesion within the frontal lobes, but a circumscribed lesion in the ventral mesencephalic tegmentum was found. It is proposed that the observed syndrome was caused by damage to mesencephalic reticular nuclei and their projections into prefrontal cortex. The concept of a "reticulo-frontal disconnection syndrome" is introduced and its possible role in head trauma and schizophrenia discussed.

Adult↗
PubMed1989

Spondylectomy for malignant tumors of the spine.

Spondylectomy is the complete surgical removal of all parts of one or more vertebrae above the sacrum. We report our initial experience with spondylectomy in eight patients with malignant tumors of the spine operated on over a 7-year period (1980 to 1986). Four patients had primary neoplasms of the spine, and four others had solitary metastases to the vertebrae. Following surgery, five patients underwent radiation therapy (RT) and chemotherapy depending on histology of the tumor. Radiographic confirmation of tumor resection was obtained on all patients. Pain relief was noted in all patients, and six patients with preoperative neurological deficits improved. There was no surgical mortality, and one patient developed wound dehiscence following surgery. Six of the eight patients are alive with a median follow-up of 36 months, and local control was achieved in six of the eight patients. These preliminary data suggest that malignant tumors of the spine can be completely resected using a staged approach. In potentially responsive tumors, systemic chemotherapy is recommended between the two operations to reduce the risk of systemic dissemination.

Adult↗
PubMed1988

Nuclear plasmids in the Dictyostelium slime molds.

Cellular slime molds are one of only three types of eukaryotes known to contain circular nuclear plasmids. Unlike the 2-microns circle in Saccharomyces, different strains of Dictyostelium can carry different, nonhomologous plasmids. Covalently closed, circular DNA plasmids have been identified in D. discoideum, D. mucoroides, D. giganteum, and D. purpureum. These plasmids range in size from 1.3-27 kb and in copy number from 50-300 molecules per cell. Plasmids have been identified in approximately one-fifth of all isolates examined. The organization of their DNA in nucleosomes establishes their presence in the nucleus. We have successfully cotransformed endogenous Dictyostelium plasmids into D. discoideum using the G418 resistance shuttle vector B10S. Transformants carrying D. discoideum plasmids are recovered at much higher frequency than those carrying plasmids from the other Dictyostelium species. We have constructed recombinant plasmids based on the D. discoideum plasmid Ddp2 and the G418 resistance gene. With these extrachromosomal vectors, transformed cells are recovered at frequencies of up to 10(-4) per input cell, the vectors are stably maintained at high copy number in the absence of selection, and the vectors can be used to introduce foreign DNA sequences into D. discoideum cells.

Cell Nucleus↗
PubMed1988

The use of DNA probes for taxonomic study of dictyostelium wild isolates.

The classification of 27 wild isolates assigned to Dictyostelium discoideum on the basis of morphological criteria was reexamined using probes specific for DNA sequences cloned from the type strain NC4. These probes included ones specific for ribosomal spacer DNA regions and for a ribosomal RNA coding sequence, as well as probes for two chromosomal gene families (actin and discoidin) and for the DIRS-1 transposable element. Four isolates (AC4, WS526, WS584 and ZA3A) which had previously been shown to have unusual mating characteristics were distinctly different from other isolates. We interpret these differences as indicating that the four atypical isolates represent species other than D. discoideum. Probes for the ribosomal spacer DNA either did not hybridize to the DNA of these four isolates or had decreased levels of hybridization to EcoRI restriction fragments of different lengths to that observed with the type strain. With the discoidin probe, all isolates had DNA fragments that hybridized but AC4, WS526, WS584 and ZA3A lacked a pair of fragments that were conserved in NC4 and other isolates. With the actin probe, AC4, WS526, WS584 and ZA3A lacked numerous fragments that the other isolates shared with NC4. The DIRS-1 probes showed strong hybridization with ZA3A and weak hybridization to the other three isolates; however, the major EcoRI fragment in WS526 and WS584 was smaller than that in NC4 while ZA3A and AC4 had fragments of similar size to that in NC4.(ABSTRACT TRUNCATED AT 250 WORDS)

Cloning, Molecular↗
PubMed1988

Reoperation for brain metastases.

We report the results of reoperation for brain metastases in 21 patients with recurrent tumors following initial successful resection. The tumor recurrences were local (original site) in 14 patients, and occurred at other sites in the brain in the remaining seven. Time to CNS recurrence ranged from 3 to 30 months. At time of repeat craniotomy, disease was limited to the CNS in 12 (57%) of the patients. Median survival following second craniotomy was 9 months, and the actuarial 2-year survival was 25%. Neurological improvement was seen in two thirds of the patients; the median duration of neurological improvement was 6 months. There was no mortality, and only one patient developed increased deficit following surgery. We conclude that repeat resection of brain metastases is an important therapeutic option in selected patients, and should be considered in symptomatic patients with accessible mass lesions before the use of other experimental treatment.

Adult↗
PubMed1986

Depression and social stress among patients with benign breast disease.

One hundred and forty women referred to the Southampton breast clinic had a psychiatric interview at home, before their first clinic attendance. The 107 subsequently diagnosed as having benign breast disease had a high rate of depressive symptomatology in comparison with women in published surveys of the general population. In the year before referral, 25 (23 per cent) had had definite depression and 19 (18 per cent) had had borderline depression: at the time of interview 9 (8 per cent) had major depression and 22 (21 per cent) had minor depression. Depression in these patients was associated with recent life events and social difficulties. Mood disturbance and psychosocial stress may lead to medical consultation about benign breast disease, or even contribute to its development. Severe depression was less common in the 33 patients who turned out to have breast cancer, though more of them had minor depression, and they reported fewer recent life events.

Adult↗
PubMed1986

Intramedullary cysticercosis.

In 1976 a 28-year-old Ecuadoran male suffered paraparesis after a kick to his back. Iophendylate myelography was followed by thoracic laminectomy with incomplete resolution of the paraparesis. One year later, worsening of the paraparesis was managed by further thoracic laminectomy without improvement. In 1978 a spinal cord stimulator was implanted via low thoracic laminectomy as a measure to counter his spasticity. In 1984 metrizamide myelography and computed tomography scanning were performed for increasing spastic paraparesis that disclosed an intramedullary lesion at the T-4 level. Exploration and myelotomy revealed an intramedullary cysticercal cyst, which was totally removed.

Adolescent↗
PubMed1986

Postradiation sarcoma involving the spine.

Postradiation sarcomas arising many years after treatment of cancer are long term sequelae of therapy. We describe the clinical features, radiographic findings, and results of treatment in 13 patients with such sarcomas encountered over a 6-year period. Of these patients, 9 had bone sarcomas and the remaining 4 had paraspinal tumors arising from adjacent soft tissue and nerve. The primary cancer for which radiation was given included Hodgkin's disease (4 patients), breast cancer (2 patients), cervix cancer (2 patients), and a variety of others (5 patients). The latent interval to the occurrence of the second neoplasm varied from 6 to 30 years (median, 10 years) after treatment of the original tumor. Despite aggressive treatment, the overall prognosis was poor. The median survival was 8 months, with only 3 surviving more than 2 years. Although rare, postradiation sarcoma should be considered in the differential diagnosis of patients presenting with late onset of spinal pain or neurological symptoms after clinical remission of an original cancer.

Adolescent↗