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Biomedical subjects

S Russell

Publications and source records attributed to S Russell.

At least 19 recordsLinked to original sources
PubMed1995

Management of mitochondrial disease on an intensive care unit.

Patients with mitochondrial disease may present to the Intensive Care Unit (ICU) with a variety of neurological and general medical disorders. Eleven patients were admitted to a neurological ICU between 1970 and 1992 because of respiratory insufficiency, status epilepticus and/or metabolic encephalopathy associated with mitochondrial disease. Respiratory impairment occurred in eight patients and was associated with nocturnal hypoventilation due to respiratory muscle weakness, aspiration due to bulbar weakness and abnormalities of central control leading to a reduced CO2 drive, irregular respiratory patterns and sleep apnoea. Seven patients received continuous respiratory support during the acute illness; three were subsequently weaned to domiciliary ventilation, and four died. Five patients had stroke-like episodes, which in two were recurrent. Four patients developed tonic-clonic grand mal epilepsy associated with myoclonic fits (2 patients), absences (2), focal fits (1) and status epilepticus (2). Encephalopathy was associated with recurrent lactic acidosis (2 patients), cardiac failure (2), hyponatraemia (2), renal abnormalities (3) and complete heart block (1). Although rare, mitochondrial disease should be considered in any patient with unexplained respiratory failure, intractable epilepsy, lactic acidosis or recurrent stroke.

Acidosis, Lactic↗
PubMed1994

Persistence of dormant tumor cells in the bone marrow of tumor cell-vaccinated mice correlates with long-term immunological protection.

Live proliferation-competent and irradiated proliferation-incompetent L5178 murine lymphoma cells (Eb cell line) were compared for their potency to induce systemic anti-tumor immunity in syngeneic DBA/2 mice. The tumorigenic potential in vivo of live Eb cells was suppressed through local secretion of interleukin 4 (IL4) or alternatively by injection of parental cells at a site refractory to tumor growth. Inoculation of nontumorigenic doses of live Eb or Eb-IL4 cells led to long-lasting specific and systemic T-cell-mediated antitumor response requiring both CD4+ and CD8+ T lymphocytes. Irradiated cells offered only limited short-term protection, which could be marginally improved by IL4. The more effective protection offered by vaccination with live tumor cells correlated with rapid migration and persistence of tumor cells in the bone marrow of host animals after tumor cell inoculation. In contrast, irradiated Eb-lacZ cells had a short persistence. Tumor cells recovered from the bone marrow of host animals injected with live Eb-IL4 cells still expressed IL4. These observations indicate that in the course of vaccination with live Eb or Eb-IL4 cells, a fraction of these cells escaped destruction by host mechanisms and persisted in a dormant state in the bone marrow for long periods of time. Persistence of dormant tumor in the bone marrow correlated with the duration of anti-tumor immunity.

Animals↗
PubMed1994

Efficacy of 2'-deoxy-2'-fluororibosides against influenza A and B viruses in ferrets.

Single-dose treatments (5 to 40 mg/kg of body weight given intraperitoneally) of ferrets with 2'-deoxy-2'-fluoroguanosine or its prodrug, 2,6-diamino-purine-2'-fluororiboside, 1 h after infection with influenza A virus significantly inhibited replication of virus in the upper respiratory tract, resulting in amelioration of fever and nasal inflammation. Replication of virus in the lower respiratory tract was also reduced > 100-fold, but three doses were required to prevent replication in the lungs. In ferrets infected with influenza B virus, single-dose treatment (40 mg/kg given intraperitoneally) produced a similar but reduced response in comparison with that in ferrets infected with influenza A virus, indicating that dosing was not optimal for this virus.

Adenosine↗
PubMed1994

Discrimination between alternatively spliced STP-A and -B isoforms of CD46.

CD46 (membrane cofactor protein; MCP) is ubiquitously expressed on nucleated human cells; it has a protective function, binding C3b and C4b, which are then cleaved by serum factor I. CD46 molecules (55,000-65,000 MW) have four short consensus repeats (SCR): the function of SCR-1 and -2 is unknown; SCR-3 and -4 bind C3b and C4b. These are succeeded by the STP region, which can contain three separate regions (STP-A, -B, -C) rich in serine, threonine and proline and which are heavily glycosylated, succeeded by transmembrane and cytoplasmic tail regions (of which there are several). Multiple isoforms exist due to the different splicing of exons: STP-A and -B can thus be present or absent. So far these products can only be detected separately by polymerase chain reaction (PCR) and RNA studies; we now describe their detection by anti-peptide antibodies. Peptides whose sequences corresponded with those of STP-A and STP-B were synthesized and used for the immunization of mice; although they differ in only seven of 21 amino acids, monoclonal antibodies (mAb) that reacted specifically with STP-A but not with STP-B, and mAb that reacted specifically with STP-B but not with STP-A, were produced; these reacted specifically with native CD46 on human tissues and cell lines. STP-A mAb reacted with tissues in which STP-A RNA had been found, some leukaemias and cell lines; in normal tissue expression was mainly found in the intestine (large and small) and salivary gland. Anti-STP-B reacted with most tissues and cell lines. The antibodies should be of use in defining the expression and function of CD46 in different tissues.

Acetylgalactosamine↗
PubMed1992

Soemmering's ring support for posterior chamber intraocular lens implantation during penetrating keratoplasty. Changing trends in bullous keratopathy.

BACKGROUND: Changing trends in cataract extractions have resulted in a new category of bullous keratopathy: corneal decompensation after complicated extracapsular cataract extraction. These cases of bullous keratopathy are associated with rupture of the posterior capsule, vitreous loss, and significant intraocular inflammation at the time of the original complicated extracapsular cataract extraction. METHODS: The authors reviewed 14 consecutive cases of penetrating keratoplasty for bullous keratopathy in which posterior chamber intraocular lens implantation was supported by remnants of the posterior capsule and/or Soemmering's ring without suture fixation. All 14 patients had a history of complicated extracapsular cataract extraction with capsule rupture and vitreous loss. RESULTS: All 14 patients had clear, compact grafts without migration of the intraocular lens with a mean follow-up of 12.1 months. Vision improved in 93% of cases, and there was no significant worsening of glaucoma. CONCLUSIONS: Pseudophakic bullous keratopathy after traumatic extracapsular cataract extraction with an anterior chamber intraocular lens and aphakic bullous keratopathy after traumatic extracapsular cataract extraction are two relatively new clinical entities that present new intraocular lens management options. Bullous keratopathy after complicated extracapsular cataract extraction should be recognized as a distinct clinical entity. Intraocular lens implantation into the ciliary sulcus with Soemmering's ring and peripheral capsular support provide the advantages of a posterior chamber intraocular lens without the risk of iris or scleral sutures. The authors predict that bullous keratopathy associated with traumatic extracapsular cataract extraction will become one of the more common indications for penetrating keratoplasty.

Adolescent↗
PubMed1991

Bone marrow transplantation in children using closely matched related and unrelated donors.

Seventeen bone marrow transplants were undertaken on 15 patients with leukemia or aplastic anemia using marrow from closely matched (phenotypic or five out of six HLA-A, B and DR antigen matched related and unrelated) donors. Donors were siblings (four), parents (seven), aunt (one), great aunt (one) or matched unrelated (two). When compared with transplants using matched sibling donors, survival was not different (51.4 +/- 13.4% vs. 48.1 +/- 9.6%; p = 0.87) but transplant-related complications and morbidity were higher as follows: graft-versus-host disease (GVHD) (87% vs. 15%; p less than 0.001), interstitial pneumonitis (59% vs. 14%; p less than 0.003), days in hospital (51 vs. 26; p less than 0.001), and chronic transplant related morbidity 50% vs. 11%; p + 0.033). The age of donors who were closely matched was significantly greater than that of their recipients (29.7 +/- 13.9 years vs. 8.1 +/- 3.1 years; p less than 0.001) and was associated with poorer transplant outcome. Median transplant-related complication-free survival for patients receiving transplants from age non-disparate donors was 53 months (range 18-86 months) compared with 12 months (range 2-42 months) for age disparate donors (p = 0.028). Transplants from closely matched donors were undertaken in the ratio of one to every three matched donors, indicating the importance of this source of marrow in a transplant program.

Adult↗
PubMed1990

Site-directed recombination in the genome of transgenic tobacco.

The plant genome responds to the bacteriophage P1-derived loxP-Cre site-specific recombination system. Recombination took place at loxP sites stably integrated in the tobacco genome, indicating that the Cre recombinase protein, expressed by a chimeric gene also stably resident in the genome, was able to enter the nucleus and to locate a specific 34 bp DNA sequence. An excisional recombination event was monitored by the acquisition of kanamycin resistance, which resulted from the loss of a polyadenylation signal sequence that interrupted a chimeric neomycin phosphotransferase II gene. Molecular analysis confirmed that the excision had occurred. Recombination occurred when plants with the integrated loxP construction were stably re-transformed with a chimeric cre gene and when plants with the introduced loxP construction were cross-bred with those carrying the chimeric cre gene. As assayed phenotypically, site-specific recombination could be detected in 50%-100% of the plants containing both elements of the system. Kanamycin resistance was detected at 2-3 weeks after re-transformation and in the first leaf of hybrid seedlings. This demonstration of the effectiveness of the loxP-Cre system in plants provides the basis for development of this system for such purposes as directing site-specific integration and regulation of gene expression.

Blotting, Northern↗
PubMed1989

Gender differences in retrieval from long-term memory following acute intoxication with ethanol.

The present study investigated the effects of ethanol on retrieval from long-term memory by using a set of cognitive decision tasks. Male and female subjects were administered either 0.0 or 1.0 milliliter of ethanol per kilogram of body weight, and then asked to make physical, lexical, and semantic decisions about pairs of words. In general, intoxicated subjects responded significantly slower than sober subjects on all decision types. In addition, female subjects demonstrated greater performance deficits than males when intoxicated. The results suggested that the reduction in speed was not due to a simple slowing of motor responses. Rather the ethanol induced memory deficits may result from the slowing of cognitive operations that impair the efficiency of working memory. Several reasons were proposed for the observed difference in reaction to intoxication between male and female subjects, including neuroendocrine processes and cognitive differences.

Adult↗
PubMed1989

Recombinant interleukin-2 (rIL-2) given intrasplenically and intravenously for advanced malignant melanoma. A phase I and II study.

Recombinant interleukin-2 (rIL-2) was used to treat 31 patients with progressing metastatic malignant melanoma. Only three patients had disease confined to non-visceral sites; the median number of organ sites involved was four. The first dose of rIL-2 was given intrasplenically (to stimulate cytotoxic cells in high concentration) via a femoral artery catheter, and four further i.v. doses were given over 6 days. A total of three courses at 21-day intervals was planned. Doses were escalated in 15 patients from 1 x 10(6) to 16.4 x 10(4) Cetus units m-2. The maximum tolerated dose (11.0 x 10(6) U m-2) was used in the other 16 patients. Of the 71 courses, severe but transient toxicity requiring interruption of rIL-2 or additional care occurred on three courses (dyspnoea) and 15 from hypotension, but the patients' performance status improved. Four patients had partial tumour responses although in only one patient did response occur in all sites of disease. However, responses occurred in visceral sites and six patients are alive at 9-16 months. IL-2 is of use in advanced melanoma and does not need complicated ICU facilities.

Adult↗
PubMed1989

Characterization of the adenovirus proteinase: substrate specificity.

Peptides were synthesized based on the cleavage sites in the adenovirus type 2 proteins pVI and pVII. The synthetic peptides were incubated with disrupted, purified adenovirus as a source of proteinase and specific cleavages were monitored by fast protein liquid chromatography and amino acid analysis. Using this approach it was established that all the peptides cleaved were of the form M(L)XGX decreases G or M(L)XGG decreases X. Thus we have shown that the adenoviral proteinase recognizes a specific secondary structure formed by a sequence of at least five amino acids, the main determinants of specificity being two and four residues to the N-terminal side of the bond cleaved. We were able to examine the relevant structural features of the peptide substrates by utilizing the CHEM-X molecular modelling package. Using our consensus sequence we were able to predict the cleavage sites in the viral proteins pVIII, pre-terminal protein (pTP), 11K and IIIa. Octapeptides containing the predicted sites in pVIII and the pTP were synthesized and shown to be cleaved by the proteinase.

Adenoviruses, Human↗
PubMed1989

Nursing mosaic.

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Humans↗