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Biomedical subjects

G Martin

Publications and source records attributed to G Martin.

At least 523 records · Page 29Linked to original sources
PubMedDate not supplied

Preclinical safety testing of DISC-hGMCSF to support phase I clinical trials in cancer patients.

BACKGROUND: DISC-hGMCSF is a gH-deleted HSV-2 based vector expressing human GM-CSF that is being developed for cancer immunotherapy. To support first clinical use, a range of preclinical safety studies were performed using DISC-hGMCSF in addition to DISC-murine-GMCSF and the backbone vector, TA-HSV. METHODS: The toxicity of the DISC vectors was assessed by repeated dose, neurovirulence and neuroinvasiveness studies in mice, and by safety studies in rabbits, guinea pigs and athymic nude mice. Studies were also conducted to determine whether the vector could establish latency in local ganglia in mice following intradermal injection, and whether it could reactivate from the latent state. The vector biodistribution following intravenous administration was also investigated in mice, using PCR to detect vector DNA. RESULTS: The DISC vectors were essentially non-toxic in all the systems studied. No adverse reactions were seen in mice receiving four intravenous doses of DISC-mGMCSF and the results from studies of neurovirulence, neuroinvasiveness, local tolerance in rabbit, general safety in mice and guinea pigs and safety in athymic nude mice were consistent with DISC being unable to replicate and cause disease. The vector could establish latency in local ganglia in mice, but at low efficiency, and could not reactivate infectious virions. Following intravenous administration, vector DNA was widely distributed up to Day 28, but by Day 56 had disappeared from gonads and brain and was only found in blood and liver. CONCLUSION: The panel of safety studies provided evidence that DISC-hGMCSF will be unable to replicate and cause disease, and has low toxicity in man. These data were presented to the Medicines Control Agency and the Gene Therapy Advisory Committee as part of the regulatory submissions for a clinical trial in melanoma patients. These submissions have been approved, and DISC-hGMCSF has now entered a phase I clinical trial in the UK by direct intratumoural injection.

Animals↗
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DNA bending induced by specific interaction of decamer binding proteins with immunoglobulin gene control sequences.

In order to investigate the properties of specific DNA-binding proteins involved in tissue-specific regulation of immunoglobulin genes, we have analyzed the interaction of nuclear proteins from mouse B-cell hybridomas with promoter and enhancer sequences of a mouse immunoglobulin heavy chain gene. Visualization of specific complexes has shown that protein binding induces a sharp bend at the position of the conserved decamer sequence. After fractionation of nuclear extracts, several sequence-specific DNA binding proteins could be distinguished by UV crosslinking to radioactive synthetic oligonucleotides. Decamer binding factor I (DBF-I) a protein of 100-105 kDa and DBF-II, a family of proteins of 25-35 kDa were purified on specific DNA-affinity columns. Both proteins bend the DNA at the dc sequence as shown by electron microscopy and by gel retardation. These data suggest that one possible function of sequence-specific regulatory proteins may be to locally change the DNA topology, thereby facilitating the interaction of additional transcription factors with the primary complex.

Animals↗
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5-HT receptor classification and nomenclature: towards a harmonization with the human genome.

Molecular biology has dramatically advanced our knowledge and understanding of receptors for 5-hydroxytryptamine (5-HT). The existence of multiple 5-HT receptors defined using traditional pharmacological and biochemical approaches has now been amply confirmed, but gene products encoding putative "new" 5-HT receptors have also been discovered. In some cases, the absence of suitably selective agonists and antagonists has hampered determination of a physiological role for these gene products. This makes their classification as formally recognised receptors premature.

Animals↗
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[Value of electroencephalographic serveillance in the framework of resuscitation in coma caused by acute drug intoxication].

The authors carried out long-term clinical and E.E.G. studies on 100 cases of acute drug poisoning. They made the following conclusions: - in unexplained coma, the E.E.G. can indicate toxic aetiology and may sometimes even suggest which drug is responsible, especially for certain chemical groups (barbiturates, phenothiasines, benzodiazepines); - the E.E.G. picture contributes a valuable indication of the depth of coma; the way in which it evolves affects the prognosis; - the effectiveness of therapy may be judged by monitoring cerebral electrical activity.

Acute Disease↗
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Efficacy of 24-hour shifts: prepared or impaired? A prospective study.

BACKGROUND: The effect of duty duration on performances is unknown. In a prospective cohort study model using repeated measures, we evaluated the effect of shift length on a battery of neuropsychologic performance indicators using our flight program as the test site. METHODS: Flight nurses completing 24- and 12-hour shifts were tested on memory, attention, reasoning, motor, and speed measures. Ratings of stress, fatigue, sleep quality, and logged amount of work and sleep were evaluated from personal journals kept for this purpose. Data were analyzed by linear regression and repeated measures multivariate analysis of variance (MANOVA) and analysis of variance (ANOVA). Clinical significance was set at P < 0.05. RESULTS: Fifteen subjects completed the testing and evaluation process. Neuropsychologic testing demonstrated that performance was not predicted by shift length, time of shift (day versus night), amount or quality of sleep before or during shift, or fatigue ratings. Age, gender, and education did not mediate shift length/test performance relationships. Uninterrupted sleep, stress ratings, and number of flights per shift modestly reduced some test scores. Predictably, repeated testings resulted in practice effects that reduced analysis power. We found that 24-hour shifts per se do not result in a cognitive decline compared with 12-hour shifts. Inconsistent sleep, number of flights, and the stressfulness of flights may have greater impact.

Air Ambulances↗
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Isolation of a cDNA clone coding for a possible neural nicotinic acetylcholine receptor alpha-subunit.

We have isolated a complementary DNA clone containing sequences homologous to those encoding the alpha-subunit of a mouse muscle nicotinic acetylcholine receptor. Based on the structural similarities between the encoded protein and the muscle acetylcholine receptor alpha-subunit, and the presence of hybridizing RNA species in the brain, we propose that this clone codes for a neural nicotinic acetylcholine receptor alpha-subunit.

Amino Acid Sequence↗
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Monoclonal antibodies to promote marrow engraftment and tissue graft tolerance.

Allogeneic reactions are the major limitation to organ transplantation. These are manifested as rejection of the grafted tissue, and also, in the case of bone marrow transplantation (BMT), graft-versus-host disease (GVHD). Recent methods of avoiding GVHD, by depleting T cells from donor marrow, have led to an increased incidence of marrow graft rejection. Current recipient conditioning protocols involving drugs or irradiation cannot safely be increased, so alternatives must be found. Monoclonal antibodies can be used to control immune responses in vivo, and would be useful in this context if we could define and deplete the cells responsible for marrow rejection. We show here that elimination of residual L3T4+ and Lyt-2+ cells from mice receiving fully mismatched bone marrow abrogates rejection and promotes tolerance to donor-type skin grafts, even in sub-lethally irradiated recipients.

Animals↗
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Suspected extragonadal germ-cell cancer syndrome presenting with an orbital mass and elevation of serum CEA, CA 19-9 and CA50 levels.

Patients with extragonadal germ-cell cancer syndrome (EGCCS) represent a subgroup of patients with poorly differentiated carcinoma or adenocarcinoma of an unknown primary site for whom potentially curative therapy is available. We report the case of a young man presenting an orbital tumor and high serum levels of CEA, CA 19-9 and CA50 for whom an initial diagnosis of metastatic poorly differentiated carcinoma was made. Suspecting EGCCS, he was treated as for a germ-cell tumor. While in treatment, he underwent residual orbital mass resection, and the histologic diagnosis was embryonal carcinoma based on alpha-fetoprotein immunoperoxidase staining. We discuss the rare location at diagnosis, the impressive increase in the commonly considered gastrointestinal markers that he showed, and the potential utility of these markers for such patients.

Adult↗
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A case of fatal food-borne septicemia: can family physicians provide prevention?

BACKGROUND: Vibrio vulnificus, a common bacteria found in undercooked seafood and seawater, is the leading cause of food-borne death in Florida. Fatal cases of V vulnificus infection have also been reported in most states. METHODS: The literature was searched using the key words "Vibrio vulnificus," "septicemia," "wound infections," "seafood," "immunocompromise," and "patient education." A case of fatal V vulnificus septicemia is described. RESULTS AND CONCLUSIONS: V vulnificus, part of the natural flora of temperate coastal waters and one of the most abundant microorganisms found in seawater, has been isolated from waters off the Gulf, Pacific, and Atlantic coasts of the United States. Infections in noncoastal regions have been traced to consumption of seafood derived from Gulf Coast waters. Seawater exposure and consumption of inadequately cooked seafood are routes most commonly associated with V vulnificus infection. Exposure to V vulnificus is life-threatening for chronically ill or immunocompromised patients, who are most likely to develop fatal septicemia. Currently a combination of doxycycline and intravenous ceftazidime is recommended treatment. Mortality rates from V vulnificus continue to be high in immunocompromised patients. Family physicians can help prevent this outcome by counseling high-risk patients.

Aged↗
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Blood technique.

Explore the source record for details and available documents.

Blood Transfusion↗
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[The epizootiology of tuberculosis of cattle in the Federal Republic of Germany].

Mycobacterial strains from different outbreaks of tuberculosis of cattle in Germany from 1996 to 2001 were differentiated by two molecular biological methods (Spoligotyping, RFLP IS6110). The causative agent was in one case Mycobacterium (M.) africanum, in 10 cases M. bovis and in 17 cases M. bovis ssp. caprae, respectively. The results of the molecular biological methods are discussed from the perspective of epizootiology and the particular importance of infections by M. bovis ssp. caprae emphasized. Direct contact of the animals, purchase from infected stocks, infected zoo animals and wildlife, as well as livestock handlers are discussed as possible sources of infection.

Animals↗
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Comparative metabolism of fenclorac in rat, dog, monkey, and man.

Fenclorac (alpha,m-dichloro-p-cyclohexylphenylacetic acid, diethylammonium salt), a new nonsteroidal anti-inflammatory agent, was rapidly and quantitatively absorbed from the gastrointestinal tract of rat, dog, monkey, and man following oral administration of a solution of 14C-labeled compound. Radiochromatography and mass spectrometry indicated that fenclorac was the principal component in plasma during both the absorption and elimination phases in all species. Small quantities of m-chloro-p-cyclohexylphenylglycolic acid metabolite were also present. Fenclorac and metabolite were confined primarily to the plasma phase of whole blood and were extensively bound to serum albumin. The plasma elimination half-time was species-dependent and varied from 1.6 hr in the rat to 6.5 hr in the dog. The principal tissues of distribution were liver, kidney, and small intestine. There was no significant accumulation or retention of drug or metabolites in any tissue compartment. Fenclorac was completely biotransformed prior to elimination in urine and bile. The major route of elimination was renal in man and monkey, and biliary in the dog. Enterohepatic recirculation of fenclorac metabolites was shown to occur in the rat. The major urinary metabolites were hydroxycyclohexyl analogs of fenclorac and m-chloro-p-cyclohexylphenylglycolic acid. There was no difference in metabolism and biological disposition of fenclorac in normal rats and rats with adjuvant-induced polyarthritis.

Administration, Oral↗
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The morphology of abdominal and inguinal cryptorchid testes in stallions: a light and electron microscopic study.

Eleven unilateral cryptorchid stallions, two to three years old, were castrated at Louisiana State University Veterinary Teaching Hospital. Five of these cryptorchid cases were abdominal and the rest were inguinal. This study was initiated to document the differences between the abdominal and inguinal equine cryptorchid testes. Specimens were obtained from the abepididymal side of each cryptorchid testes and processed for light and electron microscopic study. The cryptorchid testes were smaller than the scrotal testes, with the abdominal testes being one-fourth the size of the scrotal testes. Two of the abdominal testes had cysts filled with a straw-colored fluid. The seminiferous tubules of the abdominal testes were larger than those in the inguinal testes. The epithelial linings of the seminiferous tubules of the abdominal testes were vacuolated and did not contain more than two layers of undifferentiated cells. The interstitial collagen fibers of the abdominal testes were coarse and more abundant than those of the inguinal testes. The seminiferous tubules of the inguinal testes were smaller and contained many layers of epithelial cells at different stages of embryological differentiation, with scattered primordial germ cells. The necrotic, degenerative changes of the epithelial cells of the abdominal testes were distinct, while the inguinal testes had healthy cells at embryological arrest.

Animals↗