Biomedical subjects
Publications and source records attributed to J Herman.
A patient with type 3 Gaucher disease is described with a novel genotype, D399N/R463C, established by DNA sequencing. This patient was previously reported as having genotype N370S/R463C. This communication now establishes that no patients reported with mutation N370S have the neuronopathic forms of Gaucher disease and has important implications for genetic counseling.
At 23 months of age, one of a pair of monozygotic twins with radiographic unilateral hyperlucent lung was evaluated by radionuclide ventilation/perfusion pulmonary studies, which revealed a ventilation/perfusion mismatch of an entire lung. This twin died, and autopsy revealed pulmonary arterial thrombosis and histological changes compatible with homocystinuria, which was subsequently shown to be present in the surviving twin as well. A ventilation/perfusion lung scan of the surviving twin revealed multiple ventilation/perfusion mismatched defects, suggestive of pulmonary embolism. The presenting manifestation of homocystinuria in these patients was the pulmonary thrombotic disease. Neither twin had any other stigmata of homocystinuria at the time of initial presentation.
The human MAGE3 gene is expressed in a significant proportion of tumors of various histological types, but is silent in normal adult tissues other than testis and placenta. Antigens encoded by MAGE3 may therefore be useful targets for specific antitumor immunization. Two antigenic peptides encoded by the MAGE3 gene have been reported previously. One is presented to cytolytic T lymphocytes (CTL) by HLA-A1, the other by HLA-A2 molecules. Here we show that MAGE3 also codes for a peptide that is presented to CTL by HLA-B44. MAGE3 peptides containing the HLA-B44 peptide binding motif were synthesized. Peptide MEVDPIGHLY, which showed the strongest binding to HLA-B44, was used to stimulate blood T lymphocytes from normal HLA-B44 donors. CTL clones were obtained that recognized not only HLA-B44 cells sensitized with the peptide, but also HLA-B44 tumor cell lines expressing MAGE3. The proportion of metastatic melanomas expressing the MAGE3/HLA-B44 antigen should amount to approximately 17% in the Caucasian population, since 24% of individuals carry the HLA-B44 allele and 76% of these tumors express MAGE3.
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The presence of the maternal warm antibody in pregnancy should not be ignored. As there is risk of both maternal and fetal anemia, both patients need to be followed for the development of such. Serial complete blood counts in the mother and treatment if significant fetal anemia develops should be considered. Serial amniocentesis and nonstress testing should be part of any management plan in the presence of a maternal warm antibody.
Red cell oxygen affinity, red cell nucleoside triphosphate (NTP) levels and blood oxygen-carrying capacity were determined for male, nonpregnant and pregnant female, and fetal garter snakes Thamnophis elegans exposed to hypoxia (5 % oxygen) and hyperoxia (100 % oxygen). Male and nonpregnant female snakes were maintained under these conditions for up to 3 weeks and exhibited an apparent maximal change in oxygen affinity after 14 days of hypoxia and hyperoxia. Red cell NTP levels decreased and oxygen affinity increased with exposure to hypoxia, while exposure to hyperoxia promoted an increase in red cell NTP concentrations and a decrease in red cell oxygen affinity in the males. Hyperoxia-exposed nonpregnant females did not show a significant change in oxygen affinity. After 14 days of hypoxia, the pregnant females showed an increase in red cell oxygen affinity which was associated with a decrease in red cell NTP concentration and in the molar ratio of NTP/hemoglobin relative to normoxic controls. Fourteen days of hyperoxia did not result in a change in oxygen affinity of red cells from the pregnant female, but did promote a slight increase red cell NTP concentrations. The blood parameters of fetuses from females exposed to hypoxia or hyperoxia did not differ from those of normoxic control fetuses. The fetuses of females exposed to hypoxia suffered greater mortality, appeared less developed and had a lower average wet mass than the fetuses of normoxic- and hyperoxic-exposed females. Neither hypoxia nor hyperoxia altered the oxygen-carrying capacity of the blood in any group of snake.
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Antibodies to Neospora caninum were detected in 5 (10%) of 52 coyotes from Texas. Antibodies to Toxoplasma gondii were detected in 32 (62%) of 52 samples from these same coyotes. Four (80%) of the 5 coyotes that were seropositive for N. caninum also had antibodies to T. gondii. Nineteen (37%) of the coyotes did not have antibodies to either parasite. Three coyote pups were inoculated with the brains from mice infected with 3 strains of N. caninum originally isolated from dogs. None of the pups developed neosporosis or excreted N. caninum oocysts in their feces. The pups developed anti-N. caninum antibody titers of > or = 1:800 but did not develop antibodies to T. gondii. Results of this study indicate that antibodies to T. gondii are more common than antibodies to N. caninum in coyotes. Additionally, young coyotes appear to be resistant to experimental N. caninum infection.
During the period between August 1995 and February 1996 at the Second Surgical Clinic of the Faculty Hospital in Olomouc 12 retroperitonescopic lumbar sympathectomies were performed on account of different indications. The authors present an elaborate technique of access into the retroperitoneum and their own technique of lumboscopic sympathectomy. The success of the method was evaluated clinically and by histological evidence of sympathetic ganglia in the collected material. Retroperitoneoscopic lumbar sympathectomy is considered a gentle and safe method which can be used also in other patients where the risk of open surgery would be excessive.
Chemical packs are recent innovations in the delivery of dry heat. Because these delivery systems do not have any mechanism for verifying temperature during application, research to determine their safety seems warranted. The purpose of this study was to measure the skin temperature of adults during a 30-minute application of the MediHeat adult heating pad (MH-AHP). Seventy-seven subjects received a 30-minute application of the MH-AHP to their backs while lying in both supine and prone positions. The mean skin temperature in both positions was 101 degrees F. There were significant differences, however, in minimum and maximum skin temperature between positions. Subjects in the prone position had significantly higher maximum skin temperature and significantly lower minimum skin temperature than subjects in the supine position. It is possible that the prone position allows for more air flow over the MH-AHP and that more heat was generated causing the higher maximum temperature. This explanation does not account for the lower minimum temperature. There were no significant differences in perception of heat between the positions at either 5 minutes or 30 minutes. Findings suggest that caution is necessary when applying heating devices that depend on air circulation for heat generation.
The medical profession's tendency to equate 'the greatest good for the greatest number' with proactive care is here challenged; and the idea that we can always get more for our money with an ounce of prevention than with a pound of cure is scrutinized from an ethical point of view. It is suggested that preventive measures are often exempted from such scrutiny because they make medicine appear selfless and are aimed at the postponement of death-always an urgent matter. Indeed, our screening efforts can assume the proportions of a crusade against life's natural termination and we must make sure that they do not emanate from the needs of medical science for publicity and funding. The costs of what has been called 'healthism', something that has almost become a new morality, are frequently underestimated and its side effects overlooked. There are conditions for which effective palliation, sometimes enormously expensive, is available. The automatic assumption that money spent on such palliation could be better used for, say, immunization, is not warranted.
Peptide MAGE-1.A1 is a nonamer derived from protein MAGE-1 that can associate with the HLA-A1 molecule. It was shown previously to be recognized by an antitumor cytolytic T lymphocyte (CTL) clone derived from the blood of melanoma patient MZ2. We derived two other anti-MAGE-1.A1 CTL clones from different blood samples of the same patient and compared the fine specificity of recognition of the three CTL by testing them on variant MAGE-1.A1 peptides incorporating different amino acid substitutions. The epitopes recognized by the CTL proved to be different. While modifications of residues at positions 5, 6, or 7 in the antigenic peptide affected recognition by the three CTL, each of the modifications of residues at positions 1, 4, or 8 affected recognition by one CTL only. The sequences of both the alpha and beta chains of the T cell antigen receptor of the three CTL were completely different. The results indicate a long-lasting diversity in terms of fine specificity and of T cell antigen receptor structure in the repertoire of antitumor CTL derived from the blood of a melanoma patient and directed against a defined tumor antigen.
We have identified an antigen recognized on a human melanoma by autologous cytolytic T lymphocytes. It is encoded by a gene that is expressed in many normal tissues. Remarkably, the sequence coding for the antigenic peptide is located across an exon-intron junction. A point mutation is present in the intron that generates an amino acid change that is essential for the recognition of the peptide by the anti-tumor cytotoxic T lymphocytes. This observation suggests that the T-cell-mediated surveillance of the integrity of the genome may extend to some intronic regions.
Since an inverse relationship between waking and REM sleep eye movements (EMs) has been found with respect to frequency, amplitude and direction of EMs, we evaluated variations in the percentages of horizontal rapid eye movements (REMs) during REM sleep after having increased rightward saccades during waking by means of a unilateral tachistoscopic visual test administered prior to sleep. In another condition subjects were given the same 4 h testing condition prior to sleep, the only difference being that they were instructed not to move their gaze; therefore only "attentional movements" were possible. This condition served as a control for the role of oculomotor activity in the complementary relationship between waking and REM sleep eye movements. The actual increase of rightward saccades during waking resulted in a significant decrease of rightward REMs. This effect has been observed only in the condition in which rightward eye movements were increased and it is specific for REMs of amplitude similar to those which were increased during waking by the lateralized test.