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Biomedical subjects

H J Schmidt

Publications and source records attributed to H J Schmidt.

At least 19 recordsLinked to original sources

A cotton rat model of effectors of immunity to respiratory syncytial virus other than serum antibody.

A model for studying effectors of immunity to respiratory syncytial virus (RSV) was developed. Paris of inbred cotton rats (Sigmodon hispidus) were joined surgically using the technique of parabiosis. One week later, one animal of each pair was primed intranasally with a small volume of RSV suspension. Fourteen days after priming, both animals of each pair were bled for determination of serum neutralizing antibody titers, and challenged intranasally with a standard dose of RSV suspension. Single, unprimed cotton rats were challenged concomitantly and served as controls. Four days after challenge, all animals were sacrificed for virus titration of nasal tissues and lungs. Parabiosed cotton rats were surgically separated at varying intervals between priming and challenge (days 7, 9, 12, or 14 after priming) or were kept joined until sacrificed (day 18). Significant transfer of nasal and pulmonary immunity from primed to unprimed parabionts began 9 days after priming, gradually increasing through 18 days. Resistance to RSV challenge in spite of low levels of serum neutralizing antibody suggests that non-antibody immunologic mediators were responsible for the transferred immunity. Evidence is presented for three broad categories of RSV immunologic effectors: systemic, local with a transient systemic phase, and local without a systemic phase. These categories are now amenable to further study using the described model.

Animals

Occurrence of fragmented 16S rRNA in an obligate bacterial endosymbiont of Paramecium caudatum.

The phylogenetic position of Caedibacter caryophila, a so far noncultured killer symbiont of Paramecium caudatum, was elucidated by comparative sequence analysis of in vitro amplified 16S rRNA genes (rDNA). C. caryophila is a member of the alpha subclass of the Proteobacteria phylum. Within this subclass C. caryophila is moderately related to Holospora obtusa, which is another obligate endosymbiont of Paramecium caudatum, and to Rickettsia. A 16S rRNA targeted specific hybridization probe was designed and used for in situ detection of C. caryophila within its host cell. Comparison of the 16S rDNA primary structure of C. caryophila with homologous sequences from other bacteria revealed an unusual insertion of 194 base pairs within the 5'-terminal part of the corresponding gene. The intervening sequence is not present in mature 16S rRNA of C. caryophila. It was demonstrated that C. caryophila contained fragmented 16S rRNA.

Animals

Pheromone 4 gene of Euplotes octocarinatus.

We have cloned and sequenced a 1.7 kb macronuclear chromosome encoding the pheromone 4 gene of Euplotes octocarinatus. The sequence of the secreted pheromone is preceded by a 42 amino acid leader peptide, which ends with a lysine residue. The sequence coding for the leader peptide contains information for a putative signal peptide and is interrupted by a 772 bp intron as shown by comparison with a cDNA clone. A 64 bp intron and a 145 bp intron interrupt the sequence coding for the secreted pheromone. The three introns contain typical 5' and 3' splice junctions and a putative branch point site. The small introns have a low GC content. The large intron has a GC content similar to that of the pheromone 4 gene exons. The amino acid sequence of pheromone 4, deduced from both the genomic DNA and the cDNA of pheromone 4, shows that the secreted pheromone consists of 85 amino acids. One of its amino acids is encoded by a UGA codon. Since it has been shown for pheromone 3 of E. octocarinatus that UGA is translated as cysteine, it is assumed that the UGA codon encodes cysteine in pheromone 4 as well. The 164 bp noncoding region upstream of the leader peptide is AT-rich and contains an inverted repeat capable of forming a stem-loop structure with a stem of 11 bp. The 151 bp noncoding region at the 3' end of the chromosome contains a putative polyadenylation sequence and an inverted repeat. The macronuclear molecule is flanked by telomeres and carries the pentanucleotide motif TTGAA, located at a distance of 17 nucleotides from the telomeres. This motif has been suggested to be involved in the formation of macronuclear chromosomes.

Amino Acid Sequence

Immunotherapy of respiratory syncytial virus infection in cotton rats (Sigmodon fulviventer) using IgG in a small-particle aerosol.

To determine whether aerosolized IgG can be used effectively in the treatment of respiratory syncytial virus (RSV) infections, cotton rats were infected intranasally with RSV and treated 3 days later with human IgG containing anti-RSV antibodies delivered in a small-particle aerosol. Pulmonary histology and virus titers were determined 24 h after IgG treatment. A single 15-min exposure to aerosolized IgG did not exacerbate pulmonary pathology and effected a 50-fold reduction in pulmonary virus titer (2.95 vs. 4.67 log10 geometric mean pfu/g for untreated controls, P < .001), which was comparable to that effected by intranasally instilled IgG (50 mg/kg) (3.24 vs. 4.67 log10 geometric mean pfu/g for controls, P < .001). A 15-min exposure to aerosolized ribavirin (20 mg/mL) was not effective in reducing pulmonary virus. This study suggests that aerosolized IgG could be useful in the treatment of RSV lower respiratory tract infections and that it compares favorably with ribavirin.

Administration, Intranasal

Cecal vitamin bezoar formation inducing abdominal discomfort.

OBJECTIVE: To document a case of cecal lecithin-vitamin B12 bezoar formation inducing abdominal discomfort. DESIGN: Case study. SETTING: 500-bed, community teaching hospital. PATIENT: 81-year-old man with a history of multiple abdominal surgeries who presented with a chief complaint of abdominal pain. Flat plate X-ray of the abdomen revealed multiple capsule-shaped objects lodged in the cecum. INTERVENTIONS: Catharsis with bisacodyl, magnesium citrate, NaCl 0.9%; dissolution with heated, dilute barium administered rectally in conjunction with external manipulation; laparotomy. MAIN OUTCOME MEASURES: None planned; dissolution or transit of bezoar through gastrointestinal tract desired outcome. RESULTS/DISCUSSION: Classification of bezoars and treatment discussed in relation to this case report. CONCLUSIONS: Medicinal agents have been implicated in bezoar formation. Treatment options have included: cathartics, heated solvent enemas, and external manipulation and surgery.

Abdominal Pain

Two introns in the pheromone 3-encoding gene of Euplotes octocarinatus.

The portion of the pheromone 3 (Phr3)-encoding gene (phr3) of Euplotes octocarinatus, corresponding to secreted Phr3 was isolated using the polymerase chain reaction and oligodeoxyribonucleotide primers flanking the Phr3-encoding cDNA. Unexpectedly, the sequence analysis revealed that this gene is interrupted by two introns with lengths of 63 bp and 72 bp. These introns belong to the class of nuclear pre-mRNA introns and contain typical 5'- and 3'-consensus sequences, as well as unique features. Our findings constitute the first example of introns in any Euplotes species and the first case of multiple introns in hypotrichous ciliates. In ciliates such as Euplotes, the macronucleus is the transcriptionally active nucleus. It develops from a micronucleus in a process which involves chromosome breakage and the elimination of up to 95% of the micronuclear genome. The existence of the introns in the macronuclear version of phr3 shows that, in spite of this extensive elimination, some noncoding sequences are nevertheless retained in the macronucleus of hypotrichous ciliates. It was recently discovered by Meyer et al. [Proc. Natl. Acad. Sci. USA 88 (1991) 3758-3761] that the Phr3-encoding cDNA contains three in frame TGA triplets coding for cysteine. The genomic sequence of phr3 confirms this finding.

Amino Acid Sequence

UGA is translated as cysteine in pheromone 3 of Euplotes octocarinatus.

Pheromone 3 mRNA of the ciliate Euplotes octocarinatus contains three in-frame UGA codons that are translated as cysteines. This was revealed from cDNA sequencing and from plasma desorption mass spectrometry of cleaved pheromone 3 in connection with pyridylethylation of the fragments. N-terminal sequence analysis of carboxymethylated protein confirmed this conclusion for the first of the three UGA codons. Besides UGA the common cysteine codons UGU and UGC are also used to encode cysteine. UAA functions as a termination codon. No UAG codon was found. In connection with results reported for other ciliates, this suggests that the role of the classic termination codons had not yet been established when the ciliates started to diverge from other eukaryotes.

Amino Acid Sequence

[Acute multifocal placoid pigment epitheliopathy with inflammatory CSF findings. A special form of borreliosis?].

A 24-year-old woman with acute multifocal placoid pigment epitheliopathy in both eyes had no signs or symptoms other than the impaired vision. Visual evoked potentials demonstrated prolonged latency. Lumbar CSF showed inflammatory changes. Serum antibody titres against Borrelia burgdorferi were markedly elevated. Cortisone treatment was without success, but intravenous penicillin quickly brought about improvement in vision. Borrelia infection may thus have been the cause of the multifocal placoid pigment epitheliopathy.

Acute Disease

Changes in sensitivity to the odor of androstenone during adolescence.

While it has been reported that most, if not all, very young children are able to detect the odor of 5 alpha-androst-16-en-3-one (androstenone), approximately 40-50% of human adults cannot detect its odor. The present study focused on changes in sensitivity to androstenone during adolescence, which may account for this discrepancy. Sensitivity to androstenone was determined in 247 subjects aged 6 to 50. There was a significant increase in the number of males anosmic to androstenone between 9-14 and 15-20 years of age, and a significant increase in threshold with age among males able to detect the odor. We infer that a smaller percentage of females than males becomes anosmic to the odor of androstenone during development, and those able to detect it apparently show a decrease in threshold with age. No age-related changes were observed in tests of pyridine or d,l-beta-phenylethylmethylethylcarbinol (PEMEC).

Adolescent

Characterization of Caedibacter endonucleobionts from the macronucleus of Paramecium caudatum and the identification of a mutant with blocked R-body synthesis.

Cytology, DNA and host-symbiont relationships of x-like endosymbionts from Paramecium caudatum are described. The symbionts (Caedibacter caryophila, sp. nov.) live in the macronuclei of their hosts. They confer the killer trait upon their hosts and appear well adapted to their endonucleobiotic way of life. R bodies (proteinaceous ribbons associated with killing) are produced, but differ significantly from any of the four R-body classes previously described. C. caryophila and their R bodies were isolated. DNA was extracted from purified symbionts and used to demonstrate that one P. caudatum line harbors a natural mutant which is deficient in R-body production. Melting studies indicate a GC content of 34.6%. No sequence homology between the C. caryophila DNA and the coding sequence for type 51 R-body production was observed. C. caryophila is parasitic, causing the death of its hosts in starving cultures.

Animals

Adult-like odor preferences and aversions in three-year-old children.

Previous studies of young children have failed to demonstrate adult-like odor preferences in children less than 5 years old. To test whether these results may have been due to inappropriate methods or to stimulus sets that were too limited in range to capture discriminations, a forced-choice procedure embedded in a simple game was used to contrast 3-year-olds' (n = 16) and adults' (n = 17) hedonic reactions to 9 odorants. Subjects indicated liking an odor by pointing to one puppet and disliking an odor by pointing to another puppet. Analyses revealed essentially the same pattern of preferences in both groups. In general, the odorant was a much better predictor of its hedonic quality than was the age of the subject. However, children and adults did differ in their ratings of some odors, and response patterns indicated that children may be more sensitive than adults to some odorants (e.g., the steroid androstenone). These data indicate that the predominant view that adult-like odor preferences and aversions do not exist until between 5 and 7 years of age must be reevaluated.

Adolescent

[Spontaneous lysis of acute Leriche syndrome].

Usually, obstructions of the terminal aorta require surgery involving an aortobifemoral bypass, especially if they occur with acute signs and symptoms, the clinical pattern of these signs being very marked. The authors report on a case where an extensive obstruction of the lumbar aorta and of the pelvic vessels finally dissolved without on-target therapeutic intervention via an obviously spontaneous lysis.

Aged