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Biomedical subjects

R M Schultz

Publications and source records attributed to R M Schultz.

At least 217 records · Page 12Linked to original sources

Elevated threshold for thyrotropin suppression in congenital hypothyroidism.

Five infants with congenital hypothyroidism were found to have persistently elevated levels of serum thyrotropin (TSH) for six to 24 months after administration of adequate doses of thyroxine. In these infants, the hypothalamic-pituitary threshold for TSH suppression by thyroxine seems to be unusually high. These observations suggest that serum TSH levels should not be the sole criterion for evaluating adequacy of thyroid hormone replacement during the initial months of therapy for congenital hypothyroidism.

Congenital Hypothyroidism↗

Ribonucleoside metabolism by mouse oocytes: metabolic cooperativity between the fully grown oocyte and cumulus cells.

Ribonucleoside uptake and metabolism were studied in mouse oocytes arrested at dictyate and metaphase II, with or without attached cumulus cells. Uptake of uridine and guanosine decreased after meiotic maturation, whereas that of adenosine and cytidine remained unaltered. Dictyate oocytes free of cumulus cells (denuded) phosphorylated all of the radiolabeled ribonucleosides. Little radiolabeled ribonucleoside-5'-triphosphate was found. This is in contrast to the early mouse embryo, which rapidly converts ribonucleosides to the 5'-triphosphate (Daentl and Epstein, "71; Clegg and Piko, "77). Following meiotic maturation, the major metabolite present when metaphase II oocytes were cultured with cytidine or uridine was the ribonucleoside, whereas the 5'-monophosphate was still the major species for oocyte cultured with guanosine or adenosine. Ribonucleoside uptake was increased and the distribution of phosphorylated metabolites was different for cumulus-enclosed dictyate oocytes compared to their denuded counterparts. This increase in uptake and alteration in metabolite distribution was not observed for cumulus-enclosed metaphase II oocytes. These results are discussed in terms of gap junction-mediated metabolic cooperatively between the cumulus cells and the fully grown oocyte and the possible role this type of cell-to-cell interaction may serve during oocyte growth.

Adenosine↗

E-type prostaglandins and interferons: yin-yang modulation of macrophage tumoricidal activity.

It is proposed that nonimmunologic microenvironmental stimuli such as interferons and E-type prostaglandins (PGE) can modulate macrophage tumoricidal activity in local tissue immunity. These agents act as "local hormones" since they have a high catabolic rate and short biologic half-life in serum. Interferons provide a common pathway for induction of cytotoxic macrophages by diverse agents such as viruses, bacterial lipopolysaccharides, and double-stranded RNA, and PGE act as a biologic "resistor" to control expression of activated macrophage tumor killing. Since both PGE and interferons are secretory products of activated macrophages, it is envisioned that they could act in negative and positive feedback mechanisms to intrinsically modify macrophage functional activity. Finally, tumors may defend themselves from attack by activated tumoricidal macrophages by releasing high levels of PGE that subvert local macrophage activity.

Animals↗

Evidence for hemiacetal formation between N-acyl-L-phenylalaninals and alpha-chymotrypsin by cross-saturation nuclear magnetic resonance spectroscopy.

N-Acetyl-L-phenylalaninal exists predominantly in its hydrated form in aqueous solution, but the aldehyde and not the hydrate is shown by nuclear magnetic resonance (NMR) spectroscopy to be the effective inhibitor of alpha-chymotrypsin. NMR spectroscopy also indicates that the initial alpha-chymotrypsin-N-acetyl-L-phenylalaninal complex is in equilibrium with a hemiacetal formed between the aldehyde and the active site serine residue. The rate of the latter equilibration is slow on the NMR time scale but the hemiacetal can be detected by cross-saturation NMR spectroscopy. N-Benzoyl-L-phenylalaninal is a more potent inhibitor of alpha-chymotrypsin than the N-acetyl derivative and both the formation of the enzyme-inhibitor complex and the hemiacetal are slow on the NMR time scale, but the hemiacetal in the enzyme can be detected by cross-saturation NMR spectroscopy. The N-acyl-L-phenylalaninals also bind to N-methylhistidinyl-57-alpha-chymotrypsin, but clear evidence for hemiacetal formation was not obtained by cross-saturation NMR spectroscopy either because the hemiacetal was not formed or more probably because the rate of dissociation was slow compared with the rate of relaxation of the hemiacetal proton. The dissociation constant of N-benzoyl-L-phenylalaninal to dehydroalaninyl-195-alpha-chymotrypsin was found to be high relative to the dissociation constant to native alpha-chymotrypsin, supporting the NMR evidence that a hemiacetal with the Ser-195 is formed on association of N-benzoyl-L-phenylalaninal with alpha-chymotrypsin.

Acetals↗

Effect of macrophage activation by immunoadjuvants on serum levels of lysosomal hydrolases in mice.

The effect of pyran copolymer, injected into mice bearing the M109 Madison lung carcinoma, on serum concentrations of lysozyme, beta-glucuronidase, and N-acetyl-beta, D-glucosaminidase was studied and compared with that of other immunoadjuvants. Increases in lysozyme levels ranging from 50 to 100% were observed after injection of pyran, BCG and Bru-Pel; increases in the levels of the other enzymes were less consistent. Other immunoadjuvants were less effective in raising serum concentrations of lysosomal enzymes. The findings were correlated with the results of previous studies on macrophage activation and antineoplastic action produced by these immunoadjuvants and suggest that serum levels of lysozyme can serve as indices of these effects.

Acetylglucosaminidase↗

Effects of adriamycin and cyclophosphamide treatment on induction of macrophage cytotoxic function in mice.

The effects of i.p. and s.c. Adriamycin and cyclophosphamide treatment of BALB/c x DBA/2F1 mice were studied alone and in combination with immunotherapeutic agents, pyran copolymer and Bacillus Calmette-Guérin, on macrophage cytotoxic ability, As assessed by direct viable cell counts of MBL-2 leukemia cells, both Adriamycin and cyclophosphamide produced growth-inhibitory macrophages. This function after s.c. cytostatic treatment peaked at Day 1 and decreased progressively, attaining normal control values by Day 6. When adjuvants, such as pyran and B. Calmette-Guérin, were administered i.p. simultaneously with s.c. Adriamycin or cyclophosphamide, adjuvant-induced cytotoxic function was not markedly affected. A better knowledge of the influence of cytostatic agents alone or combined with immunoadjuvants on macrophage cytotoxic ability may be useful in designing more effective chemoimmunotherapy protocols.

Animals↗