Biomedical subjects

O Rosen

Publications and source records attributed to O Rosen.

11 recordsLinked to original sources

PubMed1992

C-reactive protein (CRP) peptides inactivate enolase in human neutrophils leading to depletion of intracellular ATP and inhibition of superoxide generation.

The nature and the biochemical mechanism of inhibition of neutrophil membrane-associated oxidative metabolism by two synthetic peptides p77-82 and p201-206 (amino acid sequences Val-Gly-Gly-Ser-Glu-Ile and Lys-Pro-Gln-Leu-Trp-Pro respectively, from the primary amino acid sequence of C-reactive protein) have been ascertained. Preincubating neutrophils for 15 min with 50 microM of p77-82 or p201-206 resulted in superoxide generation by opsonized zymosan stimulated neutrophils being inhibited by 34 +/- 2% (P less than 0.005) and 29 +/- 2% (P less than 0.005) respectively. With a 60-min preincubation period 6.25 microM of p77-82 or p201-206 was effective in inhibiting this superoxide generation by 12 +/- 2% (P less than 0.01) and 10 +/- 1% (P less than 0.01) respectively. Neither peptide inhibited neutrophil arachidonic acid release, transmembrane potential or transductional events preceding superoxide generation. Inhibition of neutrophil functions was found to be due to the ability of each peptide (50 microM) following a 15-min preincubation period to inhibit both neutrophil glycolysis and ATP generation by approximately 30%. The inhibition of ATP generation and glycolysis in neutrophils is attributable to the ability of these peptides to inhibit uncompetitively the glycolytic enzyme enolase. Using purified enolase the relative Ki values for p77-82 and p201-206 were 27 and 19 microM respectively. Inhibition of neutrophil function by the peptides is concluded to be due to effective interference of neutrophil energy metabolism.

Adenosine Triphosphate↗

PubMed1991

Changes in soluble carbonic anhydrase activity in response to maturation and NH4Cl loading in the rabbit.

Maturation and systemic acidosis are two factors that stimulate urinary acidification. Proton secretion, CO2 handling, and some metabolic processes are facilitated by cytosolic carbonic anhydrase (CA). The activity of this enzyme in kidney, red blood cells (RBCs), and liver could be regulated in response to acid-base perturbations or maturation. Therefore, we investigated the effects of maturation and NH4Cl acid loading on soluble CA hydratase activity in RBCs, kidneys, and livers of female New Zealand White rabbits during three stages of maturation (neonatal, 4 wk, and adult). Total RBC CA activity doubled with maturation but did not increase after NH4Cl loading. There was substantial interindividual variation in the amount of CA I related activity. In the kidney we found intrinsic cortical CA II activity to be more than twice that in the outer medulla, which was more than twice that in the inner medulla. CA activity doubled with maturation in the cortex and increased by 70% in the outer medulla. Twenty hours after an NH4Cl load there was a 50% increase in renal cortical CA activity in 4-wk-old rabbits, but a comparable increase in cortical CA activity was only seen after 3-5 days of NH4Cl loading in adult animals. In the liver a third of cytosolic CA activity was acetazolamide resistant, presumably CA III, which doubled with maturation. Chronic NH4Cl loading in adult animals induced an almost 60% increase in hepatic acetazolamide-sensitive CA activity (mostly CA II). These data show that in the rabbit there is a renal corticomedullary gradient in soluble CA activity (mostly CA II), with significant activity in the inner medulla. Maturation induced total CA activity in the inner medulla. Maturation induced total CA activity in RBCs, CA II activity in kidney cortex and outer medulla, and CA III in the liver. Finally, CA II activity in kidney cortex and liver appeared to be regulated in response to some conditions of NH4Cl loading.

Acetazolamide↗

PubMed1991

Physicians' perceptions of the role of clinical dietitians are changing.

We surveyed a selected group of physicians to determine their opinions regarding appropriate activities and educational background for hospital dietitians. Questionnaires were mailed to 401 physicians listed in the yellow pages of the 1988 San Jose/Santa Clara, Calif, telephone directory. Physicians were chosen from nutrition-related specialties such as cardiology, endocrinology, and gastroenterology. Questionnaires were returned by 123 (30%) physicians. Most physicians viewed dietitians as contributing members of the health care team. However, they believed that the physician should be responsible for ordering therapeutic diets. Most physicians (98%) agreed that one of the most important duties of the dietitian is to assure patient satisfaction with food served. Physicians (94%) also believed that presenting current nutrition information to hospital personnel is an important activity. Counseling patients was an area most physicians (99%) thought should be included in the educational background of dietitians. Sixty percent of the physicians indicated that it is important for the dietitian to understand blood and urine laboratory values. These results indicate that the perceived status of hospital dietitians by physicians has improved since earlier studies.

Attitude of Health Personnel↗

PubMed1990

Peptides generated from C-reactive protein by a neutrophil membrane protease. Amino acid sequence and effects of peptides on neutrophil oxidative metabolism and chemotaxis.

We have recently provided evidence that C-reactive protein (CRP) could act as an up-regulatable substrate for membrane-associated neutrophil serine protease(s). The resultant degradation of CRP yielded small soluble bioactive peptides that inhibit many of the proinflammatory functions of activated neutrophils and could oppose the tissue destructive potential of these cells. We report on the reverse phase HPLC separation of the small TCA-soluble peptides obtained when CRP is degraded with nonstimulated or PMA-stimulated neutrophils and purified neutrophil membranes. The amino acid sequence of seven peptides isolated from the CRP digest has been ascertained and synthetic peptides homologous to these sequences have been synthesized. Three of the synthetic peptides corresponding to residues 201-206 (CRP-III), 83-90 (CRP-IV), and 77-82 (CRP-V) of the intact protein were identified to significantly inhibit superoxide production from activated neutrophils at 50 microM whereas CRP-III and CRP-V in addition inhibited neutrophil chemotaxis at this concentration. These peptides act additively and their action likely involves the signal transduction pathways for neutrophil activation.

Amino Acid Sequence↗

PubMed1990

Thiolysis of the 3-nitro-2-pyridinesulfenyl (Npys) protecting group. An approach towards a general deprotection scheme in peptide synthesis.

The hydroxylic side-chain functional groups of serine, threonine, hydroxproline and tyrosine, the alpha and epsilon-amino moieties of lysine and the thiol group of cysteine were masked by the 3-nitro-2-pyridinesulfenyl (Npys) protecting group. Deprotection was mildly affected by thiolysis with either 2-mercaptopyridine and 2-mercaptomethyl imidazole (O- and N-Npys) or with 3-mercaptoacetic acid and 2-mercaptoethanol (S-Npys). Thiolysis was monitored spectrophotometrically and was completed in a rather short time. Incorporation of the Npys group into a whole and single thiolyzable deprotection scheme is suggested.

Chemical Phenomena↗

PubMed1989

The prevalence of high insertion of scrotum, hydrocele and mobile testis in the newborn infant (36-42 weeks gestation).

The prevalence of some minor abnormalities of the male genitalia was studied in 271 boys born over a period of 2 months. The scrotal insertion on the ventral side of the penis was determined in an objective manner by measuring the ratio of the ventral and dorsal length of the unstretched penis. A scrotal insertion ratio of less than 0.48 defined high insertion of the scrotum which was found in 2.7% of our newborn infants. This anatomical finding has an important clinical significance for the performance of early circumcision. The prevalence of hydrocele in all male newborn infants was 57.9%. Extravaginal (communicating) type was present in 86% of all infants, intravaginal (noncommunicating) in 9.5%, while both types of hydrocele in the same neonate was observed in 4.5%. The relatively high frequency of mobile testes (22%) is of interest. The natural history of this entity is not fully understood and the question of follow-up remains open.

Anthropometry↗

PubMed1989