Biomedical subjects

K D Bloch

Publications and source records attributed to K D Bloch.

79 records · Page 5Linked to original sources

PubMed1986

Atrial natriuretic factor: assessment of its structure in atria and regulation of its biosynthesis with volume depletion.

Atrial natriuretic factor (ANF) is a polypeptide that has been isolated from mammalian atrial tissue with potent natriuretic, diuretic and spasmolytic properties. Details of its biosynthesis, cleavage, storage and release are not yet fully defined. Using sequence-specific anti-peptide antisera in immunocytochemical and radioimmunoassay studies, we demonstrated the presence in atrial granules of sequences corresponding to both the large molecular weight ("prohormone") form of ANF and the carboxyterminal peptide believed to be responsible for its biological activity. However, a peptide sequence spanning the proposed site of cleavage of the "signal peptide" from preproANF was undetected. In volume-depleted rats, a 28% decrease in the relative concentrations of atrial ANF mRNA was observed as compared to that of controls (P less than 0.01). There was, however, no significant difference observed between the two groups of animals with respect to atrial levels of ANF, as measured by radioimmunoassay. We conclude from these studies that proANF, but not preproANF, is stored in atrial granules. The concentration of stored ANF remains constant in volume-depleted rats despite a 28% reduction in ambient levels of ANF mRNA. The physiologic significance of these findings is discussed.

Animals↗

PubMed1986

Bartter's syndrome and the atrial natriuretic factor gene.

We investigated whether the gene for atrial natriuretic factor, a recently discovered peptide hormone with potent natriuretic, diuretic, and vasorelaxant properties, was pathogenetically linked to an uncommon but well-defined fluid and electrolyte disorder, Bartter's syndrome. Restriction fragment length polymorphisms in the atrial natriuretic factor gene were sought in a large kindred with six of 23 family members being affected. A Bgl II polymorphism, identified in two of 40 (5%) apparently normal subjects, was found in one of two first-generation family members. This polymorphism was also present in five of seven unaffected second-generation siblings but in only three of six affected siblings. The failure of the absence or the presence of the polymorphism to cosegregate with the disease clearly indicates that in this kindred, the gene for atrial natriuretic factor is not linked to Bartter's syndrome.

Atrial Natriuretic Factor↗

PubMed1986

Atrial natriuretic peptide transcription, secretion, and glomerular receptor activity during mineralocorticoid escape in the rat.

The mechanisms that mediate renal "escape" from the sodium-retaining effects of mineralocorticoids are incompletely understood. This study was undertaken to determine whether atrial natriuretic peptide (ANP) may play a role in the escape phenomenon. Immunoreactive ANP in rat plasma increased 2.5-fold above baseline values at 12 and 24 h after a single depot injection of desoxycorticosterone acetate in oil and returned to baseline thereafter. In addition, specific pre-pro-ANP messenger RNA content in rat atria was significantly elevated as early as 12 h after mineralocorticoid administration and remained elevated at 24, 48, and 72 h, indicating a prompt and sustained increase in ANP biosynthesis. Renal glomerular ANP receptor density was down-regulated appropriately with rising plasma ANP levels, and receptor affinity was unchanged. Thus, mineralocorticoid administration in the rat is a powerful stimulus for ANP release and for atrial myocyte ANP synthesis, which suggests a potential role for this hormone in overriding mineralocorticoid-induced renal sodium retention.

Animals↗

PubMed1985

Biosynthesis and secretion of proatrial natriuretic factor by cultured rat cardiocytes.

Rat atrial natriuretic factor (ANF) is translated as a 152-amino acid precursor preproANF. PreproANF is converted to the 126-amino acid proANF, the storage form of ANF in the atria. ANF isolated from the blood is approximately 25 amino acids long. It is demonstrated here that rat cardiocytes in culture store and secrete proANF. Incubation of proANF with serum produced a smaller ANF peptide. PreproANF seems to be processed to proANF in the atria, and proANF appears to be released into the blood, where it is converted by a protease to a smaller peptide.

Amino Acid Sequence↗

PubMed1984

Nucleotide sequences of the human and mouse atrial natriuretic factor genes.

Mouse and human atrial natriuretic factor (ANF) genes have been cloned and their nucleotide sequences determined. Each ANF gene consists of three coding blocks separated by two intervening sequences. The 5' flanking sequences and those encoding proANF are highly conserved between the two species, while the intervening sequences and 3' untranslated regions are not. The conserved sequences 5' of the gene may play an important role in the regulation of ANF gene expression.

Animals↗

PubMedDate not supplied

Aberrant expression of the constitutive endothelial nitric oxide synthase gene in Alzheimer disease.

Neuritic pathology is a major neuroanatomical correlate of dementia in Alzheimer disease (AD). Nitric oxide (NO) is linked to neuritic growth and synaptic plasticity. Expression of one of the enzymes responsible for NO synthesis, the constitutive endothelial NO synthase (ceNOS), was investigated in brains of AD and Down syndrome patients using RNase protection assays, in situ hybridization, and immunocytochemistry. In end-stage AD, ceNOS expression was reduced in cortical neurons, and the enzyme was aberrantly translocated to membranes of proliferated swollen or collapsed neuritic processes. In addition, ceNOS expression was strikingly increased in glial cells characterized mainly as protoplasmic (Type 2) astrocytes, which are responsible for maintaining the structural and functional integrity of cell processes in the CNS. In Down syndrome, similar abnormalities emerged by the third decade, preceding the cognitive decline and establishment of CERAD criteria for AD, indicating that aberrant ceNOS expression occurs early in the course of neurodegeneration. The results suggest that aberrant ceNOS translocation and gene regulation may have important roles in the pathogenesis of AD neuritic pathology.

Adult↗

PubMedDate not supplied

Molecular studies of the atrial natriuretic factor gene.

The molecular biology of human atrial natriuretic factor was studied. A cloned rat cDNA probe was used to analyze tissue for the synthesis of atrial natriuretic factor, and the human gene was identified and sequenced. Nucleotide sequence comparison of human and rodent atrial natriuretic factor genes suggests regions that are critical for regulated expression of this cardiac hormone.

Amino Acid Sequence↗