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Biomedical subjects

D H Williams

Publications and source records attributed to D H Williams.

206 records · Page 12Linked to original sources
PubMedDate not supplied

The "n' effect in molecular recognition.

The cooperativity which exists in crystal melting and many biological molecular recognition phenomena arises from extended arrays of weak interactions. We present a correlation between the melting temperature of a crystal and the intermolecular energy (which is evident only when compounds possessing several or many internal rotors are excluded). The correlation is used as the basis for a model of crystal melting which is capable of estimating the melting temperature of crystals. This model provides the basis for an understanding of the sharpness of the crystal melting transition for organic and inorganic substances. The cooperativity illustrated by the extended arrays of weak interactions, or the "n' effect, is extended to analogous order/disorder transitions in biological systems, such as the "melting' of DNA and RNA duplexes, providing insights into the physical properties of these structures.

Crystallization↗
PubMedDate not supplied

A mass spectrometric method for the identification of novel peptides in Xenopus laevis skin secretions.

The peptides secreted by the South African frog Xenopus laevis were screened systematically using a strategy based on fabms. Hplc of crude and Sephadex G-10 chromatographed secretions showed that many more peptides were present in these secretions than those previously identified, i.e., xenopsin, caerulein, TRH, and PGLa. Fractions from the hplc were analyzed directly by fabms to determine the molecular weights of these novel peptides. Subsequent analyses, using a combination of fabms, manual Edman degradation, enzymatic digestions, and amino acid analyses identified the partial and sometimes complete sequences of these peptides which had molecular weights ranging from 700-2700. Many peptides with structural features that are often indicative of biological activity, e.g., C-terminal amides and pyroglutamic acid, were readily identified by fabms. In some cases, molecular weight data combined with partial sequence data was sufficient to identify peptides as originating from spacer regions in the precursors to xenopsin, caerulein, and PGLa.

Amino Acid Sequence↗
PubMedDate not supplied

Why are secondary metabolites (natural products) biosynthesized?

We adopt the definition of a natural product as a substance that has no known role in the internal economy of the producing organism. The literature abounds with conflicting views for the existence of such natural products. We propose that all such structures serve the producing organisms by improving their survival fitness. We argue that this conclusion is necessitated by the fact that natural products are normally complex structures, whose biosynthesis is programmed by many kilobases of DNA. If it were otherwise, the pressures of Darwinian natural selection would have precluded the expenditure of so much metabolic energy in their construction and the development of such complexity. We further conclude that a natural product improves the producer's survival fitness by acting at specific receptors in competing organisms. Current studies of natural products interacting with receptors support this view, in terms of both the sophistication of the molecule/molecule recognition and the mechanistic details of physiological action. By the application of Occam's razor and general weaknesses of other hypotheses, these other hypotheses are rejected. It is a consequence of our proposal that natural product/receptor interactions of sophistication comparable to enzyme/substrate interactions will be commonplace. Additionally, structures that are candidates to interact with known receptors (e.g., double helical DNA) can on occasion be suggested by inspection of the structures. A range of evidence to support the general conclusions is presented.

Anti-Bacterial Agents↗
PubMedDate not supplied

Increased collateral arterial and venous endothelial cell turnover after renal artery stenosis in the dog.

Renal artery stenosis was induced in dogs and collateral arterial formation assessed by serial angiography and histology. Endothelial cell turnover was estimated by radioautography in five normal and five collateral-forming kidneys 18-39 days following stenosis with tritiated thymidine. Normal arterial endothelial labeling was 0.1% with a highly significant (p less than 0.0005), 55-fold increase in endothelial labeling in arterial collateral vessels. A smaller but statistically significant increase in the labeling index was also found in endothelial cells of the renal vein, from a normal of 0.065% to 0.4% (p less than 0.005). An excellent correlation was found between endothelial cell labeling in small arteries and the renal veins (r = 0.97; p less than 0.01). A marked increase in epithelial cell labeling of the ureters draining the stenotic kidneys was also evident (p less than 0.005). Thus, collateral vessel development is characterized by active DNA synthesis in cellular elements, and a humoral factor is implicated in the vascular response.

Angiography↗
PubMedDate not supplied

The influence of twelve weeks of aerobic training on the blood lipids of middle-aged men.

Lipoprotein profiles revealed a significant increase in total cholesterol between trained and control groups and an increase of HDL-C in both groups after exercise. There were no significant differences in resting cholesterol levels, nor in LDL-C after exercise in both groups. The results of the study suggest that improvement in work capacity as a result of training is not necessarily accompanied by changes in the lipid profile.

Adult↗