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Biomedical subjects

N J Murray

Publications and source records attributed to N J Murray.

10 recordsLinked to original sources

Infections during severe primary undernutrition and subsequent refeeding: paradoxical findings.

BACKGROUND: Our earlier uncontrolled observations during primary famine and subsequent refeeding did not suggest that severe undernutrition inevitably increases vulnerability to infection. Some infections appeared suppressed by famine but reactivated by refeeding. AIMS: To examine prospectively the occurrence of infections in a large cohort of primary famine victims before and during refeeding. METHODS: From 1973 to 1993, 4382 famine victims aged 14 or more with an estimated weight loss greater than 25% were weighed and examined for infection before and after one, two, three and four weeks of refeeding. In 137, serum C-reactive protein was measured in an effort to detect latent asymptomatic infections before and after two weeks of refeeding. Refeeding diets included wheat, sorghum, millet, ghee and milk powder. RESULTS: Mean weight loss +/- SD was 28.7 +/- 2.3%. Before refeeding overt infections were found in 4.9%, an incidence rising to 29.1% at two weeks of refeeding and declining after four. Those developing infections gained more weight at two weeks, 4.6 3 +/- 0.81 kg, than those never infected, 3.94 +/- 0.76 (p = < 0.001 t test). C-reactive protein levels confirmed the presence of latent infections before refeeding. CONCLUSIONS: Severe undernutrition can suppress certain infections, mostly those due to intracellular pathogens and especially P. falciparum. Refeeding reactivates suppressed infection and can increase vulnerability to certain new infections especially of viral origin. Those gaining weight the most rapidly may be at greatest risk. Refeeding with foods alien to local culture could play a role in reactivating latent infections. Our findings may be limited to severe undernutrition and not apply to lesser forms or secondary undernutrition in hospital patients. These studies were done during charitable provision of medical care to famine victims.

Adolescent↗

Conformational study of a salivary proline-rich protein repeat sequence.

Salivary proline-rich proteins have a repetitive primary structure particularly rich in the amino acids proline, glutamine and glycine. One of the biological roles of these proteins is to bind and precipitate polyphenols (vegetable tannins) present in the diet (e.g. tea, coffee, fruit, chocolate) neutralising their harmful actions which include nutritional loss, inhibition of gut enzymes and oesophageal cancer. Two peptides overlapping in sequence, corresponding to the mouse salivary proline-rich protein MP5 repeat sequence: QGPPPQGGPQQRPPQPGNQ and GPQQRPPQPGNQQGPPPQGGPQ have been synthesised and studied in H2O/(2H6)dimethyl sulphoxide (9:1, by vol.) using 1H-NMR spectroscopy. Low-temperature far-ultraviolet CD spectroscopy and NMR conformational parameters indicate that the peptides adopt an extended random coil conformation in solution. There is no evidence for a defined polyproline type II helix in the peptides, despite the high proline content. NMR data show that the trans-proline isomer predominates to at least 90%.

Amino Acid Sequence↗

Study of the interaction between salivary proline-rich proteins and a polyphenol by 1H-NMR spectroscopy.

The interaction between salivary proline-rich proteins and plant polyphenols (tannins) in the oral cavity and their subsequent precipitation influences the taste, texture and nutritional value of food; it is thought to be responsible for the astringency of many foods and beverages. To investigate the interaction, two-dimensional 1H-NMR studies have been carried out on the binding of a representative polyphenol, pentagalloyl glucose, to two synthetic peptides (19 and 22 residues in length) that are typical of the repeat sequence of mouse salivary proline-rich protein MP5. Intermolecular nuclear Overhauser effects and chemical shift changes show that the main binding sites on the peptides are proline residues together with the preceding amide bond and amino acid. The interaction is principally a hydrophobic association between a galloyl ring and the pyrrolidine ring face containing the C alpha proton, but secondary hydrogen-bonding effects help to stabilise the complex. Very similar interactions are seen for both peptides. The conformation of the peptides remains extended on binding. The chemical shift changes seen for many of the peptide protons can be fitted to a simple binding curve with dissociation constant of around 40 mM, but some protons show evidence of cooperative binding involving several galloyl groups. Higher concentrations of pentagalloyl glucose lead to a reduced off-rate from the complex and eventual precipitation which implies that precipitation is caused by a kinetic competition between aggregation and dissociation of the complex.

Amino Acid Sequence↗

Polyphenols, astringency and proline-rich proteins.

Recent, NMR and precipitation, studies of molecular recognition of proline-rich proteins and peptides by plant polyphenols are described and rationalized. The action of polysaccharides and caseins in the moderation of the astringent response, which is engendered by polyphenols present in foodstuffs and beverages, is described. The possible influence of plant cell wall glycoproteins on the process of lignification is discussed in the light of the observed affinity of phenolic substrates for prolyl residues in protein structures.

Amino Acid Sequence↗

Molluscum contagiosum and herpes simplex in Maasai pastoralists; refeeding activation of virus infection following famine?

An epidemic of molluscum contagiosum and oro-genital herpes simplex was observed in Maasai pastoralists of the Rift Valley. It coincided with a period of refeeding following famine, when the relief diet was different from normal milk fare. We propose that refeeding may be an important mechanism for activation of certain viral infections previously suppressed by famine.

Adolescent↗

Serum cholesterol, triglycerides and heart disease of nomadic and sedentary tribesmen consuming isoenergetic diets of high and low fat content.

1. The effects were examined of two approximately isoenergetic diets differing widely in saturated fat content on the levels of serum cholesterol and triglycerides of nomads and non-nomads in eastern Niger. Each person was also examined for clinical and electrocardiographic evidence of heart disease. 2. No significant differences could be found between serum cholesterol and triglyceride levels of 297 Anagamba nomad men consuming 73% energy as fat and 303 Kanouri sedentary men consuming 9% energy as fat. 3. Rheumatic heart disease was common in nomads and four possible cases of ischaemic heart disease were found in sedentary men only.

Adolescent↗

The effect of iron status of Nigerien mothers on that of their infants at birth and 6 months, and on the concentration of Fe in breast milk.

1. Within the limits of this study, neither maternal iron deficiency nor Fe-overload as measured at term appeared to affect the complement of Fe received by the foetus. 2. Infants feeding entirely on breast milk appeared to have normal Fe status 6 months postpartum regardless of the Fe status of the mother. 3. No relationship could be demonstrated between the Fe content of breast milk and the Fe status of the mother.

Anemia, Hypochromic↗

Diet and cerebral malaria: the effect of famine and refeeding.

In an outbreak of Plasmodium falciparum malaria following refeeding after famine cerebral malaria was restricted to children eating grain. Nomad children consuming a predominantly milk diet were free of this complication despite an equivalent incidence of uncomplicated malaria. Freedom of nomads from cerebral complications may be due to inhibition by the milk diet of rapid division of the parasite combined with delayed recovery after famine of T cell function.

Animals↗

Refeeding-malaria and hyperferraemia.

During the Central African (Sahelian) drought, attacks of falciparum malaria were common in patients and their relatives shortly after their arrival in a hospital in Eastern Niger. A prospective study of 72 adult patients not admitted for malaria and 109 accompanying relatives was undertaken to investigate this observation. 23 attacks occurred in patients and 51 in relatives, with a peak frequency five days after arrival. On arrival, parasitaemia was low but reached a maximum by five days. Serum-iron and percentage saturation of transferrin were moderately increased initially, rose dramatically within forty-eight hours with near maximum saturation, and were falling by the fifth day. It is suggested that the early hyperferraemia, apparently related to refeeding, led to rapid multiplication of existing parasites and attacks of malaria. The results of experimental malarial infection of Wistar rats, half of which had been given intramuscular iron, supported this hypothesis.

Adult↗

The ecological interdependence of diet and disease in tribal societies.

Observations among nomads suggest there is a strong ecological interdependence of diet and disease in tribal societies which favors survival of man. This relationship may be disrupted by changes in diet to conform to the highly productive technology of the West. Such changes may result in intensification of indigenous disease and in the transfer of disease characteristics of Western societies. To prevent these consequences, relief feeding and long-term attempts to upgrade nutrition should be carried out with traditional foods wherever possible.

Africa↗