The ten-year experience of the Palo Alto Veterans Affairs Home-Based Primary Care Program.
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Biomedical subjects
Publications and source records attributed to M R McBride.
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To determine whether neurophysiological taste responses are different in young and old rats, recordings were made from the whole chorda tympani nerve which innervates taste buds on the anterior tongue. Fischer 344 male and female rats in three age groups were studied: 5 to 7 months, 23 to 25 months, and 29 to 32 months. Chemical stimuli included single concentrations of five salts, two acids, sucrose and quinine hydrochloride, and concentration series of the five salts. Neural response magnitudes were expressed as ratios relative to the NaCl(0.1M) response. Substantial neural responses were obtained to all chemicals at all ages. Response ratios for NH4Cl and sucrose, however, increased significantly with age; ratios for MgCl2 and citric acid decreased. Ratios for HCl decreased when data from either sex were analyzed separately. Shapes of response/concentration functions for NaCl, but not other salts, also differed with age. In general, though, the magnitudes of all age-related differences were small and neural recordings demonstrate that the peripheral taste system functions well in old age.
We have modified an SLM 4800 fluorometer to allow continuous measurement of fluorescence polarization. The modifications included construction of simple mechanical and electronic accessories which allowed polarizer position to be program-controlled by an HP 9815 calculator. With these modifications we were able to follow the interaction of the fluorescent lipid analog 1-acyl-2-(N-4-nitrobenzo-2-oxa-1,3-diazole)-aminododecanoyl phosphatidylcholine (I) with Naja-naja venom phospholipase A2 (PLA2) (E.C.3.1.1.4). Upon addition of aliquots of PLA2 containing up to 85 ng protein to a cuvette containing 1-2 microM I, the total measured polarization decreased linearly with time for at least 1000 s. Concomitant analyses of equivalent incubation mixtures and analyses of the contents of the cuvette after incubation and collection of fluorescence data revealed time-dependent formation of N-4-nitrobenzo-2-oxa-1,3-diazole-aminododecanoic acid (II). The decrease in total measured polarization was accelerated by Ca2+ and inhibited by EDTA. These data suggest that PLA2 activity in Naja-naja venom can be measured rapidly at low concentrations of both enzyme (0.01 microgram protein) and substrate (1 microM). Since this technique can be used to collect polarization data over time intervals as short as 4 s, it should be possible to measure the early changes in polarization during the interaction of fluorescent probes with proteins or membranes.
Neurochemical studies were performed on synaptosomal membranes from cats with GM1 or GM2 gangliosidosis to examine possible mechanisms of neuronal dysfunction in these disorders. The basic hypothesis tested was that deficient ganglioside catabolism causes increased ganglioside content of synaptosomal plasma membrane which in turn disrupts normal function. Fluidity characteristics of synaptosomal membranes were examined using fluorescence polarization. Results showed markedly reduced membrane fluidity in both GM1 and GM2 gangliosidosis. These results were supported by a second study which revealed that isolated synaptosomal membranes of GM1 gangliosidosis cats had a 24-fold increase in total ganglioside content caused predominantly by excess GM1, a 2.3-fold increased cholesterol content, and a 1.4-fold increased phospholipid content. Finally, kinetic analysis of synaptosomal plasma membrane Na+,K+-ATPase from cats with GM1 gangliosidosis showed negligible differences in kinetic parameters compared with controls. Thus, the enzyme appeared protected from the global membrane changes in fluidity and composition. These observations provide evidence for a pathogenetic mechanism of neuronal dysfunction in the gangliosidoses while demonstrating protection of certain vital functional components, such as Na+,K+-ATPase.
The development of sucking response was investigated in 30 clinically normal infants from 1 or 5 minutes postbirth until their first feeding 4 hours later. Maximum sucking pressures were measured with a research nipple attached to a portable electronic suckometer. Mean suction (negative pressure) began at 5 Torr at birth, peaked at 103 Torr at 90 minutes, and decreased thereafter to 65 Torr at 4 hours. Expression (positive pressure) began at 12 Torr, rose to 29, and decreased to 25. Mean expression pressures correlated with feeding scale scores, r = +.44(24); p less than .025, but suction pressures did not, r = +.26(24); p less than .1. Normative data were gathered on 10 additional stabilized newborns who had been fed twice successfully. Suction pressures were 96 Torr on Day 1, and 103 Torr on Day 2; expression pressures were 25 and 24 Torr, respectively. These pressures approximate those recorded in newborns between 1 and 2 hours postbirth.
To determine whether touch acuity is altered in individuals with maturity-onset diabetes, tactile thresholds on the pad of the index finger of 32 diabetic and 27 nondiabetic subjects were compared. A set of modified Von Frey hairs was used to present touch stimuli in a forced-choice tracking procedure that controls for subject response bias. The mean tactile threshold of diabetic patients was significantly higher than that of nondiabetic subjects, although the difference between the two groups is small. Within the diabetic group, decreased tactile acuity was associated with a longer duration of disease diagnosis, presence of insulin therapy, and low-digit temperature. However, reported presence or absence of peripheral sensory symptoms (tingling, numbness, etc.) in diabetic patients did not relate to touch thresholds. The small but significant increase in touch threshold that was observed in diabetic individuals may provide an early indication of sensory neuropathy. Further use of threshold determinations will contribute to our understanding of sensory changes that accompany diabetes.
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