The progressive pressor response to angiotensin in the rabbit

1. The threshold for any detectable rise of systemic arterial pressure during the prolonged intravenous administration of angiotensin to conscious rabbits was observed to be an infusion rate of 0·003-0·006 μg.kg^-1.min^-1.

2. At infusion rates between threshold and 0·04 μg.kg^-1.min^-1 the systemic arterial pressure rose progressively over a 3- to 7-day period to a plateau.

3. On stopping the angiotensin infusion the blood pressure fell rapidly back to its base line much faster than it rose during the infusion. The time taken to reach control values was approximately related to the duration of the infusion.

4. At infusion rates of about 0·05 μg.kg^-1.min^-1 the full rise of blood pressure developed within a few minutes, and could be sustained without change for many days. At higher rates the blood pressure diminished with time.

5. Diurnal fluctuations of blood pressure were often seen during prolonged infusions of angiotensin at low rates; and more rapid fluctuations of blood pressure over an hour or two were frequently encountered immediately after an infusion was turned off.

6. The possible role of angiotensin in producing chronic renal hypertension is discussed in the light of these observations.

     

The effects of alteration of CO2 and pH on intestinal blood flow in the cat

1. The effect of alteration of arterial blood pH on intestinal blood flow in the cat has been determined under conditions of constant perfusion pressure.

2. Arterial blood pH was altered over the range 7·12-7·70 by infusion of acid and alkali. When end-tidal CO₂ was held constant, there was no change in intestinal blood flow.

3. When arterial blood pH was altered over the range 7·19-7·55 by the administration of CO₂ at constant respiratory volume and rate, flow increased with increasing CO₂.

4. The intestinal vascular bed was less responsive to noradrenaline at pH 7·2 than at pH 7·6. The change in sensitivity was evident when end-tidal CO₂ was controlled and depended therefore on a change in hydrogenion concentration.

5. The dilator effect of CO₂ did not depend upon alteration of sensitivity to noradrenaline since it was seen after adrenergic blockade.

     

Renal contribution to thoracic duct lymph in dogs

1. The renal contribution to thoracic duct lymph was measured in seventeen anaesthetized fasting dogs by measurement of thoracic duct flow before and after renal arterial occlusion.

2. In eight experiments it was shown that thoracic duct flow and glomerular filtration rate were not significantly affected by the operation to expose the renal artery.

3. In three experiments occlusion of the renal vein, after release of arterial occlusion, resulted in a sudden increase in thoracic duct flow.

4. In animals infused with isotonic saline or dextrose (approximately 1 ml./min) the average values obtained for control thoracic duct flow, left renal flow and right renal flow were approximately 2·0, 0·7 and 0·3 ml./hr/kg body wt.: in non-infused animals these values were 1·4, 0·4 and 0·35 ml./hr/kg body wt. respectively.

5. Possible reasons for the apparently smaller lymph flow from the right than the left kidney, and the relationship between the renal contribution to thoracic duct flow and actual renal lymph flow are discussed.

6. Close correlation was found between control thoracic duct flow and body weight and between renal lymph flow and control thoracic duct flow.

     

Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

The maintenance of extracellular Na⁺ and Cl^- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na⁺ and Cl^- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg^-1·day^-1, sc) and progesterone (OVP, 1.7 mg·kg^-1·day^-1, sc). We assessed Na⁺ and Cl^- fractional excretion (FE_Na⁺ and FE_Cl^-, respectively) and renal and plasma catecholamine release concentrations. FE_Na⁺, FE_Cl^-, water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FE_Na⁺, FE_Cl^-, water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function.     

Carbamino compounds of haemoglobin in human adult and foetal blood

1. The carbamate (HbCO₂) concentration in oxygenated and deoxygenated human adult and foetal red blood cells was estimated at a constant pressure of carbon dioxide (P_CO2 = 40 mm Hg) and various pH values of the serum. The Donnan ratio for chloride and bicarbonate ions was used to calculate the bicarbonate concentration in the red cells. With this figure the carbamate concentration was calculated as follows:

[HbCO₂] = [Total CO₂] - [HCO^-₃] - [dissolved CO₂].

2. At a given pH value in the red cell deoxygenated foetal red cells contain more HbCO₂ than deoxygenated adult ones. Upon oxygenation (at constant pH) HbCO₂ drops in both types of erythrocytes to lower values than in deoxygenated cells. The fraction of `oxylabile carbamate' (-ΔHbCO₂/ΔHbO₂) at a red cell pH of 7·2 and a P_CO2 of 40 mm Hg is 0·117 in foetal and 0·081 in adult erythrocytes.

3. From the fraction of moles carbamate formed per Hb monomer (moles CO₂/mole Hb_i) K′_c and K′_z, the apparent carbamate equilibrium constants were calculated which can be used to estimate the carbamate concentration in normal adult and foetal blood.

4. The first apparent dissociation constant of carbonic acid is significantly higher in oxygenated (-log₁₀K′₁ = pK′₁ = 6·10) than in deoxygenated (pK′₁ = 6·12) adult red cells, whereas in foetal red cells the difference is smaller and statistically not significant.

5. For a given set of physiological conditions in arterial and mixed venous blood in respect to oxygen saturation, P_CO2 and pH, the fractional contribution of carbamino compounds of haemoglobin to the amount of carbon dioxide which is exchanged during the respiratory cycle was computed on the basis of the present results and found to be 10·5% in adult and 19% in foetal blood.

     

The release of acetylcholine from the spinal cord of the cat by antidromic stimulation of motor nerves

1. ACh was measured in the effluent from the perfused lumbosacral cord of the cat with or without stimulation of the central ends of the cut left sciatic and femoral nerves after section of the left dorsal roots.

2. In about 30% of the preparations ACh was obtained in the samples collected at rest (average 3·3 ng/min); the amount of ACh release was increased 1·3-9 times by stimulation of the peripheral nerves. The average amount of ACh collected during stimulation of the peripheral nerves at 5/sec was 6·9 ng/min. Antidromic motor nerve impulses responsible for the ACh release were likely to be only those in alpha motor fibres.

3. There was a depression in ACh release/stimulus as the stimulus frequency was increased more than 10/sec. Such changes in ACh release with various stimulus frequencies were correlated with depression in the response of Renshaw cells to excitation through motor-axon collaterals.

4. Amounts of ACh release during stimulation of the peripheral nerves at 5/sec were significantly increased for 1 or 2 min after a short tetanic stimulation of the nerves.

5. Intravenous injection of dihydro-β-erythroidine did not reduce the amount of ACh release produced by stimulation of the peripheral nerves.

6. It is concluded that antidromic impulses in alpha motor fibres liberate ACh from the presynaptic terminals at the central synapses on Renshaw cells.

     

The specific influence of carbon dioxide and carbamate compounds on the buffer power and Bohr effects in human haemoglobin solutions

1. Lymph from the lungs of lambs and sheep was found to enter both the right lymph duct and the thoracic duct. Right lymph duct flow was collected by constructing a venous sac, the venous tributaries of which were ligated but which the right lymph duct entered; thoracic duct flow was collected by cannulating the duct. Lymph from sites other than the lungs was excluded from the collections.

2. Measurements were made of the surface tension characteristics of lung extracts and of the liquid present in foetal lungs. These values were used together with gestational age and crown-rump length to designate the foetal lambs into mature and immature groups.

3. Lymph flow from the lungs averaged 0·99 ml./kg body wt./hr in immature foetal lambs, and 1·81 ml./kg/hr in mature foetal lambs before the start of ventilation. Lymph flow from the lungs of spontaneously delivered new-born lambs (mean age 51 hr) averaged 0·86 ml./kg/hr. In adult ewes right lymph duct flow averaged 0·11 ml./kg/hr and total lung lymph flow was estimated indirectly to be 0·33 ml./kg/hr. Calculated rates of protein flow in lung lymph (flow × protein concentration) were greater in foetal lambs than in adult sheep.

4. Total thoracic duct flow averaged 2·48 ml./kg/hr in immature foetal lambs, 5·30 ml./kg/hr in mature foetal lambs, 3·65 ml./kg/hr in new-born lambs, and 2·92 ml./kg/hr in adult ewes.

5. At the start of ventilation there was an increase in lymph flow from the lungs, which at 15-30 min reached a mean of 6·4 ml./kg/hr in mature lambs and 2·6 ml./kg/hr in immature lambs. At the same time the protein concentration of lymph decreased but the calculated protein flow increased.

6. The lungs of foetal lambs weighed more than the lungs of spontaneously delivered new-born lambs, and the difference could be accounted for by liquid which could be aspirated through the trachea of the foetal lamb. On ventilation of the lungs for 2 hr, without first allowing the escape of any lung liquid, lung weight measurements indicated that about 66% of the lung liquid had been taken up in mature lambs and about 50% in immature lambs.

7. It was concluded that the rate at which lymph is formed in the lungs is greater per kilogram body weight in foetal than in new-born lambs and greater in them than in ewes. The increase in lymph flow at the start of ventilation could account for the removal of about 40% of the liquid present in the lungs of the mature foetus and about 25% of the liquid in the lungs of the immature foetus.

     

The characteristics of spontaneous and evoked action potentials recorded from the rabbit''s uterine nerves

1. A method is described for recording in vivo the action potentials of afferent and efferent fibres in whole nerves supplying the rabbit's uterus.

2. Examination of these nerves under the light microscope and the electron microscope showed them to be composed almost entirely of non-myelinated fibres.

3. Two types of spontaneous action potential were observed; one travelled at about 4 m/sec and probably came from the myelinated fibres, the other travelled at 0·4-1·4 m/sec and certainly came from non-myelinated fibres.

4. The efferent fibre spikes were shown to be faster and higher than the spikes from uterine afferent fibres, but slower and smaller than spikes from broad ligament afferent fibres.

5. Apart from differences in conduction velocity and height, all spikes were basically similar, lasting about 1·5 msec. The height was related to the square of the velocity. Some more complex spikes were also observed.

6. The compound action potential evoked by stimulation of the uterine nerve had three peaks, conducted at 1·3, 0·8 and 0·6 m/sec, respectively, and thought to correspond to the fast afferent fibres, the efferent fibres and the slow afferent fibres, respectively. There were also some late peaks due to reflexion of the antidromic action potentials from the ganglion cells.

7. Stimulation of the hypogastric nerve also evoked a compound action potential in the uterine nerves. Stimulation of the pelvic nerves had no effect.

8. By means of ganglion blocking agents, the uterine ganglia were shown to lie in the pelvic plexus, peripheral to the hypogastric nerve, but central to the uterine nerves.

9. It is argued that the spontaneous action potentials came from individual fibres rather than Remak bundles, and that the recording technique used detected the activity of all but the smallest fibres.

     

The pH of brain extracellular fluid in the cat

1. The blood supply to the medulla was determined by the injection of indian ink via the vertebral arteries. Virtually the whole medulla was supplied by penetrating vessels from the ventral surface. The highest density of small arterioles and venules was found close to the roots of XII and on the ventrolateral surface.

2. The pH of extracellular fluid (pH_e.c.f.) was measured with pH microelectrodes of tip size 1-3 μm in cortex and medulla in seventeen cats, anaesthetized with pentobarbitone or a chloralose—urethane mixture. Parallel measurements were made of the pH of c.s.f. and plasma, the DC potential between plasma and brain and ventilation or phrenic nerve discharge.

3. In the majority of tests under steady conditions, the pH of e.c.f. was found to be lower than that of c.s.f. by between 0·03 and 0·08 units. No systematic pH gradients could be found to a depth of 5 mm beneath the surface of either medulla or cortex.

4. When plasma P_CO2 was altered, pH_e.c.f. changed with a latent period and speed of response related to the density of blood vessels. In vascular areas of the medulla and in the cortex, the latent period of 4 sec and the change of pH_e.c.f. coincided with changes in ventilation. Changes in pH_c.s.f. over the same areas were invariably slower.

5. CO₂ buffering capacities were in the order plasma > e.c.f. > c.s.f. Typical values were respectively, -2·2, -2·1 and -1·6.

6. The pH of e.c.f. was unaffected by the intravenous injection of H+ and only slowly by the injection of HCO₃-. Only up to a depth of 1 mm beneath the surface was pH_e.c.f. affected by superfusion of mock c.s.f. in the range 6·8-8·0 units. This response had a latent period of 2-3 min and was complete in 15 min.

7. The pH of e.c.f. fell with hypoxia after a latent period of > 1 min and if all vasosensory nerves had been cut, pH_e.c.f. was markedly affected by changes of blood pressure.

8. These results indicate that even under steady conditions, the pH of e.c.f. and c.s.f. is not identical, that pH_e.c.f. is more obviously affected by changes in P_{a, CO2} than pH_c.s.f. and that putative H+ sensors which drive respiratory neurones are likely to be similarly affected.

     

Transport of potassium at the blood—brain barrier

1. The pial surface of different regions of the central nervous system of the rabbit have been bathed with artificial cerebrospinal fluid (c.s.f.), containing different concentrations of potassium. The object has been to change the composition of the interstitial fluid with respect to this ion, where it is adjacent to subarachnoid c.s.f.

2. Two techniques, subarachnoid perfusion from the supracallosal space between the hemispheres to the cisterna magna and barbotage from the cisterna magna, have been used. If the artificial c.s.f. contains Evans Blue, the former procedure results in maximum staining of the pia and underlying nervous tissue of the pons-medulla and spinal cord. The latter procedure results in maximum staining of the medial and supero-lateral surfaces of the cerebral hemispheres, particularly anteriorly.

3. During subarachnoid perfusion at 0·06 ml./min with the potassium-free fluid, most regions of the brain took up significantly greater amounts of ⁴²K than was the case during perfusion with the fluids containing 3 and 10 m-equiv/l. For blue cerebral cortex, the tissue subjected directly to the inflowing fluid and showing the biggest differences, the ratios, c.p.m. per g brain/c.p.m. per ml. plasma, were 1·71 ± 0·12 (+44%), 1·19 ± 0·05 and 1·07 ± 0·08 (-10%) during perfusion with the fluids containing, 0, 3 and 10 m-equiv/l. respectively.

4. During barbotage, the uptake of ⁴²K into pons-medulla and spinal cord from blood plasma, the concentration in the latter being effectively kept near constant, was, at the end of 2 hr, greater when the fluid contained potassium, 0 m=-equiv/l. rather than 10 m-equiv/l. Thus the ratio, c.p.m per g brain/c.p.m. per ml. plasma was (0·99 ± 0·04 (+36%) as against 0·73 ± 0·05 for pons-medulla where the difference was greatest.

5. Simultaneous measurements of the entry of [¹⁴C]urea from blood to different regions of the central nervous system revealed no significant differences due to the differing concentrations of potassium imposed by either barbotage or subarachnoid perfusion. This appears to exclude a non-specific cause for the changes in ⁴²K uptake, an example of which might be a changing blood flow.

6. Reasons are given for supposing that the big increase in ⁴²K uptake due to the potassium-free fluid must be due to events occurring at the blood—brain barrier. This might be some form of interaction, possibly the single file effect, such that a low potassium concentration in the interstitial fluid potentiates ⁴²K influx across the blood—brain barrier. Alternatively it might be due to a low potassium concentration in this fluid greatly reducing active potassium movement from interstitial fluid to blood. The former explanation would conform neatly with the present results; but the latter would additionally be compatible with other evidence concerning the homoeostasis of potassium concentration in c.s.f. and the interstitial fluid of brain.

     

Validation of autoradiography for recognition of antigen-binding lymphocytes in blood and lymphoid tissues: quantitation and specificity of binding

Antigen-binding lymphocytes were recognized by their reaction with radioiodine labelled antigens such as flagellin and haemocyanin. Counts varied according to the antigen and species studied. For flagellin, counts in human blood of antigen-binding lymphocytes (mean ± 1 SD per 1000 lymphocytes) were 19·0±3·0, and in foetal thymus 18·2±5·0 and spleen 3·5±0·5. Results depended on contact time of cells with antigen, concentration of antigen, autoradiographic exposure, presence of natural antibody and antibody levels after immunization. Antigen-binding lymphocytes in blood were not antibody-producing cells. The specificity of the antigen-binding reaction was shown by exposing lymphocytes to 0·5 μg of two antigenically distinct flagellins; there was a 67–100% increase in the counts in contrast to the 20–45% increase on doubling the dose (0·5 μg to 1 μg) of flagellin from Salmonella adelaide. Cytophilic antibody as the cause of antigen binding was excluded.

The binding of flagellin to lymphocytes was prevented by anti-human IgM and light chain antisera, but not anti-human IgG sera. The binding of labelled flagellin was prevented by unlabelled flagellin but 100 times more was needed for blood lymphocytes than thymocytes. It is inferred that thymocytes, T cells, have considerably fewer receptors than most β lymphocytes detectable in blood.

Using standardized conditions, radiolabelled antigen binding provides a reproducible, immunologically specific and flexible technique allowing study of the nature and role of antigen-binding cells and cell surface receptors.

     

The velocity of lymph flow in the canine thoracic duct

1. The velocity and pattern of movement of lymph in the thoracic duct of anaesthetized and conscious dogs has been studied by observing the movement of droplets of ultrafluid lipiodol in the duct.

2. The velocity of flow when anaesthetized varied from 0·1-2·0 cm/sec, to 5·0 cm/sec when conscious.

3. The pattern of flow was affected by respiration and the cardiac cycle. Most movement occurred at the end of inspiration.

4. The duct of five autopsy preparations was perfused with saline to assess the volume and velocity of flow produced by the level of pressure gradients previously observed in the duct. These studies show that the small gradients (2-5 mmHg) observed during life are more than sufficient to produce the normal volume and velocity of flow measured. The mean resistance of the duct was 0·5 mmHg/ml. min.

     

Hemodynamic mechanisms of the attenuated blood pressure response to mental stress after a single bout of maximal dynamic exercise in healthy subjects

To determine the hemodynamic mechanisms responsible for the attenuated blood pressure response to mental stress after exercise, 26 healthy sedentary individuals (age 29 ± 8 years) underwent the Stroop color-word test before and 60 min after a bout of maximal dynamic exercise on a treadmill. A subgroup (N = 11) underwent a time-control experiment without exercise. Blood pressure was continuously and noninvasively recorded by infrared finger photoplethysmography. Stroke volume was derived from pressure signals, and cardiac output and peripheral vascular resistance were calculated. Perceived mental stress scores were comparable between mental stress tests both in the exercise (P = 0.96) and control (P = 0.24) experiments. After exercise, the systolic blood pressure response to mental stress was attenuated (pre: 10 ± 13 vs post: 6 ± 7 mmHg; P < 0.01) along with lower values of systolic blood pressure (pre: 129 ± 3 vs post: 125 ± 3 mmHg; P < 0.05), stroke volume (pre: 89.4 ± 3.5 vs post: 76.8 ± 3.8 mL; P < 0.05), and cardiac output (pre: 7.00 ± 0.30 vs post: 6.51 ± 0.36 L/min; P < 0.05). Except for heart rate, the hemodynamic responses and the mean values during the two mental stress tests in the control experiment were similar (P > 0.05). In conclusion, a single bout of maximal dynamic exercise attenuates the blood pressure response to mental stress in healthy subjects, along with lower stroke volume and cardiac output, denoting an acute modulatory action of exercise on the central hemodynamic response to mental stress.     

Cutaneous thermoreceptors in primates and sub-primates

1. Cutaneous thermoreceptors were examined electrophysiologically in primates (monkey, baboon) and in sub-primates (dog and rat) by recording from single units dissected from peripheral nerves.

2. Thermal stimuli were delivered from thermodes in contact with the skin.

3. Primate `cold' receptors had spot-like receptive fields and were found in both hairy and glabrous skin. The conduction velocities of the axons ranged from 0·6 to 15·3 m/sec.

4. The discharge from the primate receptors characteristically appeared in bursts with intervals of silence within the range temperatures of 18-40° C. Static and dynamic sensitivity curves were established, with maxima about 30° C.

5. Cold receptors in the lip of the dog had maximal sensitivity at 31-37° C. The axons were myelinated with conduction velocities less than 20 m/sec.

6. `Warm' receptors, with maximal sensitivity at 40° C and non-myelinated axons, were abundant in the scrotal nerve of the rat. The `cold' receptors had maximal responses at 23-28° C.

7. The `spurious' thermoreceptor behaviour of slowly adapting mechanoreceptors is described and the way in which they may distort integrated potential records from whole nerves is analysed.

     

Distribution of chylomicrons and albumin in dog kidney

1. Under specified experimental conditions the distribution space of labelled chylomicrons in the kidney was 13·8 ± 0·9 ml./100 g. tissue. The assumption is supported that this provides a measure for the quantity of intravascular plasma constituents.

2. Values for red blood cells and albumin distribution spaces were 5·2 ± 0·6 and 20·2 ± 1·0 ml./100 g tissue, respectively, in the whole kidney. The ratio of tissue haematocrit over simultaneous arterial haematocrit averaged 0·56. The extravascular albumin fraction amounted to about 31·0% of the total albumin in the whole kidney.

3. A statistically significant correlation was demonstrated between osmotic urine/plasma (U/P) ratios (within the approximate limits of 0·6-1·8) and quantities of extravascular albumin in the medulla.

     

Die Ausscheidungsfunktion der Niere nach schneller Infusion kochsalzhaltiger und kochsalzfreier Lösung

Summary Renal function was investigated in unanesthetized dogs during rapid expansion of blood volume and extracellular fluid volume by rapid infusion of isotonic saline and hypotonic dextrose solutions. The typical excretion pattern could be divided into 3 Phases (Phase 1: 1.–30. min, Phase 2: 31.–90. min and Phase 3: 91.–300. min after begin of infusion). Phase 1 was characterized by a fast rise of glomerular filtration rate and renal plasma flow and an increase in urine volume and sodium excretion in both groups. In Phase 2 and 3, the influence of GFR and RPF was reduced, and a study of the excretion patterns suggests predominance of hormone mechanisms (ADH and Aldosterone) probably activated by volume regulatory or osmoregulatory stimuli.The rise in GFR and RPF may be caused by reduction of blood viscosity combined with a rise in arterial blood pressure. A reflex vasodilatation of renal vessels may tentatively be attributed to a rise in central venous pressure.

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Mit 5 Textabbildungen

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Mit Unterstützung der Deutschen Forschungsgemeinschaft und des European Office, Air Research and Development Command.     

Elastic constants of the human lens capsule

1. A technique is described whereby the elasticity of the human lens capsule has been determined at birth and throughout life. This technique requires three separate determinations: (a) thickness; (b) stress and strain; (c) Poisson's ratio; (a) the capsule was clamped between accurately perforated ground glass plates and its thickness determined by noting the change in depth of focus between Latex spherules adhering to its upper and lower surfaces; (b) the undisturbed capsule was then placed in a specially designed glass distension apparatus and the relationship between volume and pressure recorded when it was distended with isotonic saline. The permeability of the capsule was also measured; (c) in some cases Poisson's ratio was determined by measuring the change of thickness of the capsule and the height to which it rose when distended with isotonic saline at different pressures. An apparatus was designed for this purpose.

2. The average thickness of the anterior capsule increases from birth until about the 60th year but thereafter it decreases slightly.

3. Poisson's ratio was about 0·47 for both cat and human capsule, and no significant variations with age in human capsule could be detected.

4. Corrected volume pressure curves obeyed Hook's law almost to the point of capsule rupture.

5. In childhood Young's Modulus of elasticity is about 6 × 10⁷ dyn/cm² and decreases to 3 × 10⁷ dyn/cm² at 60 and 1·5 × 10⁷ dyn/cm² in extreme old age.

6. The ultimate tensile stress was 2·3 × 10⁷ dyn/cm² in young capsules and 0·7 × 10⁷ dyn/cm² in old ones. The maximum percentage elongation was 29 per cent and independent of age.

7. The implications of these findings are discussed in relation to

(a) the mechanical properties of the lens capsule;

(b) the ageing of the lens capsule and basement membranes; and

(c) the decrease in elasticity of the lens capsule as a cause of presbyopia.

     

The metabolism of autologous IgM and 19S rheumatoid factor in rheumatoid arthritis

The turnover of autologous preparations of radio-iodine labelled IgM and 19S rheumatoid factor was studied and compared in patients with severe rheumatoid disease. The IgM was isolated by block electrophoresis and column chromatography. 19S rheumatoid factor was isolated by a combination of euglobulin precipitation, column chromatography, and absorption onto and acid-elution from solid aggregated IgG.

Ten studies were made in seven patients, five with IgM, and five with 19S rheumatoid factor. In two patients the turnovers of 19S rheumatoid factor and IgM were studied simultaneously.

The turnover of IgM was similar to that reported for normal subjects and patients with other diseases: fractional catabolic rate 0·14–0·18, plasma and whole body T_½ 3·7–6·5 days, with 65–77% intravascular localization. The absolute catabolic rate for IgM was elevated (8–60 mg/kg/day).

The turnover of 19S rheumatoid factor isolated from serum was comparable in fractional catabolic rate (0·15–0·19) plasma and whole body T_½ (3·9–6·0 days) and intravascular localization (62–88%). No evidence of rapid catabolism of the `immune' elimination type was obtained.

     

Human erythrocyte anion permeabilities measured under conditions of net charge transfer

1. The permeability of the human erythrocyte to anions has been measured under conditions of net charge transfer: for Cl^- and HCO₃^- ions, at 37° C, this permeability is 5 orders of magnitude too small to account for the rate of the electroneutral anion exchange which is responsible for the chloride, or Hamburger, shift.

2. The method is an indirect one in which the ionophore, valinomycin, is used to increase the erythrocyte K⁺ permeability: in the absence of permeant cation externally, the rate of the resulting K⁺ efflux may be limited by the slowness of the accompanying anion efflux, allowing the true anion permeability to be estimated.

3. The average Cl^- permeability estimated in ACD-stored erythrocytes (seven experiments) and erythrocytes from fresh blood (two experiments) was 2·1 × 10^-8 cm/sec at 37° C and pH 7·4: this may also be expressed as a Cl^- conductance of about 1·0 × 10^-5 Ω^-1 cm^-2. The apparent activation energy for net efflux of Cl^- was found to be 3·9 kJ/mole (16·4 kcal/mole).

4. In fresh cells, the ratios of Cl^-, HCO₃^-, Br^- and I^- permeabilities (or conductances) were 1:0·8:1·5:5. The three halide ions follow Eisenman's Sequence I, representing a binding site of low field strength.

     

Early changes in the forearm circulation following transient increase of local external pressure

1. The pressure at the surface of a segment of forearm enclosed in a plethysmograph was abruptly raised from atmospheric level to +40 mm Hg, held at the new level for 4 sec, and abruptly dropped to atmospheric level.

2. Forearm circumference (V_f) equivalent to the volume of a small segment of forearm, was monitored with a mercury-in-rubber strain gauge. Pressure was measured in the cylinder (P_p) in veins exposed to external compression (P_{v, e}), and in the radial artery exposed to compression (P_ra).

3. Forearm blood flow was measured by venous occlusion plethysmography before, and after, release of external compression. There was, on average, over the 3rd and 4th second after release of pressure, a 2·4-fold increase of inflow, as compared with resting level.

4. By the 15th second after release of compression, forearm blood flow had returned to its previous resting level.

5. The increase in blood flow after compression appears to be due to active reduction in vascular resistance, for refilling of the arteries and arterioles would be completed before the increased flow was recorded; venous backflow can be excluded, and the pressure difference for flow (arterial minus venous) is virtually unchanged.