Influence of physiologic hyperglucagonemia on basal and insulin-inhibited splanchnic glucose output in normal man. To evaluate the effects of physiologic hyperglucagonemia on splanchnic glucose output, glucagon was infused in a dose of 3 ng/kg per min to healthy subjects in the basal state and after splanchnic glucose output had been inhibited by an infusion of glucose (2 mg/kg per min). In the basal state, infusion of glucagon causing a 309 +/- 25 pg/ml rise in plasma concentration was accompanied by a rapid increase in splanchnic glucose output to values two to three times basal by 7-15 min. The rise in arterial blood glucose (0.5-1.5 mM) correlated directly with the increment in splanchnic glucose output. Despite continued glucagon infusion, and in the face of stable insulin levels, splanchnic glucose output declined after 22 min, returning to basal levels by 30-45 min. In the subjects initially receiving the glucose infusion, arterial insulin concentration rose by 5-12 muU/ml, while splanchnic glucose output fell by 85-100%. Infusion of glucagon causing an increment in plasma glucagon concentration of 272 +/- 30 pg/ml reversed the inhibition in splanchnic glucose production within 5 min. Splanchnic glucose output reached a peak increment 60% above basal levels at 10 min, and subsequently declined to levels 20-25% below basal at 30-45 min. These findings provide direct evidence that physiologic increments in plasma glucagon stimulate splanchnic glucose output in the basal state and reverse insulin-mediated inhibition of splanchnic glucose production in normal man. The transient nature of the stimulatory effect of glucagon on splanchnic glucose output suggests the rapid development of inhibition or reversal of glucagon action. This inhibition does not appear to depend on increased insulin secretio.


Arterial wall lesions after pulmonary embolism, especially ruptures and aneurysms. During an histological study of pulmonary thromboembolism, arterial wall splits, many associated with saccular microaneurysms, were observed in association with emboli or their fibrous residue. Other aneurysmal lesions, non-inflammatory focal medial necrosis, and medial scars were also seen in a few cases. The nature of the arterial rents indicates that they arose by mechanical splitting after acute stretching of the artery at the time of embolic impaction. Saccular aneurysms then developed in some. Impaction could also have caused the foci of medial necrosis while the medial scars could represent healed former necrosis of rupture. Though the observed incidence of lesions was relatively low, this seems to be due to their small sizes and the sampling inherent in conventional histological analysis. It is concluded that arterial splits are probably a common effect of pulmonary embolism and often give rise to small aneurysms.


Development of germinal centres in the spleen in infants related to birth and unexpected death. The development of germinal centres in the spleen has been estimated in a series of 266 children dying in hospital and 205 children presenting as unexpected death in infancy. The prevalence of germinal centres in the spleen increases rapidly after birth. The percentage of Malpighian bodies showing germinal centres in the spleen is greater in all categories of our classification of death in children dying unexpectedly at home when these are compared with hospital deaths. It is concluded that the children presenting as unexpected death in infancy show no evidence of any deficiency in cellular immunological response and may well have been subjected to increased or precocious antigenic stimulation.


Carcinomas and carcinoid tumours of the appendix in a district general hospital. In a retrospective series of 40 appendiceal tumours occurring over a 10-year period, 30 were carcinoid tumours of classical histological pattern, five were adenocarcinomas, and two were tumours intermediate in pattern between carcinoid and carcinoma. The remaining three tumours were secondaries from primary colonic tumours. The implications of the findings are discussed.


Effect of methotrexate therapy in psoriatics on the Ito cells in liver biopsies, assessed by point-counting. To evaluate the relationship, both quantitative and qualitative, between the Ito cells and methotrexate (MTX) therapy Ito cells were studied by light microscopy in 1 mum toluidine blue stained sections and by electron microscopy in 24 pairs of Menghini needle biopsies before and after MTX therapy of 24 consenting patients with severe psoriasis. Light microscopy showed a statistically significant increase in pathological findings (P less than 0-05) and in the number of Ito cells and their size (P less than 0-0001) after MTX therapy. It was not possible to show a statistically significant correlation between the increase in the number of Ito cells and the cumulative dose of MTX. Ultrastructural analysis of Ito cells showed no marked difference from pre to post-MTX specimens. The fibrosis and cirrhosis seen after MTX therapy in some liver biopsies from psoriatics and the post-MTX increase in the number of Ito cells direct attention to the possible role of Ito cells as fibroblast precursors.


Computerization of a large antenatal serology service. A computer scheme for a large antenatal serology service is described. A primary request form (for mother, father or child) has been developed. Standard reports are produced by the computer and are issued with a tear-off slip which should accompany subsequent specimens. Complicated reports are made by special letter. An instruction booklet is issued to all users. Information on patients and clinically significant antibodies is held in a special computer file and is regularly updated. The system provides an efficient and reliable day-to-day service and readily accessible data for retrospective research. A brief note on the computer elements of the system is provided.


Anisocytosis and the C-1000 Channelyzer in macrocytic anaemia. Red cell anisocytosis as assessed using the Coulter Channelyzer C-1000 showed an increase with progressive anaemia in 25 patients with macrocytosis due to B12 and/or folate deficiency. In deficiency of a single factor, the degree of anisocytosis increased with progressive anaemia. In five cases with B12 and folate deficiency combined, anisocytosis was markedly increased out of proportion to the degree of anaemia present. Iron stores were also reduced in four of these cases. It is suggested that objective measurement of anisocytosis is of early diagnostic value in the assessment of multiple haematinic factor deficiency, for example, in macrocytic anaemia associated with malabsorption states and unexpected multiple deficiency states.


Regional quality control.

Regional quality control. Methods of quality control of some major haematological techniques are described. These methods have been applied in haematology laboratories serving a population of 2 million using existing facilities for preparation and transport of the necessary materials.


Comparison of uridine uptake at 24 hours with thymidine uptake at 72 hours in phytohaemagglutinin-stimulated cultures of pregnant and other subjects. As a possible more rapid test of lymphocyte reactivity to phytohaemagglutinin (PHA) than the standard estimation of thymidine uptake after 72 hours (T72), uridine uptake after 24 hours (U24) was studied in a total of 96 individuals. No reliable correlation between the two estimations was found in 29 outpatients showing a wide range of reactivity to PHA nor in 30 healthy control subjects nor in 16 pregnant subjects. Conflicting reports have appeared in the literature as to whether lymphocyte reactivity to PHA is normal, depressed or enhanced in pregnancy. Our group of pregnant subjects showed a significant depression of both U24 (P less than 0-01) and T72 (P less than 0-02) results as compared to normal female controls. Cultures of semipurified lymphocytes prepared by gradient centrifugation on a further 21 normal control subjects showed no better correlation between U24 and T72 results than the above unpurified-leucocyte cultures.


Infection with minute-colony-forming beta-haemolytic streptococci. One hundred and thirty-one strains of minute-colony-forming beta-haemolytic streptococci were isolated during the course of routine investigations in clinical bacteriology. Each strain was examined for the presence of polysaccharide antigens of Lancefield's groups A, C, G, and F and characterized in detail as to biochemical and cultural features. On the results of these tests it is concluded that the strains should be placed in the species Streptococcus milleri. The clinical details relevant to the various strains are summarized according to the site of isolation, and their pathological significance is discussed.


Assay of gentamicin in cerebrospinal fluid. A comparison of standard curves obtained from a conventional plate diffusion assay method revealed significant differences when gentamicin standards were made up in different media. Standards made up in distilled water resulted in a curve which differed from that of standards made up in pooled human cerebrospinal fluid by a factor of up to 4. When the assay medium was supplemented with 0-5% sodium chloride, the difference between the two standard curves was reduced to a factor of about 1-5. The curve obtained from standards made up in 150 mM sodium chloride/4-5 mM calcium chloride correlated well with that from standards made up in cerebrospinal fluid. There was no evidence of gentamicin being bound to protein in the cerebrospinal fluid.


Regeneration of retinal axons into the goldfish optic tectum. The growth of regenerating retinal axons into the central portion of the optic tectum of adult goldfish was examined with the light and electron microscopes. Optic tracts were cut and, two days to five months later, the animals were perfused and the tecta prepared for microscopy. Regenerating axons first reached central regions of the tectum seven to ten days postoperatively. Regenerating axons appear in very large numbers and travel in fascicles in the stratum opticum (SO) and in the adjacent neuropil, the stratum fibrosum et griseum superficiale (SFGS). In the SO, the fascicles are bordered by glial cells and degenerating debris. Within the SFGS, however, the fascicles do not seem to be similarly associated with glial cells and degenerating debris. The youngest regenerating axons are very slender processes, containing microtubules but few or no neurofilaments or dense granular material. By 10 to 14 days postoperatively, neurofilaments can be seen and, in addition, large numbers of vesicles with dense cores appear. The vesicles with dense cores increase in numbers until about 28 days postoperatively and then become quite rare. That vesicles with dense cores were seen in regenerating axons in both SO and SFGS during the period of growth into the tectum but were not seen in axon terminals at any time, suggests that they may be concerned with axon elongation. During the period one month to five months postoperatively, the regenerating axons gradually increase in diameter but do not reach preoperative sizes, suggesting that the regenerative changes may still be occurring. Remyelination is delayed and proceeds slowly. Many axons remain unmyelinated for as long as five months postoperatively.


Reconstruction of neurons of dorsal horn proper using Golgi-stained serial sections. Three neurons located in the dorsal horn (Lamina III) have been reconstructed using Golgi-stained serial sections. These cells including dendritic and axonal branchings appear to remain within the dorsal horn and to belong to small-sized local interneurons of the dorsal horn proper. The measurements have been made with various criteria: the medio-lateral, dorso-ventral and rostro-caudal extents of the dendritic tree as well as the axonal branchings, total dendritic and axonal length, number of axonal endings and distance from the starting point of the axon at the dendrite to the point where the dendrite joins the soma (S-A distance).


Trigeminal projections in snakes possessing infrared sensitivity. The first order of projections of the trigeminal nerve were studied in four species of snakes, three of which are infrared sensitive, utilizing silver degeneration and cobalt iontophoresis techniques. The trigeminal nerve projected ipsilaterally to a main sensory nucleus, descending spinal nucleus, ventral trigeminal field and solitary nucleus with a contralateral projection to the base of the descending spinal nucleus in all four species. A major additional projection to the lateral nucleus of the trigeminal was present in all three infra-red sensitive species but absent in the other. Iontophoresis of cobalt chloride into a trigeminal branch composed entirely of infrared sensitive fibers and into a trigeminal branch containing no infrared fibers indicated that the lateral nucleus of the trigeminal nerve was the sole first target of the infrared system.


Synapse formation in the mouse olfactory bulb. I. Quantitative studies. A quantitative study of synapse formation in the mouse olfactory bulb has been carried out using serial sections. Volumetric synaptic density as well as absolute number of synapses per olfactory bulb for eight distinct synaptic types have been determined at 15 different ages, from the beginning of synapse formation at embryonic day 14 (E14) to postnatal day 44 (P44). Synapses are first found in appreciable numbers at E15 when both axo-dendritic and a few dendro-dendritic synapses occur in the presumptive glomerular layer. Initial synapse formation correlates closely with the reorientation of mitral cells from a primitive tangenital to a definitive radial direction. Synapse formation by mitral cell dendrites occurs after mitral cell axons have grown into the future olfactory cortical areas, either simultaneous with or before synapse formation by these axons. Virtually all synaptic types detected in adults have been found on the day of birth, consistent with the idea that olfaction is an important sensory modality for newborn mice. Volumeric density of a given synaptic type generally increases 50--100 times during development while the absolute number increases about 1,000 times. Synapses in glomeruli develop more precociously than those in the time of origin and differentiation of the principal postsynaptic elements of these two divisions (mitral cells and internal granule cells). Correlation of the time of synapse formation of various synaptic types with their putative excitary or inhibitory role determined in adult studies suggests that excitatory synapses generally form somewhat earlier, although throughout nearly all of synaptic development, both excitatory and inhibitory synapses are present. Reciprocal dendro-dendritic synapses in the external plexiform layer appear to have a special mode of formation. It is suggested that a granule-to-mitral dendro-dendritic synapse only forms next to an already existing mitral-to-granule synapse on the same gemmule.


Synapse formation in the mouse olfactory bulb. II. Morphogenesis. Serial thin sections of the mouse olfactory bulb from the fourteenth day of gestation (E14) to postnatal to 44 (P44) have been examined in order to study morphogenesis of individual synaptic junctions. At the initiation of synapse formation structures are found that resemble postsynaptic densities but are facing extracellular space or unmodified processes. Transition forms between these isolated postsynaptic densities and undoubted synapses have been found. These observations as well as quantitative studies support the hypothesis that isolated postsynaptic densities can form independently and be converted to synapses when a presynaptic specialization develops opposite them. Detailed studies of olfactory axodendritic synaptogenesis throughout the entire developmental period suggests strongly that these asymmetrical synapses pass through an immature symmetrical phase: (1) symmetrical olfactory axodendritic synapses are found in significantly higher concentration on axonal and dendritic growth cones than on more common processes; (2) the number of symmetrical synapses is correlated with the rate of formation of new synapses determined previously. The time for a recognizable symmetrical synapse to be transformed into a recognizable asymmetrical one has been calculated to be 9--10 hours. A scheme of synapse formation in the CNS has been proposed in which a post-synaptic structure forms independently followed by aggregation of pre-existing presynaptic components into a presynaptic specialization. Different morphogenetic sequences of synapse formation from region to region are attributed simply to different relative rates in the development of the postsynaptic density and the presynaptic specialization.


Properties of ganglion cells in the visual streak of the cat's retina. The properties of ganglion cells in the visual streak of the cat's retina have been investigated. Evidence is presented that the streak is formed principally, but not entirely, by a concentration of small-bodied ganglion cells with the receptive field properties and slow-conducting axons typical of W-cells.


Differential effects of unilateral and bilateral caudate lesions on side preferences and timing behavior in rats. Rats were trained to bar press on a differential-reinformcement-of-low-rate 16-sec (DRL 16) schedule for water reinforcement. On alternate days, rats were tested in the presence or absence of a light that signaled the availability of reinforcement. Rats were allowed to bar press on either of two levers (left and right). All rats showed consistent side preferences. For the non-signaled condition but not for the signaled condition, normal baseline rates were related to the strength of side preferences; lower rates and better timing performance were significantly correlated with greater preferences. Unilateral lesions in the caudate nucleus ipsilateral to side preferences facilitated timing performance during nonsignaled test sessions and increased side preferences during both nonsignaled and signaled sessions. Unilateral caudate lesions contralateral to side preferences impaired timing performance during nonsignaled test sessions and decreased side preferences during all sessions. Bilateral caudate lesions transiently depressed response rates without significantly affecting timing performance or side preferences. It is suggested that side preferences are intimately involved in the control of behavior by internal stimuli and that an inherent asymmetry in nigrostriatal function underlies side preferences; the effect of a unilateral striatal lesion will depend upon whether the lesion is placed in the more or less active striatum.


Evidence against the response-shift account of hyperstriatal function in the pigeon (Columba livia). Pigeons with hyperstriatal lesions and unoperated controls were given minimal or extended side-key pretraining prior to acquisition of a position discrimination. Operated birds were impaired following extended, but not minimal, pretraining. The birds then acquired a simultaneous color discrimination with posiversals of the color discrimination, operated birds were impaired, and this was primarily due to an exaggeration of perseverative responding to the former positive stimulus. Analysis of choice latencies found no tendency towards an exaggerated "Mahut effect" in hyperstriatals and indicated that operated subjects used the same solution strategies as normals. These findings directly contradict the response-shift account of hyperstriatal function and indicate a return to the response-inhibition hypothesis.


Polarized light discrimination by pigeons and an electroretinographic correlate. Pigeons placed in a multiple-key Skinner-box could be trained to choose reliably keys that were aligned in a specific way with the polarization axis of an overhead, randomly rotating light source. On the basis of these results and those of additional control experiments, it is concluded that pigeons can discriminate the axis orientation of linearly polarized light and, furthermore, that they can orient themselves spatially by this cue. Electrophysiological recording experiments showed that the shape of the b-wave of the pigeons' electroretinogram is affected by the axis orientation of linearly polarized flash stimuli. This phenomenon seems to be due to the presence of retinal polarization analyzers that may be tied to color vision mechanisms.


Experiential and hormonal conditions affect squab-egg choice in ring doves (Streptopelia risoria). Noncycling, progesterone-injected, experienced male ring doves prefer eggs to squabs in a simultaneous squab-egg choice test, while experienced male doves injected with both progesterone and prolactin prefer squabs to eggs. When exogenous prolactin is administered to either naive or experienced male ring doves during the early phase of a normal incubation cycle, squab choice is significantly increased. Squab choice is also significantly increased in incubating doves by 24 hr of exposure to a squab in the home nest. This effect is greater in naive than in experienced doves. Squabs introduced during late incubation have more of a positive effect on squab choice than when introduced during early incubation. It is concluded that intracyclic experience organizes successive behavioral changes within a reproductive cycle and that naive doves are more affected by some changes in intracyclic events than are experienced doves.


Facilitation of receptivity in estrogen-primed rats during successive mating tests with progestins and methysergide. The role of hormonal and experiential variables in mediating the gradual increase of receptivity occurring during weekly tests was evaluated in adult ovariectomized females. Hormone treatment consisted of estradiol benzoate (EB) injection followed by progesterone (P), 20alpha-hydroxyprogesterone (20alpha-OHP), methysergide maleate (Me), or oil during weekly mating tests. The experiential conditions were vaginal stimulation, mounts only, or no interaction with males. There was a gradual increase in receptivity in all groups even en the one receiving oil. Progressive facilitation occurred even when no interaction with the male was permitted. Interchanging the synergists on the sixth and seventh tests was not detrimental to the display of receptivity attained with synergists given previously. Thus, we concluded that successive injections of EB rather than synergists or experience mediate this increase in receptivity.


Carotene and immunoglobulin concentrations in the colostrum and milk of pasture-fed cows. The carotene and immunoglobulin concentrations in colostra and milks of 6 Jersey, 4 Friesian and 6 Jersey x Friesian cows were determined during the first 21 d of lactation. Carotene concentrations of between 50 and 300ug/g milk fat were found at first milking and these declined to normal concentrations, in the range 9-21ug/g milk fat, by the eighth to tenth day of lactation. Immunoglobulin concentrations at first milking were in the range 4-40g/l milk and decreased to normal concentrations, in the range 0.3-0.5g/l, by the fifth to seventh day of lactation. For both substances the data from each cow's milk fitted an exponential decay model. The fractional rates of decrease in concentration of carotene were 0.19-0.57/d and of immunoglobulin were 0.40-0.73/d. Breed-group differences were observed in both carotene and immunoglobulin concentrations in milks after the fourteenth day of lactation. In Jersey milks, the average carotene and immunoglobulin concentrations were respectively 18.5 ug/g milk fat and 0.32g/l of milk, while in Friesian milks the concentrations were respectively 11.4 ug/g milk fat and 0.46 g/l milk. There was also a difference between breed groups in the daily rates of decrease of the immunoglobulin concentrations. The average rate of decrease for the Friesians was about 1.5 times the rate for the Jerseys.


Autoxidation in milk rich in linoleic acid. II. Modification of the initiation system and control of oxidation. Factors contributing to the initiation of lipid oxidation in cow's and mare's milk containing high levels of polyunsaturated fatty acids were studied. Addition of H2O2 just after milking, in slight excess of the stoichiometric amounts required to destroy ascorbic acid, delayed the development of oxidized flavours in cow's milk high in linoleic acid. Hydrogen peroxide treatment followed by the addition of alpha-or gamma-tocopherols prevented lipid oxidation in cow's milk even when 0.1 mg Cu/l milk was added. When used separately in the presence of Cu these treatments were ineffective as was butylated hydroxyanisole treatment. The lipid and ascorbic acid in mare's milk were remarkably stable to oxidation. Addition of 0.05 or 0.1 mg Cu/l, ethylenediamine tetraacetic acid, neocuproine, or H2O2 had very little effect on the loss of ascorbic acid and lipid oxidation in mare's milk.


Enzymic methods for estimation of the somatic cell count in bovine milk. 1. Development of assay techniques and a study of their usefulness in evaluating the somatic cell content of milk. Assay procedures were developed for a number of enzymes in milk which apparently originate from leucocytes. The enzymes studied were acid phosphatase, N-acetyl-beta-D-glucosaminidase, beta-glucuronidase, arylsulphatase, alpha-mannosidase, and catalase. Quarter-milk samples were analysed for enzyme activity and results compared with the electronic cell count and the Wisconsin Mastitis Test. All enzymes measured except acid phosphatase and alpha-mannosidase showed good correlation with the electronic cell count. Of the other 4 enzymes tested, beta-glucuronidase and arylsulphatase were unsuitable as diagnostic aids owing to the lengthy incubation periods required in their assay procedures. The assay of catalase, which involved the measurement of the initial rate of release of O2 using an O2 analyser apparatus, was rapid, sensitive and reasonably reliable, if fresh milk samples were used. The assay procedure for N-acetyl-beta-D-glucosaminidase was considered to be the most reliable, simple and rapid enzymic method for estimating the number of somatic cells in milk.


Autolysis of Streptococcus cremoris.

Autolysis of Streptococcus cremoris. The autolysin of Streptococcus cremoris had the specificity of an endo-N-acetylmuramidase as it hydrolysed the linkage between N-acetylmuramic acid and N-acetylglucosamine. The enzyme had no amidase or endopeptidase action. It reached highest activity in the exponential phase of growth and in the electron microscope seemed to fragment the coccal wall at the equatorial ring.


Factors that influence milk cholesterol and lipid phosphorus: content and distribution. Average cholesterol content of 356 raw milk samples was 152.2 mug/ml and upon centrifugation (3000 X g for 8 min), 16.9% was distributed in the skim milk phase. Lipid phosphorus averaged 19.0 mug/ml and was partitioned 50:50 between cream and skim milk phases. Weight ratios of cholesterol to lipid phosphorus for milk and skim milk were 8.30:1 and 2.94:1. When variation due to milk yield, fat percent, and somatic cell numbers (deoxyribonucleic acid percent reflectance) was accounted for by least squares, cholesterol content and distribution did not differ among breeds (Holstein, Jersey, and Guernsey). Breed differences in lipid phosphorus content of whole milk could not be detected. However, Holsteins had a significantly lower content of lipid phosphorus and a higher weight ratio for skim milk. Milk yield, fat content, and somatic cells affected responses of cholesterol and lipid phosphorus. This supports a multiple origin concept for membrane material in skim milk.


Adenosine triphosphate in milk.

Adenosine triphosphate in milk. Freshly secreted goat's milk contains a number of viable metabolic pathways including those for the synthesis of triglycerides and phospholipids. Toward understanding this matter, amounts of the fundamentally important energy substrate, adenosine triphosphate, in goat's milk were evaluated. Milk left in the goat udder overnight had less adenosine triphosphate (12.4 muM) than fresh secreted milk (37.6 muM). In similar experiments the skim milk derived from whole accumulating in the udder overnight was lower in adenosine triphosphate (14.2 muM) than skim milk from freshly secreted milk (26.0 muM). To determine changes in quantities of adenosine triphosphate after milking, milks were divided into two parts, one containing only milk and the other milk plus 2,4-dinitrophenol and sodium arsenate, inhibitors of oxidative and substrate level phosphorylation. Adenosine triphosphate in milk decreased during 4-h in vitro incubations, and the rate of decline was markedly greater in the presence of the inhibitors. Thus, freshly secreted goat's milk contains significant amounts of adenosine triphosphate, and more can be synthesized therein after removal from the udder. In limited samples human and bovine milks contained much lower concentrations of the compound than those in goat's milk.


Relative activation of milk lipoprotein lipase by serum of cows fed varying amounts of fat. A routine laboratory assay to evaluate relative concentrations of lipoprotein lipase activator (apo C-II) in cow serum was developed. The assay was linear for at least 120 min after an initial, unexplained, lag ime of 13 to 15 min. Half-maximal activation was in the range of 1 to 2% serum in the assay. Inhibition of activation was indicated at high amounts (10%) of serum. Activation from plasma was half that from serum, presumably caused by an increase in substrate Km in the presence of heparin. Use of glyceryl tri[9,10-3H] oleate yielded excessively high blanks; [2-3H] glyceryl triolein is suggested for routine assay. Relative amounts of activator were not different between dry and lactating cows fed "conventional" diets. Activator concentration increased linearly with increasing dietary fat and was related to concentration of total lipid in plasma. The assay may provide a useful adjunct in studies on lipoprotein metabolism.


Mechanisms of secretion: effects of colchicine and vincristine on composition and flow of milk in the goat. Colchicine, the plant alkaloid, produced a dramatic decrease in milk flow when infused into the udder of the goat. The compound (1 to 5 mg) dissolved in 5 ml of water was inserted into one side of the under via the teat canal. Such treatments consistently caused a depression in milk yield from the infused side with maximum at 36 h and substantial reversal by 72 to 96 h. Milks from both the infused and uninfused sides of the udder were essentially normal in composition (fat, protein, and lactose). However, globulins and riboflavin were elevated in milks from the infused side. The plant alkaloid, vincristine, produced effects on milk secretion similar to those of colchicine but at dosages roughly one-tenth the latter. The two substances had no effect on the amount of milk from the uninfused side of the udder. Experiments employing [carbon-14] colchicine revealed that less than 20% of the infused colchicine is secreted in the milk. Both the secretion of fat globules and the emptying of secretory vesicles by the lactating cell are inhibited by colchicine indicating that a portion of the cell population is turned off from secretion. Plant substances such as colchicine and vincristine may at times limit yields of milk, especially in grazing ruminants.


Distribution and clearance of polybrominated biphenyls in cows and calves. The distribution and clearance of polybrominated biphenyls were determined in two cows and a calf fed polybrominated biphenyls by boluses, by placental transport to a calf from a contaminated dam, and to another calf via milk from the contaminated dam. Feces were an important route of excretion of polybrominated biphenyls during exposure and the period when the contaminated feed was cleared from the digestive tract. Approximately 50% of single intraruminal doses of these hydrocarbons were cleared by 168 h. Free polybrominated biphenyls in urine could not be quantitated. However, 24% of carbon-14 from tetrachlorobiphenyl was recovered, suggesting that significant quantities of halogenated biphenyl may be excreted in urine. Milk was also an important excretion route with one cow excreting 23% of the polybrominated biphenyl dose in 168 days. Concentrations of polybrominated biphenyls in the fat of most tissues were similar, with higher concentrations in liver and lower in the nervous system. Gross or histopathologic lesions of tissues collected at necropsy could not be related specifically to polybrominated biphenyl toxicity.


Excretion of levamisole in milk from cows treated with various formulations. The rate of disappearance of levamisole in milk from cows given levamisole hydrochloride drench, levamisole resinate in feed pellets, levamisole hydrochloride boluses, or levamisole phosphate injectable was determined. Each formulation was given as a single treatment to each of five cows at a rate equivalent to 8 mg of levamisole hydrochloride/kg of body weight. Levamisole hydrochloride residues in milk averaged .50, .55, .58, and .32 ppm at 12 hr after the administration of levamisole drench, feed, bolus, and injectable formulations. Levamisole hydrochloride residues were below .01 ppm in milk at 48 h after drench treatment and at 60 h after treatment with other three formulations. Toxicity symptoms were not observed in any cows following treatment.


Factors influencing rumen fermentation: effect of hydrogen on formation of propionate. The effect of hydrogen on fermentation of lactate, pyruvate, fumarate, and succinate by resting rumen microorganisms has been investigated. Under an atmosphere of nitrogen, lactate was fermented to yield acetate as the major product (85 to 100 mole %) and propionate (0 to 17 mole %) and butyrate (0 to 3%) as secondary products. Under hydrogen, there was increased formation of both propionate and total volatile fatty acids. The amount of propionate increased 4 to 8 times and total volatile fatty acids 2.5 to 3.2 times. Propionate formation was proportional to the hydrogen concentration and reached a maximum at a partial pressure of hydrogen of .2 N/m2. With [2-carbon-14] lactate, propionate was formed via the dicarboxylic acid pathway under both nitrogen or hydrogen. Hydrogen did not affect significantly the fermentation of pyruvate or succinate. With fumarate under hydrogen, propionate and total volatile fatty acids increased 6.8 and 2 times while acetate was unchanged. The mechanism by which hydrogen exerts these effects is discussed in relation to the role of methanogenesis in the rumen.


Coffee grounds. I. Effects of coffee grounds on ration digestibility and diuresis in cattle, on in vitro rumen fermentation, and on rat growth. Holstein steers were used to compare rations in which coffee grounds replaced grain at rates of 0, 5, 10, or 20%. The coffee grounds analyzed (%) dry matter 91.1, protein 11.8, fat 23.1, fiber 42.5, ash .7, and caffeine .13. Digestibility coefficients for dry matter, crude protein, and energy decreased, and ether extract increased progressively as concentrations of coffee grounds in the ration were increased. There was a significant decrease in nitrogen retention and utilization when the rations contained 10 or 20% coffee grounds. Coffee grounds depressed feed intake, increased urinary output, and increased water intake (based on dry matter intake). Coffee grounds caused diuresis and renal, urethral, and bladder irritation. Adding coffee grounds up to 35% of the substrate did not depress rumen microbial fermentation, as measured by in vitro gas production. Weight gain of rats fed rations containing 22.5% untreated coffee grounds was reduced significantly. Water extraction removed some undersirable factors in coffee grounds for rats, and ether extraction removed most of them. Incremental additions of coffee oil (1, 3, or 5%) to the basal diet resulted in incremental decreases in rat weight gain.


Corn grain preserved with ammonium isobutyrate for lactating dairy cattle. Twenty-four lactating cows were fed one of three complete rations containing dry corn, ensiled corn, or corn treated with ammonium isobutyrate in a Latin square arrangement of treatments. Two weeks were used for adjustments to rations and 3 wk for collection of data. There were no differences in average daily yield of milk or fat-corrected milk, but fat percentage of milk from cows fed ensiled corn was lower than that of those given dry corn. Fat test of cows fed treated corn was intermediate and not different from the other groups. Molar proportions of volatile fatty acids and concentrations of rumen ammonia were not different among treatments.


Responses of young calves to low doses of lead. Twenty calves, week-old male Holsteins, 42.8 kg body weight, were assigned to four treatments by oral dose 0, 1.5, 3.0, and 6.0 mg lead carbonate/kg body weight given three times weekly until calf fetal hemoglobin had been converted to 100% adult hemoglobin for 2 consecutive wk. Analyses were for the first 7 wk when data were complete. Variables included lead in blood, body weight changes, erythrocyte delta-aminolevulinic acid dehydrase activity, packed cell volume, hemoglobin, conversion of fetal to adult hemoglobin, and erythrocyte 2,3-diphosphoglyceric acid. Early changes due to lead treatment were inhibition of delta-aminolevulinic acid dehydrase at all doses and increased loss of hemoglobin at 3.0 and 6.0 mg doses. Growth rate was not impaired seriously by lead treatment. The 2,3-diphosphoglyceric acid in erythrocytes reached peak value at 3 to 4 wk of age and then decreased with age, but 2,3-diphosphoglyceric acid of the treated calves was not changed by the low lead dosing. Low lead dosing will induce early metabolic changes in the young calf prior to inhibition of growth.


Characterization of fatty acid synthesis by cow mammary subcellular fractions. Cellular site of fatty acid synthesis was investigated with mammary tissue from lactating cows. Cytosol, mitochondrial, and microsomal fractions were obtained by differential centrifugation and characterized by measurement of marker enzymes. Two incubation media were utilized to quantitate acetate incorporation into fatty acids by the subcellular fractions. The cytosol fraction synthesized fatty acids from 4 to 16-carbons in chain length with the pattern similar to those synthesized in vivo. No significant acetate incorporation into fatty acids was obtained with mitochondria or microsomal incubations. The malonyl-CoA pathway was the predominant pathway of fatty acid synthesis in cow mammary cytosol as evidenced by inhibitory studies with avidin.


Relation between mammary gland development and body weight. Mammary gland indices including deoxyribonucleic  acid, dry fat-free tissue, and wet weight were correlated with body weight in species having a range of 20,000 fold in body weight. Included were mice, hamsters, rats, guinea pigs, rabbits, sheep, and cattle. From limited data accumulated at Missouri, the relation of deoxyribonucleic acid of mammary gland (Y, mg) to bodyweight (X, g) was Y = .53X-79 at the peak of lactation, Y = .29X-82 at the end of pregnancy, and Y = .056X-84 at the beginning of pregnancy. Comparing mammary dry fat-free tissue (mg) to body weight resulted in: Y = 20X-80, Y = 9.7X-85, and Y = 2.6X-91 in the same order while equations for mammary gland wet weight (mg) and body weight were: Y = 135X-82, Y = 123X-79, and Y = 38X-85. The composite value for regression (b) when all data were combined was .80. These mammary indices relate to but are slightly higher than metabolic body weight which is accepted generally as body weight to the three-quarter power.


Measurement of 25-hydroxycholecalciferol in the bovine. Bovine plasma 25-hydroxycholecalciferol was estimated by rapid protein binding assay. Serum-binding proteins in the assay were from rats deficient in vitamin D and from normal rats; no differences existed in standard curves. Nanograms 25-hydroxycholecalciferol in eight cows averaged 45.5 +/- 12.2 ml of plasma. Results from the rapid protein binding assay compared favorably (greater than 10% deviation) with values from a 25-hydroxycholecalciferol assay involving high pressure liquid chromatography.


Prenancy diagnosis in dairy cattle by progesterone concentration in milk. Concentration of progesterone in whole milk was used to diagnose pregnancy in lactating dairy cows. Milk samples were taken 21 to 22 days postbreeding and analyzed for progesterone by radioimmunoassay. Progesterone in milk greater than 11 ng/ml, 8 to 11 ng/ml, and less than 8 ng/ml was used classify animals as pregnant, questionable, and not pregnant. In this classification for 123 cows, 67 were classified pregnant, 7 questionable, and 49 not pregnant. A comparison of progesterone diagnosis with actual calving results showed agreement of 73 and 98% for the cows classified as pregnant and not pregnant. Thirteen of 19 animals, in which there were discrepancies between diagnoses by milk progesterone and calving results, were not detected in estrus within 30 days after breeding. One animal classified not pregnant by milk progesterone was pregnant.


The cross-reactivity of IgE antibodies with pollen allergens. I. Analyses of various species of grass pollens. Atopic patients with histories of grass pollen allergy often are sensitive to a variety of species of grasses. Using a serum pool from patients sensitive to June grass, we analyzed the reactivity of IgE antibodies to seven grasses by the radioallergosorbent test. Extracts were analyzed for their inhibitory activities with solid-phase allergens prepared from all of the grass pollen. Also samples of serum were exhaustively absorved with solid-phase allergens and the supernatants tested to determine the reactivity of the remaining IgE antibodies. Three patterns of reactivity were observed: (1) June, orchard, meadow fescue, and perennial rye grasses displayed similar reactivity in both inhibition and absorption studies; (2) sweet vernal and Bermuda grasses were considerably less reactive with the serum pool, indicating that they lacked antigenic determinants possessed by the other grasses; and (3) timothy grass possessed unique antigenic determinants. Knowledge of these patterns of cross-allergenicity is of importance for diagnosis and treatment of sensitive patients as well as for in vitro standardization of extracts.


The cross-reactivity of IgE antibodies with pollen allergens. II. Analyses of various species of ragweed and other fall weed pollens. Although the antigenic composition of short ragweed pollen has been extensively investigated, very few studies have analyzed the allergenic cross-reactivity among various types of ragweed pollens. Using a serum pool from patients sensitive to short ragweed, we studied the cross-reactivity of IgE antibodies to six ragweeds by the radioallergosorbent test. Extracts were analyzed for their inhibitory activities with solid-phase allergens prepared from all of the ragweed pollens. Also, samples of serum were absorbed with the various solid-phase allergens and the reactivity of the remaining IgE antibodies was determined. Two patterns of reactivity were observed. Short, giant, western, and false ragweeds displayed comparable reactivity in both inhibition and absorption experiments. Slender and southern ragweed were considerably less active, indicating that they lacked allergenic groupings possessed by the other species. These same patterns of cross-reactivity were found using ragweed pollens from four commercial sources. Knowledge of these patterns of cross-allergenicity is of importance for diagnosis and treatment of sensitive patients as well as for in vitro standardization of extracts.


Transfer factor: hypoxanthine is a major component of a fraction with in vivo activity. Transfer factor was prepared from the leukocyte lysates of four donors with known skin test reactivity. After ultrafiltration and double-gel filtration on polyacrylamide gels, fraction IV of the preparation was found to have biologic activity. This fraction contained one major and occasionally one minor ultraviolet-absorbing and zero to one ninhydrin-detectable spots on thin-layer chromatography. The major ultraviolet spot was identified as hypoxanthine. Hypoxanthine was demonstrated to be responsible for the high 260 nm/280 nm ratio of preparations with biologic activity in vivo. It was not determined if hypoxanthine is required for transfer factor activity. In addition, an orcinol-negative preparation also had biologic activity.


Nonorganic adverse reactions to aeroallergen immunotherapy. Ten patients are presented who exhibited adverse reactions to immunotherapy (IT) which mimicked immunologically mediated reactions but were thought to be nonorganic in etiology. The nonorganic nature of the reactions was considered to be established in 6 of these patients and highly likely in the remaining 4. These reactions tended to occur in young patients, particularly women, at relatively low allergen extract doses and were associated with minimal or no objective findings. There was a high incidence of coexisting or contributory psychiatric problems in these patients, particularly involving hysterical or hypochondriacal personality traits. In some patients presenting with nonorganic adverse reactions to immunotherapy, it appears that the immunotherapy may be successfully continued after the patient gains insight into the nature of the reactions. In other patients, however, these reactions may necessitate discontinuing immunotherapy, and in still other patients, these reactions may confirm the need for psychiatric consultations.


Cardiopulmonary effects of long-term bronchodilator administration. Because of reports of drug tolerance occurring with chronic use of adrenergic agents in asthma, we investigated cardiopulmonary responsiveness to ephedrine and to the beta-2 agent, tebutaline, following chronic drug administration for periods up to one year. With chronic drug administration baseline (prior to daily medication) FEV increased 19% in the terbutaline group and 3.5% in the ephedrine group. An additional increase of FEV above baseline of 23% for terbutaline and 12% for ephedrine was noted after daily medication. Terbutaline also had a longer duration of effect; peak response after ephedrine occurred at 2 hr while terbutaline effect was maximal at 3 to 4 hr. There was no evidence for reduced responsiveness to the bronchodilator actions of either drug at any time. Despite prolonged use, both drugs continue to increase heart rate and pulse pressure moderately following ingestion, with a peak effect occurring at 3 hr; however, pulse pressure widened after terbutaline because of a diastolic fall, while the major effect of ephedrine was to increase systolic pressure. Baseline blood pressure, particularly diastolic, declined progressively with continued drug use. No evidence of cardiac, ehpatic, renal, or ophthalmologic toxicity or change in need for other bronchodilator agents was noted during the study with either drug.


Group dynamics--a point of view. People, interaction, and change. Group dynamics is analyzed both as a science and as an art. Three major elements--people, their interaction, and the change emanating from that interaction--are discussed. People come together as a group with basic needs, such as the need to feel important. Ideally, they will feel some cooperative sense of unity; inevitably, they will interact. Passive, verbal, or restless--as the case may be--they will influence one another toward a positive or a negative goal. For a successful, total group experience, good leadership is essential, with planning to insure a climate of discovery, properly budgeted time, and realistic goals, with allowances for limitations. Group participants help each other learn, and spectators become doers who achieve goals. Guidelines, techniques, and recommended reading accompany the article.


Sociologic study of food habits--a review. II. Differentiation, accessibility and solidarity. The process of changing food habits is more complex than would appear to most nutritionists; it involves much more than the collection of information. Change must be studied from a multidisciplinary, chiefly a sociologic, point of view, since the food habits of families within a community are formed in a matrix of human relationships. Three major variables are presented and discussed: (a)differentiation, the capacity to process information; (b)accessibility, the measured distance between a family and an information source; and (c)solidarity, the ability of a family group to react cohesively to proposed change. To effect change in his dietary habits, an individual needs his family's cooperation. The nutritionist will do well to rely on the findings of social scientists if proposed changes in family food habits are to be implemented.


A computer-based dietary counseling system. A computer-based dietary counseling system is described. Designed to interact directly with patients,  the program interviews people about their dietary behavior and plans with them a weight-reducing diet of approximately 1,500 kcal. In a preliminary trial, twenty-five volunteers gave critical commentary en route through the interviews. The results provided insight into the process of dietary interviewing by computer and helped in the preparation of an experimental study (10). It is our hope that a revised and expanded version of the program will be helpful to both patients and nutritionists in the management of a variety of clinically important dietary problems.


Clinical dietitians use computer-generated worksheet. Clinical dietitians at the UMC Medical Center expressed a desire for a computer-generated listing of patients which could be used to record pertinent information obtained during patient visitation. An existing computer-stored census file was used as the data base for a computer program developed to print a dietitan's worksheet, which included the patient's name, location, and birth date. The form was printed on 8 1/2


Aging.

Aging. Aging, a wearing-out process which affects everything inanimate and animate, is accelerated by abuse of decelerated by care. The psychologic reaction of aging persons vary considerably. The concept of growing older is much more satisfactory and pleasant than the concept of being old, since the former is applicable to everyone regardless of age whereas the latter carries a finite significance as deterioration progresses. Chronologic age is much less important than biologic age. The desideratum is not longevity but rather a long, useful and meaningful life. Although heredity is of importance in longevity, it is a factor over which at present we have no control. However, we can influence the aging process according to whether we care for or abuse the body. The principal factors in accelerated aging, in order of importance, are: 1) tobacco use (particularly cigarette smoking), 2) lack of exercise, and 3) obesity. Conversely, abstinence from tobacco, exercise within tolerance, and avoidance of obesity not only decelerate aging but result in a better quality of life.


Postmortem study of a case of Werner's syndrome. The postmortem study of a classic case of Werner's syndrome is presented. The subject was a Japanese man who died at the age of 39. Major findings included general microsplanchnia, extreme atrophy of the testes and skin, calcified aortic atherosclerosis, an increase of basophils in the pituitary, aspiration pneumonia, chronic pyelonephritis and a meningioma in the occipital area of the brain. Histologically, no osteoporosis was evident in the lumbar spine and iliac bone. The findings suggest that in Werner's syndrome the dominant pathologic factor may be found in connective tissue other than bone.


Tachyarrhythmias in old age.

Tachyarrhythmias in old age. The electrocardiograms of 1,171 patients above the age of 65 in a predominantly geriatric institution were reviewed to determine the incidence of tachyarrhythmias. Data on the overall incidence and the individual types of arrhythmias are presented. Atrial fibrillation was the most common arrhythmia observed, followed by atrial flutter and supraventricular tachycardia. Atrial fibrillation often was associated with other evidence of myocardial damage. The significance of sinus bradycardia and grade I A-V block in the pathogenesis of atrial fibrillation and the significance of the tachyarrhythmias are discussed.


Hypochondriasis associated with organic brain syndrome: a new approach to therapy. Symptoms of hypochondriasis in patients with organic brain disease usually disappear during the course of an anticoagulant-psychotherapy regimen for the treatment of dementia.


[Acupunctural analgesia in labor. Preliminary study]. The authors report their preliminary results of the use of acupuncture analgesia in normal delivery. They obtained 22 very good results out of 31 cases of low lumbar pain, especially in posterior positions. The figures are not significant yet, but they are encouraging, as far as uterine contraction pain is concerned. The very good results obtained during caesarean section encourage us to persist with the method.


[Appendicular and ureteral adenomyomas. Problem of induction of the stroma in the endometriosis foci]. The authors discuss the contents and interpretation of the theories of pathogenicity of the condition of endometriosis after having defined it in its different forms and sites. Adenomyosis (internal endometriosis) and less than adenomyomata greater than (enternal endometriosis accompanied by smooth muscle hyperplasia) give rise to special problems of histogensis. The induction of fibro-muscular stroma into the area could be brought about by two different mechanisms. There is no need for ectopic endometrial glands to induce stroma in mulleriam organs. On the other hand non-mulleriam organs under the diaphragm seem to need that the glands are present and that they induce the surrounding stroma.


[Measurement of plasma oxytocinase. Comparison with urinary excretion of estrogens]. Plasma cystinylaminopeptidase (CAP) activity and 24 h urinary excretion of oestrogens were measured simultaneously in 102 pathological pregnancies. The correlation between the two chemical assays is weak (p = 0,13, to 0,47). Plasma CAP levels were significantly (p less than 0,01) lowered in cases of fetal death; but urinary oestrogen assays were within the normal limits (p greater than 0,1) in this group. Each assay suggested an equal number of correct or incorrect prognoses. Their association resulted in 9 correct prognoses in 12 pregnancies with unfavourable outcome, but led to 12 unduly bad prognoses in a group of 40 normal births. The association of the two assays allows a more adequate diagnosis of high-risk pregnancies, but has the disadvantage of offering an unduly bad prognosis in a greater number of normal cases.


[An original and effective technic for trachelorrhaphy. Preliminary note]. Extensive commissural tears in the region of the isthmus accompanied by incompetence of the cervix can be easily and successfully treated by an original procedure carried out through the vagina. The technique uses at the same time the general ideas and advantages of the freshening of the surfaces technique uses at the same time the general ideas and advantages of the freshening of the surfaces technique of Emmet, the repair of the isthmus technique of Lash and of Palmer and Shirodkar's cerclage technique for stitching the isthmus of the uterus.


[Activity of serum leucine aminopeptidase lamp in normal and pathologic pregnancies]. The activity of the enzyme leucine aminopeptidase (LAmP) in serum was examined in 305 pregnant women (174 women with normal pregnancy, and 131 women with disturbed pregnancy). The activity of this enzyme increases during the normal development of pregnancy. In disturbed pregnancies, the LAmP activity is lower as compared to normal pregnancies. A peculiar case: toxemia of pregnancy, where the activity of the enzyme is considerably increased. This fact may be compared with the increase of LAmP activity in cases of liver damage. The LAmP activity test in pregnancy is reliable and can be performed practically in every laboratory, thus deserving its place among the many tests meant to assess the normal function of the foeto-placental unit. This test may also help in the diagnostic of some specific pregnancies such as twin pregnancy, hydatidiform mole and extra-uterine pregnancy.


[Surgical treatment of cancer of the vulva. Our experience apropos of 21 cases]. The authors report the anatomoclinical aspects and the treatment of 21 cases of cancer of vulva at the Danang General Hosptial from 1961 to 1974. The treatment is only surgical : total vulvectomy and bilateral femoral, inguinal and pelvic lymphadenectomies (radical vulvectomy). The 5 year survival is 63,3 p. 100. Stages I and II have a better survival rate. Metastasis in nodes determine a poor prognosis.


[Obstetrical tocography. I. Didactic summary]. The importance and value of manometry are presented with examples of patients in labour. It is important to distinguish between the pressures and the forces working on the fetus, especially as far as the causes of fetal bradycardia are concerned. Graphs of magnetic lag are shown in order to demonstrate that the tension on the fetus and sometimes on the placenta and the cord precedes and lasts longer than the increase in hydrostatic pressure which accompanies a contraction. The paper includes the following subjects: Introduction and general observations. The patient and the monitoring device and the tolerance to external and internal manometry by the patient. The concepts of pressure and force. The distrubution of pressures and forces in obstetrics. The measure of forces by their conversion into pressure in a manometric system. The interpretation of the results of the measure of pressure and force in obstetrics.


[Histologic and immunologic study of the testis after ligation of the vas deferens in dogs]. We wanted to study the effect of bilateral ligature and section of the deferentia of 12 dogs from the histological and immunological aspects. We looked for circulating anti-sperm antibodies and anti-basal membrane of the testes antibodies at the same time as histological study to find out what happened to these lesions after epididymo-deferential anastomosis had been carried out 16 weeks later. The histological lesions (disappearance of exfoliation of the germ cells and of necrobiosis of these cells) disapperared after anastomosis. Anti-basal membrane antibodies were never found. Anti-testicular circulating auto-antibodies were never found. Anti-sperm antibodies appeared between 1 and 5 months after ligature and then disappeared a few months later. Failures to fertilise after epiddidymo-deferential anastomoses therefore do not seem to be due to these two factors.


[Automatic analyses of rapid fluctuations of basal fetal heart rate during delivery. Verification of parameters]. The authors using an electronic calculator have measured 3 parameters, which allowed them to carry out quantitative evaluations of rapid variations in basal fetal cardiac rhythms (fluctuation) of 29 samples of fetal heart rate obtained during labour. The three parameters are: 1. Mean variation by intervals. 2. Values for differences in intervals approaching zero. 3. Zero changes in the derived curve. Each of these parameters was compared with the values of fluctuations which were obtained by visual analysis quantified on the same samples of tracings. The results of these coefficients of correlation show that the chosen parameters enable quantitative values for these fluctuations to be obtained.


[Laparotomies during pregnancy. Apropos of 32 cases]. Among the 5612 pregnancies followed at the 2nd Obstetrical and Gynaecological Clinic of the University Hospital of Athens, from July 1969 to December 1974, laparotomy was undertaken 32 times for conditions not associated with pregnancy, an incidence of 0,58%. The laparotomy was performed because of ovarian cysts, fibroids, acute appendicitis and bowel obstruction. The accurate diagnosis, the fetal loss rate, maternal morbidity and mortality were discussed.


[Intraepithelial carcinoma of the cervix uteri. 1) Cytologic detection in gynecologic practice. Our exerience with 15,000 smears]. The best results in screening for subclinical cancer of the cervix are given by cytological studies. The authors in reviewing their experience in this method of screening studied the result of 15,000 smears which gave a diagnosis of 37 cases of intra-epithelial carcinoma of the cervix, which means 1 case of carcinoma in situ diagnosed in every 400 smears. Although the technique is very simple it has to be carried out according to strict criteria at the time of taking the smear, of fixing it immediately and of staining it. There is a group of patients who are at high risk about the age of forty, when there is a marked influence due to parity. But only a systematic policy will bring about diagnosis of pre-invasive carcinoma in cases where the cervix is clinically healthy. The cytology is usually characteristic, though the diagnosis may be difficult during pregnancy, or when hormone contraception is being used or when there is a trichomonas infection present. This explains why we find false positives in 0.03 per cent of cases in this study and false negatives in 0.03 per cent of cases. Their rarity means that the method is 99.94 per cent reliable. Finally, the cervical smear gives an opportunity for studying the vaginal microbial flora as well as the cyto-hormonal state.


[Development of ultrastructural changes in human cervix mucus during the ovarian cycle. Scanning electron microscope study]. The use of the Scanning Electron Microscope has made it possible through observation to study the human cervical mucus through the various stages of the ovarian cycle, as well as to describe the significant variations of the meshed woof making up the ultrastructure during the ovarian cycle. While the slackening of the woof and the dimension of the meshes are minimal at both the beginning and end of the cycle, they reach a maximum on forteenth day. In the ovulatory period, lateral expansions from the filaments are numerous. On the other hand, median and terminal thicknesses are almost inexistant during the same period : their frequency decreases during the first part of the cycle, then increases during the luteal phase. During both the preceding and following days of ovulation, one can observe numerous twistings at the level of the filaments which probably express the relaxation and then contraction of the latter. The preparatory technique as well as the method of observation used appear reliable enough to allow a comparison of the cervical mucus ultrastructure in varied physiological, pathological and experimental situations.


[Acute pancreatitis and pregnancy].

[Acute pancreatitis and pregnancy]. When a pregnant woman presented with a syndrome suggesting obstruction and fever together with jaundice and oliguria the authors remembered the difficulty of clinical diagnosis and the biology of pancreatitis. They studied the connection of this condition with pregnancy, its pathogenesis, its prognosis and its treatment, as well as the various factors that were favourable (treatment with diuretics, the right ovarian vein syndrome).


[Listerosis and pregnancy without fetal disease]. A case of vaginal listeriosis occurring in the sixth month of pregnancy is reported. It was discovered when the patient suffered from symptoms of appendicitis complicated by jaundice and an acute nephritis. It was investigated by vaginal smears and swabs, and by amniocentesis. Treatment was general and local. The fetus was not attacked, the pregnancy continued, resulting in the delivery and birth of an undamaged infant.


[Attempt at a standardized interpretation of testicular histopathology in male sterility]. The authors present a standard for interpreting the histopathology of testicular biopsies carried out during the framework of investigation of male sterility. The standard is based on a study of the alterations in the seminiferous tubes (T), the peritubular membranes (M) and the interstitial tissue (I). This method of histological assessment has been used to study 35 subjects on whom bilateral bipolar biopsies were carried out (130 specimens). The statistical study showed: a) the absence of any difference between the pieces taken from the two poles in each testis; b) the level of concentration of spermatozoa could not be tied up with any of the three histological parameters. This applied also for hormone levels with the exception of GUT which seem to correlate directly with M; c) the presence of a varicocoele does not reflect in any way the membrane or the interstitial tissue; d) spermograms carried out after the biopsies showed that testicular biopsy does not cause permanent trauma to the testis. The advantages and disadvantages of this quantitative method are discussed.


[Bismuth encephalopathy in pregnant women. Apropos of a case]. A case of bismuth encephalopathy in a pregnant woman is reported. The neurological picture, characterized especially by myoclonic attacks, is no different from that found in the non-pregnant state. The principal observations are on three points: - the need to think of a toxic origin of convulsions in pregnancy, - the onset of threatened premature labour during repeated convulsive crises, - the passage of bismuth across the placenta : this has been proved by the levels found in the amniotic fluid (55 mcg per 1,000) and in the cord blood (320 mcg per 1,000). The child, who was normal at birth, developed a transient hypotonus which seemed attributable more to the treatment of the mother with Diazepam and pheno-barbitone than to her having taken bismuth during the pregnancy.


[Intra-epithelial carcinoma of the cervix uteri. Our experience with treatment, the role of conization]. The authors re-emphasize that the sure diagnosis of carcinoma of the cervix depends on histology; having considered a series of 15,000 smears in an article on cytological screening for carcinoma of the cervix. They show that the main prop of this histological examination should definitely be conisation. They furthermore prepare an inventory of the different possible methods of treatment of intra-epithelial carcinoma, stating for each method the advantages and disadvantages of the method. Their attitude to treatment is conservative, and they believe that conisation in every case is sufficient when complete removal of the in situ lesion is carried out whatever the age of the patient is. They state the limits of this method and define clearly the contra-indications for such a scheme of treatment, which can only be carried out routinely with the absolutely necessary cooperation of a cytology laboratory and faultless histology.


[Simultaneous study of the placental, myometrial and cervical circulations (indium 113 and anemometric thermometry). 2. Effect of xanthinol nicotinate]. The authors have studied the action of nicotinate of xantinol on the placental, myometrial and cervical circulations using an isotope technique (Indium 113) and anemometric thermometry. They show that this product in every case increases the flow through the cervix and has little action on the flow through the placenta, except that in rare cases it lessens it. The action on the myometrial circulation varies from woman to woman. There is a significant negative statistical correlation between variation in the circulation through the cervix and the placenta.


[Contractile force, work of the uterus, power developed and resistance of the cervix uteri during labor. Measurements in Poissy units]. Apart from records made of uterine contractions in labour and the progress in dilatation of the cervix, the energy exerted by the uterus to open the cervix can be calculated. The power that is developed and the resistance of the factors that combine to inhibit dilatation of the cervix can also be calculated. Examples are given of promiparous women with a dilatation of 5 cm.


[Electronic surveillance during delivery. A method of reading the tracings]. A method for reading the foetal heart rate tracings and a guide of management advise in each case have been established from a review of the literature and the study of 500 records. The tracings are schematically divided into three categories according to the presumed risk of foetal distress: normal or "tolerable" tracings, alarm symptoms and danger symptoms. For each categorie, and according to the duration of the variations, a type of management is proposed. Other diagnostic means, such as capillary blood pH measurement are desirable to improve the foetal state diagnostic and make the treatment more precise.


[Obstetrical tocography. II. Review of its methodology and a new concept]. The methods employed for measuring pressure have been analysed from the historical and practical points of view. The systems at present in use are criticised and a modification based on catheters with inflatable balloons is described. By this method precise manometry is obtained using a strong material. The patient can unplug the monitoring system without it having to be recalibrated later. Furthermore this system avoids errors which come from movements of the catheter, changes of temperature and accidental increases in pressures. Equally it will stand humidity and sterilisation by heat.


[Uncommon form of vesico-uterine fistula]. A vesico-uterine fistula has been seen after a caesarean section. Unusually, the discharge ran from the bladder to the uterus. The problems of the aetiology, the diagnosis and the treatment are discussed.


[Loco-regional analgesia by electronic stimulation during labor]. This is a preliminary report on an original method of local regional electronic analgesia. From it the first results can be deduced. The threshold for pain which was appreciated at 25 mmHg without electronic stimulation was raised to 48 mm Hg under electronic stimulation. Fetal ill-effects are nil.


[Measurements by ultrasonics of the gestation sac in threatened abortion]. The embryonic sac has been measured and its dimensions compared with normal measurements in cases where symptoms suggest threatened abortion. This has been done with the object of trying to complete visual exploration of the uterine contents in such cases. The distribution of the diameters that have been measured in 148 pathological cases show that the number of those below the lower limit of normal is significantly higher when pregnancy will result in abortion or in premature labour.


[Benign mesothelioma of the genital area]. A case of benign mesothelioma of the genital tract which required two operations to cure is reported. The patient is in a satisfactory condition ten years after the second operation. A bibliography is given.


[Detection of phthiriasis by colposcopy]. The colposcope need not be used solely to examine the mucosa of the cervix and vagina. It can help in the diagnosis of the etiology of genito-pubic phthiriasis by the finding of louse eggs firmly fixed to the hairs, whereas usually only the low magnification microscope shows them up.


[Tetanus and pregnancy. Labor with assisted respiration]. The authors report a rare case in which tetanus occurred with a pregnancy near term. In this particular case of pregnancy with risk for the fetus and mother associated with one another, curative treatment with monitoring of the state of the fetus and assisted respiration for the mother resulted in the birth of a live child who could be brought up normally and a cure for the mother without having to resort to caesarean section.


[Macroscopic examination of the fresh placenta. Statistical analysis of 1,200 cases. Comparison with maternal and neonatal pathology]. We have examined 1,200 placentas in a fresh state and have compared the results of these examinations with maternal pathology on the one hand and the neo-natal pathology on the other hand. It turns out that most abnormalities of pregnancy are associated in a significant way with the pathological findings in the placenta, and that the good or pathological health of the newborn is significantly associated with the normal of pathological character of the placenta. The principal weakness in this method of examination is the absence of information about infection. This is why it seems important to us to carry out smears from the placenta before examining it macroscopically.


[Development of the breasts of the fetus. Effects of the administration of hormonal preparations during pregnancy]. The mammary glands of ten still-birth premature fetuses were studied histologically. In seven cases a combination of oestrogen-progesterone preparations were administered to the mother in early pregnancy for a duration of at least 3 months. In three cases no hormones were administered. According to our observations and the experimental work of other investigators, we may conclude that oestrogenic hormones inhibit the development of the mammary gland.


[Indications of choice for extra-amniotic perfusion of physiologic serum]. After a preliminary report on 20 cases, we have used extra-amniotic perfusion of isotonic saline, in association or not with syntocinon, for performing:--56 2nd trimester therapeutic abortions,--16 labor inductions in interrupted 2nd and 3rd trimester pregnancies, with macerated fetus (missed abortion and missed labor). This method, relatively simple, permits the discharge of the conceptus within a reasonable time. Our experience allowed us to draw the indications of choice in the use of this method, which are the following: 1. When the amniotic puncture may be difficult (at the beginning of the 4th month or if the age of pregnancy is uncertain). 2. When there is an increased risk of hemorrhage with coagulation disorder macerated fetus or some systemic diseases). 3. When there are counter-indications for the use of hypertonic saline solution or prostaglandins (some renal, cardiac or respiratory diseases). 4. When one needs a fetus in a relatively good state for embryologic, histologic or genetic studies, which are important in case of abortion for rubella or chromosomic anomaly. In view of the innocuousness of this method, its use for labor induction in evolutive pregnancies is suggested.


[Transverse laparotomy by supre-pubic detachment of the recti muscles in gynecologic surgery. Apropos of 266 cases]. The authors have studied 266 case histories where supra-pubic detachment of rectus muscles was used according to Cherny's method. This allowed aseptic gynaecological surgery to be carried out in all its forms by a true transverse incision. The advantages are great : it is aesthetic and the incision can be enlarged if necessary indefinitely. This means that surgery can be carried out easily and explains the great rarity of intra-abdominal complications. On the other hand two relatively rare complications do occur with this incision : peritoneal haematomata and lateral herniations. Details have been given of the methods necessary to avoid these complications.


Sequential protein analysis from single identified neurons of Aplysia californica. A microelectrophoretic technique involving polyacrylamide gradient gels and isoelectric focusing. Electrophoresis in polyacrylamide gradient gels and isoelectric focusing in polyacrylamide gels of capillary size are powerful tools for the analysis of molecular weight and charge properties of small protein samples. This is demonstrated using identified neurons from the abdominal ganglion of the sea hare Aplysia californica. Certain cell-specific peptides, which are considered to be neurosecretory, have been shown to be water soluble when ethylene glycol was employed as a mobilizing agent. Although the mode of action of ethylene glycol is not yet understood, this method may be of value for various extraction procedures. The application of a new staining method that is preferential for separations of sodium dodecyl sulfate-proteins yields information about the charge of water-insoluble proteins which has so far been inaccessible. Preliminary results gained by a small, two-dimensional mapping procedure as well as optical density separation patterns of two different nuclear protein fractionation from a single isolated nucleus outline further possibilties of the microgel techniques.


Ultrastructural localization of catalase and L-alpha-hydroxy acid oxidase in microperoxisomes of Hydra. The ultrastructural localization of catalase and L-alpha-hydroxy acid oxidase (LalphaHAO) was studied in two species of Hydra. Diaminobenzidine reaction product of catalase activity was present in small round or elongated bodies resembling microperoxisomes in the epitheliomuscular, digestive and gland cells. They were closely related to the endoplasmic reticulum, and were often found in proximity to deposits of lipid and glycogen. Reaction product of LalphaHAO activity was also associated with the microperoxisomes. With rapidly oxidized substrates, such as L-lactic acid, reaction product diffused into the cytoplasm around the microperoxisomes. With slowly oxidized substrates, such as DL-alpha-hydroxyisovaleric acid, reaction product was restricted to the matrix of the microperoxisomes. No reaction product was present in the microperoxisomes in the absence of substrate or with D-lactic acid. The rate of substrate oxidation measured biochemically roughly paralleled the amount of cytochemical reaction product deposited with different substrates. Microperoxisome-like bodies reactive for LalphaHAO were also found in the epidermal cnidoblasts; however, catalase could not be demonstrated in them. This study provides the first cytochemical evidence for the presence of an H2O2-producing oxidase in microperoxisomes.


Lymphocytic choriomeningitis virus-induced immunosuppression: a virus-induced macrophage defect. Primary immunizing infections with LCM virus result in a transient depression of the in vitro proliferative responses of splenic lymphocytes to mitogens specifically reactive with T cells or B cells. This depression of lymphocyte function is the result of a virus-induced defect in an adherent, phagocytic cell population required for in vitro lymphocyte activation. Depressed responses persist for about 1 week after virus clearance and can be corrected by the addition of normal PEM or 2-ME to infected spleen cell cultures. Although the precise nature of this defect remains unclear, it is postulated that it is due to a productive infection of macrophages and their precursors that renders them dysfunctional. Secondary LCM virus infections do not result in depressed in vitro responses to mitogens, presumably because of rapid virus clearance and limited numbers of infected cells. Primary infections of immunologically immature mice, mice rendered functionally athymic, or mice treated with nonspecific immunosuppressive agents result in LCM virus persistence. Shortly after infection, these animals show a similar depression of immunologic reactivity that returns to normal as the virus carrier state becomes established. Despite virus persistence, few PEM from established LCM virus carrier mice contain viral antigens and these cells function normally. Thus, LCM virus-induced immunosuppression appears to reflect a subtle cytopathic effect of LCM virus replication that is not mediated by the virus-specific cell-mediated immune mechanisms responsible for acute LCM virus disease.


Colchicine-sensitive structures and lymphocyte activation. The possible modulatory role of microtubules or closely related colchicine-sensitive structures in the response of human lymphocytes to mitogenic lectins was investigated. Colchicine (0.1 to 10 muM) AND VINBLASTINE (0.1 TO 10 MUM) inhibited early [14C]-aminoisobutyric acid and late [3H]-thymidine uptake in phytohemagglutinin-and concanavalin A-stimulated human lymphocytes but failed to alter 45Ca uptake. Lumicolchicine, an inactive congener of colchicine, was ineffective in all three systems. Both microtubular agents accentuated and prolonged the early cyclic AMP response to lectin. Little or no alteration in cyclic AMP levels was seen with colchicine or vinblastine alone or in combination with PGE (10MUM) or epinephrine (1muM) suggesting that the effect on cyclic AMP metabolism is largely selective for lectin stimulation. Neither microtunular agent altered 125I-concanacalin A binding. Since the inhibition of DNA synthesis was throughout the culture period and early aminoisobutyric acid uptake is affected, it appears that these agents are acting on an early event, or events, in the activation sequence. Although the mechanism of the inhibition is not known, the effect of colchicine and vinblastine in prolonging the cyclic AMP response to lectin may be involved. Alternatively, alterations in microtubules assembly may exert effects on membrane architecture interfering with propagation of the stimulus from the membrane to the cell interior.


Intestinal uptake of macromolecules. V. Comparison of the in vitro uptake by rat small intestine of antigen-antibody complexes prepared in antibody or antigen excess. The in vitro absorption by rat jejunal and ileal gut sacs of soluble antigen-antibody complexes and of antigen alone was compared. Complexes prepared in 2-fold antibody excess were absorbed in significantly smaller quantities than was antigen alone. Complexes prepared in 50-fold antigen excess were absorbed by jejunal gut sacs in quantities equivalent to that antigen alone, whereas the absorption of such complexes by ileal sacs was somewhat decreased compared to that of antigen. There was less radiolabeled antigen tightly bound to the intestinal mucosa of gut sacs exposed to complexes prepared in antigen or antibody excess compared to antigen alone. Complexes prepared in antibody excess appeared to stimulate secretion of mucus and complexes were associated with the mucus fraction. It was suggested that the large size of complexes prepared in antibody excess may result in their trapping in the mucus coat of the gut, thereby preventing contact with the surface of the enterocyte from whence uptake by pinocytosis is initiated. In addition, complexes appear to be shed from the surface with mucus by a mechanism still to be elucidated.


Immunochemical studies of infectious mononucleosis. V. Isolation and characterization of a glycoprotein from goat erythrocyte membranes. A glycoprotein was isolated from goat erythrocyte membranes by extraction with hot 75% ethanol. The glycoprotein was purified by ethanol precipitation, phosphocellulose chromatography gel filtration, ethyl:ether and chloroform:methanol extraction. In aqueous phosphate-buffered saline, pH 7, the glycoprotein was in an aggregated state with a sedimentation coefficient (S(obs)) to 1.5. Electrophoresis of the glycoprotein on polyacrylamide gels containing phosphate-buffered 0.1% SDS gave a single band, staining with both periodic acid Schiff (PAS) and Coomassie Blue (CB). The apparent m.w., calculated from retardation coefficient, was 25,000. Electrophoresis of the glycoprotein on 1% SDS gels buffered with Tris-acetate (pH 7.4) showed a major band of similar (23,500) apparent m.w. plus four other PAS- and CB-staining bands of lower mobility. With 131I-labeled glycoprotein, recovery of bands from gels, sialic acid analysis, heterophile antigen activity, and re-electrophoresis, it was shown that these additional bands were aggregated forms of a single or closely related glycoprotein species. The purified glycoprotein contained 50% carbohydrate with molar ratios of sialic acid:galactose:mannose:galactosamine:glucosamine of 3.1:2.1:0.1:1.6:1. The glycoprotein was highly reactive with the Paul-Bunnell heterophile antibody in the sera of patients with infectious mononucleosis, with Limulus polyphemus lectin and weakly ractive with wheat germ agglutinin. These reactivities were destroyed by neuraminidase treatment or by alkaline sodium borohydride. The native glycoprotein did not react with lectins from Canavalia enisformis, Phaseolus vulgaris, Ricinus communis, or Vicia graminea although it was reactive with the latter two after neuraminidase treatment.


In vitro induction of F1 hybrid anti-parent cell-mediated cytotoxicity. Spleen cells from normal (C57BL/6 X DBA/2)F1 mice were sensitized in vitro for 5 days with irradiated C57BL/6 or DBA/2 parental stimulating cells. Effector cells were generated which specifically lysed 51Cr-labeled targets (leukemia or mitogen-stimulated lymphoid cells) H-2-matched with the parental genotype used for sensitization. The response of F1 spleen cells to the C57BL/6 parent was stronger and more reproducible than that to the DBA/2 parent. The kinetics of generation of effector cells were similar for the F1 anti-parent and an F1 anti-allogeneic response. However, the magnitude of the F1 anti-C57BL/6 cytotoxic response was considerably lower than the F1 response to allogeneic cells. The ratio of responder to stimulator cells in the cultures was more critical for the former than for the latter response. Several lots of fetal bovine serum were found to be adequate for supplementing the medium in the induction of J1 hybrid anti-parent and anti-allogeneic cytotoxic effector cells. Based on these and other studies, it would appear that the F1 hybrid anti-parent cytotoxic response provides an in vitro model of murine hemopoietic graft rejection in vivo. This response may be elicited by a mechanism distinct from T cell-mediated cytotoxicity and involve different subpopulations of spleen cells.


HLA-related control of spontaneous and antibody-dependent cell-mediated cytotoxic activity in humans. Normal human lymphocyte preparations were tested for their ability to lyse both antibody-coated and unsensitized human target cell lines. The capacity to induce these two types of cell-mediated cytotoxicity, antibody-dependent (Ab-CMC) and spontaneous (Sp-CMC), was detected by a 51Cr release assay. The reactivity of lymphocytes from 1. individual donors showed a positive and highly significanlty correlation between Ab-CMC and Sp-CMC, leading to the hypothesis that the same type of effector cell is involved in the two cytotoxic mechanisms. Lymphocytes from male donors were about twice as effective as those from female donors in both systems. Moreover, the effector cells from male donors carrying HLA antigens A3 and B7 displayed a significantly lower reactivity in both Sp-CMC and Ab-CMC when compared with lymphocytes from male donors bearing any other HLA haplotype. The possible significance of the hyporeactivity of lymphocytes from normal subjects with HLA-A3,B7 haplotype in relation to an increased susceptibility to multiple sclerosis (MS) is discussed.


Human transfer factor: effects on lymphocyte transformation. Transfer factor preparations from 57 different donors have been compared for effects on mitogen- and antigen-induced lymphocyte transformation. Nine of the preparations were mitogenic when added to cultured lymphocytes although the magnitude of this activity was relatively low. The majority of the preparations (48/57) did not affect PHA-induced lymphocyte transformation although augmentation (6 of 57) and suppression (3 of 57) was observed with some. In addition we observed that most of the preparations tested suppressed ConA stimulation and augmented the PWM response. When selected preparations were evaluated on antigen-responsive cells, there was a correlation between the magnitude of antigen responsiveness and the magnitude of TF augmentation of antigen-induced lymphocyte transformation (p less than 0.005). Cultures that were not responsive to antigen (KLH-negative or BUdR-treated) could not be stimulated by TF from immune donors and antigen. These data suggest that TF preparations contain either stimulatory or inhibitory components and that TF is not capable of activating naive lymphocytes to undergo transformation in response to antigen.


Antibody-induced killing in vivo of L1210/MTX-R cells quantitated in passively immunized mice with 131I-iododeoxyuridine-labeled cells and whole-body measurement of retained radioactivity. The killing of the LR subline of the DBA/2J leukemia L1210/MTX by passive antibody was followed in vivo with 131I-iododeoxyuridine-labeled cells and whole-body measurement of retained radioactivity. The in vivo killing of LR cells was proportional to the in vitro 2-mercaptoethanol resistant titer, independent of the complement system, and radioresistant. Although a large percentage of the leukemic cells was killed in passively immunized mice, the protective effect of the passive antiserum was dependent on the active immune response of the host.


A new activity of complement component C3: cell-bound C3b potentiates lysis of erythrocytes by C5b,6 and terminal components. EAC4b,3b (sheep erythrocytes carrying rabbit antibody and guinea pig complement component fragments C4b and C3) adsorb human C5b,6 reversibly; the avidity of binding varies inversely with ionic strength. We believe that the receptor of C5b,6 is contributed by the cell-bound C3b because the binding capacity of EAC4b,3b varies with C3b multiplicity and can be blocked with rabbit antibody to guinea pig C3. The fixation of C5b,6 to the erythrocyte-bound C3b serves to concentrate C5b,6 on the cell surface; as a consequence, the hemolytic efficiency of C5b,6 is almost 100 times greater when assayed with EAC4b,3b than with plain erythrocytes. This potentiation represents a hitherto unrecognized function of cell-bound C3b.


Immune response in the hamster. VIII. Ig class differences in susceptibility to tolerance induction. A hemolytic plaque assay was used to quantitate the antibody response of the Syrian hamster after immunization with hen egg albumin (HEA). Whereas HEA in complete Freund's adjuvant (HEA-CF) induced a prolonged heterogeneous (IgM, IgG1 and IgG2) antibody response, the response to soluble HEA in saline (HEA-S) differed in that: 1)both the primary and secondary responses were restricted to the IgG1 class; 2)the IgG1 primary response was cyclical with PFC peaks on days 9 and 16; 3)although an anamnestic secondary response was demonstrated, no further augmentation was noted after tertiary and quaternary boosters; 4)the booster response was transient reaching a peak after 48 hr and declining to low levels within 7 days. Adoptive transfer of lymph node cells to irradiated recipients followed by challenge with HEA-CF revealed: 1)that HEA-S-treated donor cells were primed for an IgG1 response because anamnesis was seen 7 days after challenge, yet on day 21, IgG1 PFC were 20-fold less than that of controls; 2)recipients of HEA-S treated cells showed profound suppression of both IgM and IgG2 PFC on days 14 and 21. These studies indicate that soluble antigen induced in hamsters a state of complete tolerance of IgM and IgG2 classes whereas the anamnestic response of the IgG1 class remained intact.


Influenza A virus interaction with murine lymphocytes. II. Changes in lymphocyte surface properties induced by influenza virus A/Japan 305 (H2N2). This report describes changes in surface properties of rat thoracic duct lymphocytes (TDL) induced by influenza virus A/Japan 305 (H2N2). After incubation with virus at 37 degrees C, sialic acids were released from the membranes of TDL WITH CONCOMItant reduction in their mean electrophoretic mobility. Autoradiographs of TDL which had been incubated with 125I virus at 4 degrees C showed that the particles attached to nearly all the lymphocytes although there was variation in the amount of virus bound per cell. Attachment occurred rapidly with maximum labeling evident after incubation at 4 degrees C for 5 min. Incubation at 37 degrees C for 1 hr resulted in a 10 to 18% reduction in the incidence of labeled TDL suggesting that some virus eluted spontaneously. When 125I-virus-treated TDL were incubated in syngeneic serum, substantial amounts of virus eluted reducing the incidence of labeled cells by 50%. In addition, evidence was obtained by indirect immunofluorescence that syngeneic serum contains antibodies which react with sites on the lymphocyte surface exposed by the viral neuraminidase.


Structure and function of immunoglobulin domains. V. Binding, University of immunoglobulin G and fragments to placental membrane preparations. Fc receptors have been shown to be present in human placental tissue with properties distinct from those on macrophages and lymphocytes. A single class of receptor was observed with an intrinsic affinity 4X 10(6) M-(1) for human IgG1. The order of affinity for IgG subclasses was IgG1 = IGG1 greater than IgG3 greater than IgG4. IgA and IgM were not bound. Fc from IgG1 bound with the same affinity as the whole molecule and to the same number of receptor sites, 2 X 10 (12)/mg placental protein. IgG1 was no longer boung after mild reduction and alkylation whereas the binding of Fc was unaffected by this treatment. Neithe C3 nor C3, the two domains which comprise the Fc region of IgG1, bound to the placental receptor. This implies that this Fc receptor is unlike those found on most cell surfaces and that plasental binding is an exception to the theory that each domain has evoked to perform independent functions.


Evidence for the presence of components of the alternative (properdin) pathway of complement activation in respiratory secretions. Activation of the alternative complement pathway by respiratory secretory IgA was demonstrated by incubating purified, aggregated preparations of serum and secretory IgA with neat human serum. No depletion of the early components (C1-4) was observed, but 63 and 70% of C3-9, respectively, were consumed. The C3-9-consuming capacity of heat-aggregated nasal secretions from an IgA-deficient volunteer was compared with heat-aggregated nasal secretions from a normal volunteer known to have secretory IgA. The deficient secretions consumed C3-9, whereas the IgA deficient secretions did not. Reconstitution of the nasal secretions from the IgA-deficient volunteer with purified secretory IgA produced alternative pathway activation. Factor B of the alternative complement pathway was found to be present in 16 of 18 bronchoalveolar lavage samples (BALF) from normal volunteers. Simultaneous measurement of lavage and serum albumin and Factor B concentrations rendered it unlikely that Factor B was merely a transudative product from serum in half the samples but rather suggested that it may be a component of lower respiratory tract secretions. The presence of an intact alternative complement pathway in BALF was indicated by showing that cobra venom factor and endotoxin cleaved functionally pure human C3 when mixed with BALF, but had no effect on C3 in the absence of BALF.


An indirect radioimmunoassay for thymus leukemia (TL) antigens. An indirect radioimmunassay for thymus leukemia (TL)2 antigens has been developed and its specificity documented. The assay makes use of anti-TL antibodies produced in congenic mice (A-Tla(b)) and radioiodinated purified rabbit anti-mouse IgG. Using this assay, differences can be detected in the amounts of antigen expressed on thymocytes of the three known phenotypes (TL.1,2,3;TL.2;TL-) of inbred mouse strains. Significant differences are also detected in comparison of the thymocytes from homozygous TL.1,2,3 mice (A-Tla(a)) and heterozyhotes from Tla(a) and Tla(b) parents. Optimum conditions for the assay have been established. Its ability to detect antigens on glutaraldehyde-fixed cells and the binding of noncytolytic antibodies on both viable and fixed cells are documented. The assay has also been used to quantitate the changes in TL antigen expression on cells incubated in anti-TL antisera under conditions of antigenic modulation.


The complement profile in babesiosis.

The complement profile in babesiosis. Rats have been infected with Babesia rodhaini, a protozoan agent that induces immune complex disease. Assays for complement have revealed depletion of C2, C3, C4, C5, and whole complement in the course of infection. No evidence of depletion in the alternative (properdin) pathway was found. These findings are consistent with the conclusion that the classical complement pathway is activated during the course of the protozoan infection.


Humoral immunostimulation. VI. Increased calcium uptake by cells treated with antibody and complement. When L cells were treated with anti-L cell antibody in medium depleted of complement, rapid increases in calcium uptake were obtained over a wide range of antiserum concentrations. Concomitant cell growth and viability studies demonstrated that stimulation of cell growth occurred at higher dilutions of antiserum whereas cytotoxicity occurred at lower dilutions. The stimulatory and toxic effects of antibody on cell growth were potentiated by complement as was the enhancement in calcium uptake. Sera deficient in C1R, C2,4D, C4, C3-C9 did not increase the calcium uptake response to antibody whereas augmentation did occur with C6-deficient serum. A specific role for complement was further indicated by the ability of purified complement components to restore the response to complement in complement-deficient sera. C3 with C3-C9 deficient serum, but not C2, C5, and C6 with C3-C9 deficient serum restored augmentation effects. Taken together with the results of previous studies it is apparent that complement augments both calcium and nucleoside uptake and that the effect is primarily via the classical complement pathway through C3. Substrate saturation studies demonstrated that antibody activated the facilitated diffusion of calcium altering the Vmax but not the Km of transport whereas addition of complement altered both the Vmax and Km. These findings suggest that one of the early effects of enhancing antibody upon tumor cell metabolism in vitro is to stimulate uptake of calcium. In view of the suspected role of Ca++ in cell proliferation the increase in cell-associated calcium may be important in the subsequent proliferative response.