Showing papers by "National Institutes of Health published in 1975"
TL;DR: The effect of insulin on CH2O suggests that insulin's effect on sodium excretion is due to enhancement of sodium reabsorption in the diluting segment of the distal nephron, and a reduction in UNaV associated with insulin administration is demonstrated.
Abstract: The effects of insulin on the renal handling of sodium, potassium, calcium, and phosphate were studied in man while maintaining the blood glucose concentration at the fasting level by negative feedback servocontrol of a variable glucose infusion. In studies on six water-loaded normal subjects in a steady state of water diuresis, insulin was administered i.v. to raise the plasma insulin concentration to between 98 and 193 muU/ml and infused at a constant rate of 2 mU/kg body weight per min over a total period of 120 min. The blood glucose concentration was not significantly altered, and there was no change in the filtered load of glucose; glomerular filtration rate (CIN) and renal plasma flow (CPAH) were unchanged. Urinary sodium excretion (UNaV) decreased from 401 plus or minus 46 (SEM) to 213 plus or minus 18 mueq/min during insulin administration, the change becoming significant (P smaller than 0.02) within the 30-60 min collection period. Free water clearance (CH2O) increased from 10.6 plus or minus 0.6 to 13 plus or minus 0.5 ml/min (P smaller than 0.025); osmolar clearance decreased and urine flow was unchanged. There was no change in plasma aldosterone concentration, which was low throughout the studies, and a slight reduction was observed in plasma glucagon concentration. Urinary potassium (UKV) and phosphate (UPV) excretion were also both decreased during insulin administration; UKV decreased from 66 plus or minus 9 to 21 plus or minus 1 mueq/min (P smaller than 0.005), and tupv decreased from 504 plus or minus 93 to 230 plus or minus 43 mug/min (P smaller than 0.01). The change in UKV was associated with a significant reduction in plasma potassium concentration. There was also a statistically significant but small reduction in plasma phosphate concentration which was not considered sufficient alone to account for the large reduction in UPV. Urinary calcium excretion (UCaV) increased from 126 plus or minus 24 to 200 plus or minus 17 mug/min (P smaller than 0.01). These studies demonstrate a reduction in UNaV associated with insulin administration that occurs in the absence of changes in the filtered load of glucose, glomerular filtration rate, renal blood flow, and plasma aldosterone concentration. The effect of insulin on CH2O suggests that insulin's effect on sodium excretion is due to enhancement of sodium reabsorption in the diluting segment of the distal nephron.
1,093 citations
TL;DR: It is postulated that one major subtype of gastric carcinoma ("intestinal type") is the end- result of a series of mutations and cell transformation begun in the first decade of life, which allows the cell to become autonomous and invade other tissues.
971 citations
TL;DR: The first stages in development of a noninvasive method for acquiring information which has a rapid response and the potential ability to distinguish flow in the different microvascular compartments by the differences in flow velocities are reported.
Abstract: THE microcirculation plays a central role in the regulation of the metabolic, haemodynamic and thermal state of the individual. Its physiological state varies over both long and short time periods and reflects the state of health of the individual; in particular it is the ultimatearbiter of the adequacy of tissue perfusion in the presence of vascular disease or injury. For these reasons it is of interest to both the physiologist and the clinician to be able to monitor the state of flow and distribution of flow in the compartments of the microvasculature rapidly, conveniently and with minimal interference with the many local and central reflex controls. At present such measurements depend on direct observation, plethysmography thermal or radioisotope techniques1, which are slow or cumbersome or grossly disturb the normal state of the subject. We report here the first stages in development of a noninvasive method for acquiring such information which has a rapid response and the potential ability to distinguish flow in the different microvascular compartments by the differences in flow velocities.
948 citations
TL;DR: Comparison of age-specific means for the original cohort in 1950 and the offspring in 1972 show apparent reductions in blood pressure, serum cholesterol, and cigarette smoking in the offspring, but in contrast, height in men and women and relative weight in men show significant increases in the children.
837 citations
771 citations
TL;DR: This chapter discusses a study analyzing the three-dimensional structure of immunoglobulins, in which the periodicity of the crystal was used to reduce the background noise and reveal the molecular outline.
Abstract: Publisher Summary This chapter discusses a study analyzing the three-dimensional structure of immunoglobulins. Heavy atom derivatives were obtained. The compounds used were (1) p -chloromercuribenzene sulfonate (PCMBS), (2) mercuric cyanide Hg(CN) 2 , and (3) chloroplatinate ion, (PtCl 6 −− ). X-ray diffraction data were measured for the native crystals and each of the heavy atom derivatives to a Bragg spacing of 6 A. Electron micrographs were prepared of sections of the Dob crystals, cut perpendicular to the short c axis. The crystals were fixed with glutaraldehyde, washed, postfixed in osmium tetroxide, and embedded in Maraglas prior to sectioning. The sections were further stained with uranyl acetate and lead citrate solutions. The method of optical integration was applied in which the periodicity of the crystal was used to reduce the background noise and reveal the molecular outline. An electron density map was calculated with phases obtained from the heavy atom derivatives. The examination of the map showed that one pair of asymmetric units (containing one complete molecule) had density corresponding to three globular regions. One region lay on the twofold axis relating the two halves of the Dob molecule.
733 citations
TL;DR: A rapid succession of two diverse clusters of signs and reactions represents a reversal of the central nervous system function from the extremes of ethanol intoxication to the extremesof ethanol dependence (CNS hyperexcitability) during the withdrawal period.
Abstract: This paper reports findings relative to a simple, rapid and reproducible technique for the induction of physical dependence upon ethanol in the rat. The dependence was induced by intragastric intubation of 20% (w/v) ethanol solutions at 9-15 g/kg in 3-5 fractional doses daily for 4 days, maintaining blood ethanol concentrations above a threshold level sufficient to sustain observable sedation throughout the entire period of intubation. Two phases were distinguished during the withdrawal period: 1. Prodromal detoxication, characterized by a spectrum of signs and responses of diminishing severity, related to the decline in blood ethanol concentrations (mg/dl): death, greater than 640; coma, 780-460; loss of righting reflex, 640-400; ataxia 3-1, 570-250; sedation 340-190; neutrality, 220-130; 2. Ethanol dependence, characterized by a spectrum of withdrawal signs and reactions of progressively increasing severity as blood ehtanol concentration approached 100 mg/dl: hyperactivity, tremors, akinesia, spastic rigidity, and induced and spontaneous convulsions. A rapid sucession of two diverse clusters of signs and reactions represents a reversal of the central nervous system function from the extremes of ethanol intoxication (CNS depression) to the extremes of ethanol dependence (CNS hyperexcitability) during the withdrawal period. Both extremes may terminate in death.
709 citations
TL;DR: Animals and Plants, L. H. Gilbert and P. Raven, Eds.
Abstract: Animals and Plants, L. E. Gilbert and P. H. Raven, Eds. (Univ. ofTexas Press, Austin, 1975), p. 3. 76. J. W. Hanover, Annu Rev. Entomol. 20,75 (1975). 77. R. H. Smith, U.S. For. Serv. Gen. Tech. Rep. PSW-I (1972); A. A. Berryman, BioScience 22, 598 (1972). 78. V. 1. Grimal'skii, L. T. Krushev, V. P. Gorlushkina, Lesn. Khoz. 12, 54 (1971); W. P. Smeljanez and L. A. Chursin, Anz. Schaedlingskd. 45, 33 (1972). 79. C. M. McKell, J. P. Blaisdell, J. R. Goodin, Eds., Wildland Shrubs-Their Biology and Utilization (General Technical Report INT-1, U.S. Forest Service, Washington, D.C., 1972). 80. C. H. A. Little, Can. J. Bot. 48, 1995 (1970). 81. S. J. Dina and L. G. Klikoff, J. Range Manage. 26, 207 (1973); J. D. Hodges and P. L. Lorio, Jr., Can. J. Bot. 47, 1651 (1969); see also Parker (84). 82. D. Otto, Arch. Forstwes. 19, 135 (1970). 83. W. Schwenke, Z. Angew. Entomol. 61, 365 (1968). 84. J. Parker, in Water Deficits and Plant Growth, T. T. Kozlowski, Ed. (Academic Press, New York, 1972), vol. 3, p. 125. 85. A. W. Naylor, in ibid., p. 241; R. E. Saunier, H. M. Hull, J. H. Ehrenreich, Plant Physiol. 43, 401 (1968). 86. T. C. R. White, Oecologia 16,279 (1974). 87. G. T. Harvey, Can. Entomol. 106, 353 (1974); see also Otto (82) and Schwenke (83). 88. T. T. Kozlowski, J. For. 67, 118 (1969); H. 0. Batzer, Environ. Entomol. 2, 727 (1973). 89. D. H. Janzen, Am. Nat. 104, 501 (1970); C. B. Huffaker, in Dynamics of Populations, P. J. denBoer and G. R. Gradwell, Eds. (Centre for Agricultural Publishing and Documentation, Wageningen, Netherlands, 1971), p. 327; J. R. Blais, For. Chron. 44 (1968).
639 citations
TL;DR: Studies using a variety of analogues and metabolites suggest that the structural features of butyric acid are rather stringently required for induction of erythroid differentiation.
630 citations
TL;DR: Duffy blood group negative human erythrocytes (FyFy) are resistant to infection by Plasmodium knowlesi, a simian malaria that infects Duffy positive human ERYthrocycles, which suggests that Duffy blood group determinants (Fya or Fyb) may be ery Throcyte receptors for P. vivax.
Abstract: Duffy blood group negative human erythrocytes (FyFy) are resistant to infection by Plasmodium knowlesi, a simian malaria that infects Duffy positive human erythrocytes. The P. knowlesi resistance factor, Duffy negative erythrocytes, occurs in high frequency in West Africa, where the people are resistant to vivax malaria. This suggests that Duffy blood group determinants (Fya or Fyb) may be erythrocyte receptors for P. vivax.
614 citations
TL;DR: The concentration of SRIF was highest in the median eminence and arcuate nucleus although all of the hypothalmic nuclei contained some fo this material, and the implications of this distribution are discussed.
Abstract: A sensitive and specific radioimmunoassay for somatostatin (SRIF) has been used to determine the regional distribution of SRIF in rat brain. The hypothalamus contained the highest concentration of SRIF. Lower, but significant amounts of SRIF were present outside of the hypothalamus. Within the hypothalamus, the concentration of SRIF was highest in the median eminence and arcuate nucleus although all of the hypothalamic nuclei contained some of this material. The implications of this distribution are discussed (Endocrinology96: 1456, 1975)
TL;DR: An epithelioid cell line, started from a human pancreatic carcinoma of ductal cell origin, has been maintained in culture for over 2 years and has been subcultured more than 40 times and has a modal number of 63 with three distinct marker chromosomes and a small ring chromosome.
Abstract: An epithelioid cell line, started from a human pancreatic carcinoma of ductal cell origin, has been maintained in culture for over 2 years and has been subcultured more than 40 times. The PANC-1 cell line has a doubling time of 52 h and G6PD activity of the slow mobility of B type. Chromosome studies show a modal number of 63 with three distinct marker chromosomes and a small ring chromosome. The malignant nature of the PANC-1 cell line was verified by: (1) the ready growth of PANC-1 cells in soft agar and on top of a fibroblast monolayer; and (2) the formation of a progressively growing anaplastic carcinoma after injection of a nude-athymic mouse with PANC-1 cells.
TL;DR: In this paper, 22 patients who had an episode of transfusion-associated hepatitis not positive for hepatitis B antigen were examined for development of antibody to heaptitis A and B antigens, cytomegalovirus and Epstein-Barr virus.
Abstract: Twenty-two patients who had an episode of transfusion-associated hepatitis not positive for hepatitis B antigen were examined for development of antibody to heaptitis A and B antigens, cytomegalovirus and Epstein-Barr virus. Antibody response to the 27-nm virus-like hepatitis A antigen was measured by immune electron microscopy. In none of the 22 patients studied did serologic evidence of infection with hepatitis A virus develop during the study period. Nine of the 22 patients had antibody responses to cytomegalovirus, but it was difficult to relate these seroconversions to their hepatitis. In addition, all 22 patients had pre-existing antibody to the Epstein-Barr virus. It seems likely that at least a proportion of such antigen-negative transfusion-associated hepatitis is caused by other infectious agents, not yet identified.
TL;DR: It appears that methyl neogenesis must normally play a role in both males and females when labile methyl intake is curtailed, and de novo formation of methyl groups is quantitatively more significant than ingestion of preformed methyl moieties.
Abstract: Normal young adult male and female subjects were maintained on fixed dietary regimens which were either essentially normal or were semisynthetic and curtailed in methionine and choline intakes and virtually free of cystine. The subjects maintained stable weights and remained in positive nitrogen balance or within the zone of sulfur equilibrium. Choline intakes were calculated, and urinary excretions of creatinine, creatine, and sacrosine were measured. Creatinine excretions of male subjects on essentially normal diets outweighed the total intakes of labile methyl groups. Taking into account the excretions of additional methylated compounds, as judged from published values, it appears that methyl neogenesis must normally play a role in both males and females. When labile methyl intake is curtailed, de novo formation of methyl groups is quantitatively more significant than ingestion of preformed methyl moieties. On the normal diets used in these experiments, the average homocysteinyl moiety in males cycled between methionine and homocysteine at least 1.9 times before being converted to cystathionine. For females, the average number of cycles was at least 1.5. When labile methyl intake was curtailed, the average number of cycles rose to 3.9 for males and 3.0 for females under the conditions employed.
TL;DR: The results indicate that recognition of a stimulus as familiar or novel is highly developed in monkeys, and that their difficulty with the customary nonspatial visual memory tasks stems from a retardation in noticing and using the mnemonic cue of recovery of presentation.
Abstract: Visual memory in monkeys was examined under four different conditions, each with a separate group. In all conditions, the delay between sample and choice was 10 sec, and the delay between trials was 30 sec. The procedural differences were matching or nonmatching with the same two objects presented repeatedly and matching or nonmatching with trial-unique objects. With the customary repetitive stimuli, whether in matching or nonmatching, most monkeys either required prolonged training to solve the problem (over 40 sessions) or failed to solve it, corroborating the learning difficulties reported earlier by others. With trial-unique stimuli, by contrast, most monkeys learned quickly (matching, under 20 sessions; nonmatching, under 5 sessions). Furthermore, in nonmatching with trial-unique stimuli, scores averaged 80% correct in the first session, even though the monkeys were experimentally naive. The results indicate that recognition of a stimulus as familiar or novel is highly developed in monkeys, and that their difficulty with the customary nonspatial visual memory tasks stems from a retardation in noticing and using the mnemonic cue of recovery of presentation. Evidence is presented that this difficulty can be overcome, however, by a simple training procedure that exploits their proficiency at distinguishing familiar from novel stimuli.
TL;DR: Twenty-seven patients with advanced diffuse histiocytic lymphoma (reticulum-cell sarcoma) were treated with combination chemotherapy utilising nitrogen mustard, procarbazine, vincristine, and prednisone and only one has had a recurrence of tumour.
TL;DR: A narrow-field, bistratified amacrine cell is the main subject of this study and it is hinted that in mammals even 'diffuse' cells terminate preferentially in certain sublayers of the IPL.
TL;DR: An enzymatic preparation from human brain converts tryptamine to tryptoline (9H-1,2,3, 4-tetrahydropyrido(3,4-b)indole) in the presence of 5-methyltetrahYDrofolic acid, which yields 1- methyltryptoline and 5-hydroxytryptoline, respectively.
Abstract: An enzymatic preparation from human brain converts tryptamine to tryptoline (9H-1,2,3,4-tetrahydropyrido(3,4-b)indole) in the presence of 5-methyltetrahydrofolic acid. Similarly, N-methyltryptamine and 5-hydroxytryptamine yield 1-methyltryptoline and 5-hydroxytryptoline, respectively. Neither in vitro nor in vivo formation of these compounds by human tissues has been described.
TL;DR: Six patients with a unique form of diabetes associated with extreme insulin resistance have markedly reduced insulin binding to specific receptors on their circulating monocytes, and when normal insulin receptors were exposed to serum or immunoglobulin fractions from three of these patients in vitro the specific binding defect was reproduced.
Abstract: Six patients with a unique form of diabetes associated with extreme insulin resistance have markedly reduced insulin binding to specific receptors on their circulating monocytes. When normal insulin receptors were exposed to serum or immunoglobulin fractions from three of these patients in vitro the specific binding defect was reproduced.
TL;DR: In this paper, an electro-optical system was developed to record microscope images with high resolution at low light intensities, which was used to study the invasion of erythrocytes by malaria merozoites.
Abstract: An electro-optical system was developed to record microscope images with high resolution at low light intensities The system was used to study the invasion of erythrocytes by malaria merozoites Invasion consists of attachment of the anterior end of the parasite to the erythrocyte, deformation of the erythrocyte, and the entry of the parasite by erythrocyte membrane invagination
TL;DR: The purification of tubulin and associated high-molecular-weight proteins, and the characteristics of microtubule polymerization in vitro are described.
Abstract: Explanations are required for the post-translational mechanisms that determine the initiation, growth, directionality, and spatial localization of microtubules. To analyze these problems experimentally, attempts have been made to establish polymerization systems in vitro in which the molecular components that regulate microtubule assembly might be identified. Because of the biochemical nature of this problem, brain tissue, which contains abundant microtubule protein, was chosen as the experimental material. Comparative biochemistry has shown that tubulin from diverse cell types has similar properties (see Olmsted and Borisy,' Stephens,? and Wilson and Bryan for reviews): therefore, the findings of studies on brain tubulin may be applicable to cytoplasmic microtubules in general. The purpose of this report is to describe the purification of tubulin and associated high-molecular-weight proteins, and the characteristics of microtubule polymerization in vitro. In this paper, we will discuss some of the factors that might be involved in the general regulation of the assembly process. Specifically, the following questions will be considered: (1) Are proteins other than tubulin associated with microtubules? (2) How do environmental conditions, such as ionic strength and pH, affect polymerization? ( 3 ) What role do nucleotides have in polymerization? (4) Do divalent cations inhibit or stimulate assembly? (5) Is tubule assembly in vitro an equilibrium process? (6) What is the overall mechanism of tubule assembly? (7) Are intermediates involved in the initiation and growth of tubules?
TL;DR: Now that the chemotherapeutic tools are sharpened, their use in combinations with other modalities in the previously unfamiliar setting of the patient with early stages of the disease promises to lead to an even more exciting chapter in clinical cancer research in the next decade.
Abstract: In a period of a little over 20 years, chemotherapy of cancer has evolved from a period of empiricism with little impact on the cancer problem to become part of a sound medical discipline with firm scientific underpinning playing an increasingly important role in the control of cancer. This progress has come from an increasing knowledge of cancer biology and pharmacology and the application of this knowledge to improved design of clinical trials, with due consideration to the intricacies of the natural history of each disease in question. Now that the chemotherapeutic tools are sharpened, their use in combinations with other modalities in the previously unfamiliar setting of the patient with early stages of the disease promises to lead to an even more exciting chapter in clinical cancer research in the next decade.
TL;DR: Gonadotropin binding and stimulation of cyclic adenosine 3':5'-monophosphate (cyclic AMP) formation and testosterone synthesis were studied in collagenase-dispersed interstitial cells from the adult rat testis Binding data were consistent with the presence of a single order of receptors, with no interaction between binding sites as mentioned in this paper.
TL;DR: It is suggested that Fv -1 may have a much broader inhibitory effect than previously recognized and support the replication of xenotropic MuLV to a limited extent.
TL;DR: Host suppressor cells may play a part in the decreased capacity of B lymphocytes to secret immunoglobulin in certain patients with myeloma.
Abstract: Since patients with myeloma have serious abnormalities of humoral immunity, we applied an in vitro assay to determine the capacity of B lymphocytes to mature into immunoglobulin-secreting cells. In peripheral blood lymphocytes from 22 normal persons, geometric mean immunoglobulin synthesis was 4910 ng for IgM, 1270 ng for IgA and 1625 ng for IgG. The synthesis rates of peripheral blood lymphocytes of 22 patients with myeloma were 458 ng for IgM, 321 ng for IgA and 218 ng for IgG. Circulating mononuclear cells from three of six patients tested suppressed polyclonal immunoglobulin synthesis by cocultured normal lymphocytes. Suppressive activity was not mediated by purified T cells alone. Removal of phagocytic mononuclear cells from lymphocyte populations of one patient nullified suppressive activity. Removal of phagocytic mononuclear cells from lymphocyte populations of a second patient led to a nearly 10-fold increase in polyclonal immunoglobulin synthesis. Therefore, host suppressor cells may pla...
TL;DR: A new parameter is proposed, the average affinity of the receptor sites, K, calculated as ( B F/(R o −B) , which has been successfully applied to the negative cooperativity of insulin receptors.
TL;DR: The meninges of various mammals were prepared for examination with the electronmicroscope by thin sectioning or freeze‐fracturing to determine the basis for the meningeal barrier between the blood circulating in dural vessels and the cerebrospinal fluid in the subarachnoid space.
Abstract: The meninges of various mammals were prepared for examination with the electronmicroscope by thin sectioning or freeze-fracturing. Particular attention was given to the distribution of tight junctions in order to determine the basis for the meningeal barrier between the blood circulating in dural vessels and the cerebrospinal fluid in the subarachnoid space. While some dural blood vessels are fenestrated, those in the subarachnoid space are not and their component endothelial cells are joined by an extensive system of tight junctions. An extensive and continuous system of tight junctions was also found in a layer of specialized cells at the border of the arachnoid with the dura. This arachnoid barrier layer is apparently the only basis of the meningeal barrier because often cellular layers in the dura and arachnoid lack tight junctions although they are linked by gap junctions and desmosomes. In particular, tight junctions are lacking at the border of the "subdural space" which is actually a fascial plane within the dura. Tight junctions are also lacking between astrocytes at the surface of the brain but these cells are linked by gap junctions and a new type of intercellular junction. The distribution of these junctions, as well as assemblies of intramembranous particles at the astrocytic border, raises the question whether this layer might have a role in the exchange of certain substances between the brain and cerebrospinal fluid.
TL;DR: It is reported here that phosphorylation of platelet myosin results in an increase in the actin-activatedMyosin ATPase activity measured at low ionic strength.
Abstract: HUMAN platelet myosin, which is similar to other myosins isolated from non-muscle cells, has a molecular weight of 460,000 and is composed of two heavy chains (200,000) and two different light chains (20,000 and 15,000)1–3. The 20,000 light chain can be phosphorylated by a kinase endogenous to human platelets3. This enzyme, which has been isolated and partially purified4, transfers 32P from γ-32P-ATP to the 20,000 light chain of platelet myosin in the presence of Mg2+. So far, the biological significance of this phosphorylation has been unknown, but we report here that phosphorylation of platelet myosin results in an increase in the actin-activated myosin ATPase activity measured at low ionic strength. Dephosphorylation of phosphorylated myosin results in a decrease in the actin-activated ATPase activity.