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Biomedical subjects

M Miller

Publications and source records attributed to M Miller.

At least 703 records · Page 39Linked to original sources

Assessment of hormonal disorders of water metabolism.

Clinical disorders of water regulation are relatively common and occur with severity ranging from profound and easily recognizable disturbance of body water balance to mild and often clinically inapparent. The development of sensitive and specific radioimmunoassay procedures capable of quantitating the level of AVP in plasma and urine has allowed elucidation of the pathophysiology of many of the disorders whether due to deficiency of ADH secretion and action or to excessive or persistent hormone release. In turn, the understanding of the factors regulating ADH release and action has led to establishment and validation of a variety of procedures that by indirect means allow estimation of extent of hormone action. These procedures based on physiologic influences that stimulate or inhibit ADH release or action are simple, readily available, and relatively inexpensive, and are capable of making an accurate diagnosis of a water-losing or water-retaining disorder. Properly performed and interpreted, such tests as water deprivation, saline infusion, comparison of urine and serum osmolality, and water loading can obviate the need for AVP immunoassays in evaluating most clinical disorders of water regulation. The immunoassay of AVP, although a valuable tool for the study of normal and pathologic physiology of ADH, is rarely necessary to firmly establish a clinical diagnosis and may itself be the source of misleading conclusions if its limitations are not fully appreciated.

Arginine Vasopressin↗

Preliminary x-ray analysis of single crystals of ovalbumin and plakalbumin.

Two crystal forms of hen ovalbumin have been grown and were characterized by x-ray diffraction. Crystals of ovalbumin grown at pH 5.4 are monoclinic, belonging to the space group C2 (a = 116.5 A, b = 41.8 A, c = 70.5 A, beta = 101.5 degrees). At pH 5.8 or higher ovalbumin forms triclinic crystals of space group P1 (a = 62.0 A, b = 84.3 A, c = 72.2 A, alpha = 87.4 degrees, beta = 103.9 degrees, gamma = 108.7 degrees). These crystals are usually small and difficult to grow reproducibly. Crystals of plakalbumin (a proteolytic modification of ovalbumin) are much easier to grow and appear suitable for three-dimensional structure determination. Their space group is C2 (a = 99.9 A, b = 102.0 A, c = 79.3 A, beta = 112.1 degrees) with two plakalbumin molecules in each asymmetric unit.

Animals↗

Lectin-resistant variants of mouse melanoma cells. II. In vitro characteristics.

Lectin-resistant variants of B-16 melanoma cells were selected with wheat-germ agglutinin, ricin and concanavalin A. They exhibited altered metastasizing capacity and tumorigenicity in C57BL mice. Several in vitro properties were defined and compared including homotypic adhesiveness, microfilament organization, melanin release, activity of tyrosine hydroxylase, DNA content, and karyotypes. The possible relevance of these properties in vitro for the malignant behavior displayed in vivo is discussed. The usefulness of this approach of selecting surface variants to study the problem of metastasis is also discussed.

Animals↗

Forskolin stimulation of acid and pepsinogen secretion by gastric glands.

Isolated gastric glands were used to investigate the action of forskolin, a novel diterpene extracted from the Indian plant Coleus forskohlii. Forskolin was found to stimulate both acid formation and pepsinogen secretion. The stimulation was rapid, reversible and dose dependent with an ED50 of approx. 1 microM. The efficacy of forskolin was similar to that of more commonly used secretagogues, e.g. histamine, carbachol, cyclic AMP derivatives. The responses to forskolin were not inhibited by any of the receptor-specific antagonists tested. Forskolin activated adenyl cyclase in gland homogenates over a dose range similar to that required for stimulation of secretory activity. Forskolin was found to be more effective in activating adenyl cyclase than histamine, isoproterenol or NaF. Treatment of gastric glands with forskolin resulted in a 100-fold increase in tissue cAMP levels, supporting the idea that forskolin activates adenyl cyclase in the intact cell. The results are interpreted to show that forskolin stimulation of gastric secretions is due to activation of adenyl cyclase with a consequent increase in tissue cAMP.

Animals↗

Absence of sleep-related elevation of growth hormone level in patients with stroke.

To determine the effect of defined suprahypothalamic lesions on sleep-related growth hormone (GH) secretion, eight patients with hemispheric lesions of vascular origin were studied in a sleep laboratory on two consecutive nights. Despite the normal onset and increased time spent in slow-wave sleep (SWS), the patients failed to show the nocturnal rise in plasma GH concentration that occurred in association with onset of SWS in five age-matched healthy subjects. Arginine hydrochloride infusion in the patients produced a normal GH rise, indicating integrity of the hypothalamic-pituitary axis. Dissociation between SWS and GH secretion in patients with suprahypothalamic damage suggests that cortical-subcortical structures are involved in the integration of SWS with nocturnal GH secretion. There is support for the presence of a thalamic regulatory center responsible for the control of GH release during sleep.

Aged↗

Hematological abnormalities in newborn infants with Down syndrome.

The hematological status of 81 infants with Down syndrome was reviewed retrospectively. Twenty babies had no hematological evaluation, 33 had a normal hematological status, and 28 had at least one abnormality, either of hematocrit, white cell count, or platelet count. Among these were 18 babies with increased hematocrit, one with decreased hematocrit, four with decreased platelet count, one with increased white cell count, three with increased hematocrit and decreased platelet count, and one with increased platelet count and increased white cell count. Some of these babies were evaluated for neoplasia or sepsis; however, in all the abnormal blood findings disappeared by 3 weeks without evidence of malignancy or infection. We conclude that hematological abnormalities with a benign natural history are common in Down syndrome infants.

Down Syndrome↗

Anaplastic thyroid cancer presenting with hyperthyroidism.

Primary thyroid malignancies typically do not interfere with thyroid function. A patient is reported with anaplastic thyroid carcinoma presenting with hyperthyroidism; this is believed to be the first such case described. Prior to the onset of the thyroidal process, the patient was clinically euthyroid. It is concluded that the mechanism of thyrotoxicosis is analogous to that of subacute thyroiditis: rapid tissue necrosis with resultant release of thyroid hormone.

Carcinoma↗

Extraamniotic infusion of prostaglandin F2 alpha in normal saline for termination of midtrimester missed abortion.

A combined method consisting of extraamniotic infusion of normal saline with prostaglandin F2 alpha was used in 20 patients for termination of midtrimester missed abortion. All 20 patients aborted within 12 h. The mean infusion abortion interval was 7.34 h. Side effects were observed only in 5 patients (25%), a low percentage when compared with other prostaglandin methods. The possibility of adjusting or stopping the infusion permitted the rapid control of side effects and the intensity of uterine contractions. According to the results obtained in this series, the proposed method seems to be more suitable than other procedures reported for termination of midtrimester missed abortion.

Abortion, Induced↗

Cholecystokinin-like immunoreactive neurons in rat cerebral cortex.

The distribution and form of cholecystokinin immunoreactive neurons in neocortical areas within the posterior pole of the rat cerebral hemisphere was examined using the immunoperoxidase technique. Although cholecystokinin-positive neurons are present throughout the cortex, they are most frequent in the supragranular layers. These neurons are of three kinds: layer I neurons, bipolar cells, and other non-pyramidal cells with either multipolar or bitufted dendritic trees. In electron-microscopic preparations, the horseradish peroxidase reaction product is found to form a granular deposit which occurs throughout the cytoplasm and nucleoplasm and shows no predilection for any particular type of organelle. Electron-microscopy also shows cholecystokinin-positive neurons to have both symmetric and asymmetric synapses on their perikarya, which is additional evidence in favor of the interpretation that they are non-pyramidal cells. In the light-microscopic preparations three types of CCK-positive axons are encountered. These are vertically-oriented axons considered to arise from bipolar cells, a plexus in the superficial portion of layer II/III which is believed to arise from the multipolar and bitufted cells, and a deep plexus of unknown origin in layers VI and V. Since the axons of bipolar cells form asymmetric synapses they are thought to be excitatory neurons. In contrast, the bitufted and multipolar neurons are probably inhibitory, for previous studies have shown neurons with similar features to have axons which form symmetric synapses and to contain glutamic acid decarboxylase. Thus, although iontophoretically-applied cholecystokinin excites cortical neurons, it appears to be present in some neurons which are excitatory and others which are inhibitory.

Animals↗

Active site of RNase: neutron diffraction study of a complex with uridine vanadate, a transition-state analog.

A complex of RNase A with a transition-state analog, uridine vanadate, has been studied by a combination of neutron and x-ray diffraction. The vanadium atom occupies the center of a distorted trigonal bipyramid, with the ribose oxygen O2' at the apical position. Contrary to expectations based on the straightforward interpretation of the known in-line mechanism of action of RNase, nitrogen NE2 of histidine-12 was found to form a hydrogen bond to the equatorial oxygen O8, while nitrogen NZ of lysine-41 makes a clear hydrogen bond to the apical oxygen O2'. Nitrogen ND1 of histidine-119 appears to be within a hydrogen-bond distance of the other apical oxygen, O7. Two other hydrogen bonds between the vanadate and the protein are made by nitrogen NE2 of glutamine-11 and by the amide nitrogen of phenylalanine-120. The observed geometry of the complex may necessitate reinterpretation of the mechanism of action of RNase.

Animals↗

Gastric contents at induction of anaesthesia. Is a 4-hour fast necessary?

The study was undertaken to ascertain whether a light standard breakfast would influence the volume and median pH of gastric contents. Comparisons were obtained between a group of patients (n = 22) fasted overnight and a group (n = 23) allowed a light breakfast. There were no significant differences between the groups in respect of the volume of gastric contents aspirated, the median pH of the gastric contents or the number of patients with a pH of less than 3.0 unit.

Adult↗

Uptake of L-[14C]proline by isolated rat brain capillaries.

Rat brain capillaries exhibit concentrative uptake of L-proline. The uptake is mediated by two saturable systems, one with a Km of 0.11 mM and another with a Km of 5.9 mM. Entry also occurred by diffusion, especially at high substrate concentrations. The saturable high-affinity system is sodium-dependent, with a Km for sodium of 36 mM. Proline uptake is not inhibited by lysine, but is inhibited by phenylalanine, glycine, and leucine. alpha-Methylaminoisobutyric acid (MeAIB), a model for sodium-requiring transport systems, is a competitive inhibitor of the low-Km system. b-2-Aminobicyclo-[2,2,1]-heptane-2-carboxylic acid (BCH), a model for nonsodium-dependent transport, however, also inhibited proline uptake.

Animals↗