bluuebunny/crossref_metadata_2025 huggingface dataset:
The Differential Role of Motor Cortex in Stretch Reflex Modulation Induced by Changes in Environmental Mechanics and Verbal Instruction
Authors: Shemmell Jonathan , An Je Hi , Perreault Eric J.
Published: October 2009

The motor cortex assumes an increasingly important role in higher mammals relative to that in lower mammals. This is true to such an extent that the human motor cortex is deeply involved in reflex regulation and it is common to speak of “transcortical reflex loops.” Such loops appear to add flexibility to the human stretch reflex, once considered to be immutable, allowing it to adapt across a range of functional tasks. However, the purpose of this adaptation remains unclear. A common proposal is that stretch reflexes contribute to the regulation of limb stability; increased reflex sensitivity during tasks performed in unstable environments supports this hypothesis. Alternatively, before movement onset, stretch reflexes can assist an imposed stretch, opposite to what would be expected from a stabilizing response. Here we show that stretch reflex modulation in tasks that require changes in limb stability is mediated by motor cortical pathways, and that these differ from pathways contributing to reflex modulation that depend on how the subject is instructed to react to an imposed perturbation. By timing muscle stretches such that the modulated portion of the reflex occurred within a cortical silent period induced by transcranial magnetic stimulation, we abolished the increase in reflex sensitivity observed when individuals stabilized arm posture within a compliant environment. Conversely, reflex modulation caused by altered task instruction was unaffected by cortical silence. These results demonstrate that task-dependent changes in reflex function can be mediated through multiple neural pathways and that these pathways have task-specific roles.
Kv7/KCNQ Channels Control Action Potential Phasing of Pyramidal Neurons during Hippocampal Gamma OscillationsIn Vitro
Authors: Leão Richardson N. , Tan Hui Min , Fisahn André
Published: October 2009

While the synaptic mechanisms involved in the generation ofin vitronetwork oscillations have been widely studied, little is known about the importance of voltage-gated currents during such activity. Here we study the role of the M-current (IM) in the modulation of network oscillations in the gamma-frequency range (20–80 Hz). Kv7/KCNQ subunits, the molecular correlates ofIM, are abundantly expressed in CA1 and CA3 pyramidal neurons, andIMis an important modulator of pyramidal neuron firing. Using hippocampal slices, we recorded field activity and pyramidal neuron action potential timing during kainate-induced gamma oscillations. Application of the specificIMblocker XE991 causes a significant reduction of gamma oscillation amplitude with no significant change in oscillation frequency. Concomitant CA3 pyramidal neuron recordings show a significant increase in action potential frequency during ongoing gamma oscillations after the application of XE991. This increase is associated with a significant loss of periodicity of pyramidal neuron action potentials relative to the phase of the gamma oscillations. Using dynamic clamp, we show thatIMacts to improve the periodicity of action potential timing and to decrease action potential frequency. We further validate these results in a compartmental model of a pyramidal neuron. Our work suggests thatIMmodulates gamma oscillations by regulating the phasing of action potential firing in pyramidal neurons.
Relationship between Neural Responses and Visual Grouping in the Monkey Parietal Cortex
Authors: Yokoi Isao , Komatsu Hidehiko
Published: October 2009

Visual grouping through the binding of multiple discrete elements is an important component of object perception, and neurological studies have shown that the posterior parietal cortex plays a vital role in that process. To study the neural mechanisms underlying visual grouping, we recorded neuronal activity from the lateral bank of the intraparietal sulcus (L-IPS) of monkeys while they performed a task that required them to discriminate among rapidly presented visual patterns composed of five black or white dots arranged in a cross. The monkeys had to detect the patterns in which dots with the same contrast were arranged either horizontally or vertically (target). Visual grouping was necessary for detection of the target, and we surmised that if L-IPS neurons are involved in visual grouping, they may selectively respond to the grouped objects. In addition, we manipulated the monkeys' attention to the grouping of the elements. We found that many L-IPS neurons showed selectivity for the orientation of the target stimuli, and that selectivity was enhanced by the top-down attention. Moreover, the selectivity correlated with behavioral performance. These results provide the first physiological evidence that L-IPS neurons make a crucial contribution to visual grouping by combining visual and attentional signals so as to bind discrete visual elements together.
Muscle Contractions Guide Rohon–Beard Peripheral Sensory Axons
Authors: Paulus Jeremiah D. , Willer Gregory B. , Willer Jason R. , Gregg Ronald G. , Halloran Mary C.
Published: October 2009

Multiple molecular cues guide neuronal axons to their targets during development. Previous studiesin vitrohave shown that mechanical stimulation also can affect axon growth; however, whether mechanical force contributes to axon guidancein vivois unknown. We investigated the role of muscle contractions in the guidance of zebrafish peripheral Rohon–Beard (RB) sensory axonsin vivo. We analyzed several mutants that affect muscle contraction through different molecular pathways, including a new mutant allele of thetitin a (pik)gene, mutants that affect the hedgehog signaling pathway, and a nicotinic acetylcholine receptor mutant. We found RB axon defects in these mutants, the severity of which appeared to correlate with the extent of muscle contraction loss. These axons extend between the muscle and skin and normally have ventral trajectories and repel each other on contact. RB peripheral axons in muscle mutants extend longitudinally instead of ventrally, and the axons fail to repel one another on contact. In addition, we showed that limiting muscle movements by embedding embryos in agarose caused similar defects in peripheral RB axon guidance. This work suggests that the mechanical forces generated by muscle contractions are necessary for proper sensory axon pathfindingin vivo.
Ventral Striatal Neurons Encode the Value of the Chosen Action in Rats Deciding between Differently Delayed or Sized Rewards
Authors: Roesch Matthew R. , Singh Teghpal , Brown P. Leon , Mullins Sylvina E. , Schoenbaum Geoffrey
Published: October 2009

The ventral striatum (VS) is thought to serve as a gateway whereby associative information from the amygdala and prefrontal regions can influence motor output to guide behavior. If VS mediates this “limbic–motor” interface, then one might expect neural correlates in VS to reflect this information. Specifically, neural activity should reflect the integration of motivational value with subsequent behavior. To test this prediction, we recorded from single units in VS while rats performed a choice task in which different odor cues indicated that reward was available on the left or on the right. The value of reward associated with a left or rightward movement was manipulated in separate blocks of trials by either varying the delay preceding reward delivery or by changing reward size. Rats' behavior was influenced by the value of the expected reward and the response required to obtain it, and activity in the majority of cue-responsive VS neurons reflected the integration of these two variables. Unlike similar cue-evoked activity reported previously in dopamine neurons, these correlates were only observed if the directional response was subsequently executed. Furthermore, activity was correlated with the speed at which the rats' executed the response. These results are consistent with the notion that VS serves to integrate information about the value of an expected reward with motor output during decision making.
Nonlinear Integration of Visual and Haltere Inputs in Fly Neck Motor Neurons
Authors: Huston Stephen J. , Krapp Holger G.
Published: October 2009

Animals use information from multiple sensory organs to generate appropriate behavior. Exactly how these different sensory inputs are fused at the motor system is not well understood. Here we study how fly neck motor neurons integrate information from two well characterized sensory systems: visual information from the compound eye and gyroscopic information from the mechanosensory halteres. Extracellular recordings reveal that a subpopulation of neck motor neurons display “gating-like” behavior: they do not fire action potentials in response to visual stimuli alone but will do so if the halteres are coactivated. Intracellular recordings show that these motor neurons receive small, sustained subthreshold visual inputs in addition to larger inputs that are phase locked to haltere movements. Our results suggest that the nonlinear gating-like effect results from summation of these two inputs with the action potential threshold providing the nonlinearity. As a result of this summation, the sustained visual depolarization is transformed into a temporally structured train of action potentials synchronized to the haltere beating movements. This simple mechanism efficiently fuses two different sensory signals and may also explain the context-dependent effects of visual inputs on fly behavior.
Task-Dependent Activations of Human Auditory Cortex during Pitch Discrimination and Pitch Memory Tasks
Authors: Rinne Teemu , Koistinen Sonja , Salonen Oili , Alho Kimmo
Published: October 2009

The functional organization of auditory cortex (AC) is still poorly understood. Previous studies suggest segregation of auditory processing streams for spatial and nonspatial information located in the posterior and anterior AC, respectively (Rauschecker and Tian, 2000; Arnott et al., 2004; Lomber and Malhotra, 2008). Furthermore, previous studies have shown that active listening tasks strongly modulate AC activations (Petkov et al., 2004; Fritz et al., 2005; Polley et al., 2006). However, the task dependence of AC activations has not been systematically investigated. In the present study, we applied high-resolution functional magnetic resonance imaging of the AC and adjacent areas to compare activations during pitch discrimination and n-back pitch memory tasks that were varied parametrically in difficulty. We found that anterior AC activations were increased during discrimination but not during memory tasks, while activations in the inferior parietal lobule posterior to the AC were enhanced during memory tasks but not during discrimination. We also found that wide areas of the anterior AC and anterior insula were strongly deactivated during the pitch memory tasks. While these results are consistent with the proposition that the anterior and posterior AC belong to functionally separate auditory processing streams, our results show that this division is present also between tasks using spatially invariant sounds. Together, our results indicate that activations of human AC are strongly dependent on the characteristics of the behavioral task.
Functional Recovery after Lesion of a Central Pattern Generator
Authors: Sakurai Akira , Katz Paul S.
Published: October 2009

In cases of neuronal injury when regeneration is restricted, functional recovery can occur through reorganization of the remaining neural circuitry. We found an example of such recovery in the central pattern generator (CPG) for the escape swim of the molluscTritonia diomedea. The CPG neurons are bilaterally represented and each neuron projects an axon through one of two pedal commissures. Cutting the posterior pedal commissure [pedal nerve 6 (PdN6)] in the animal or in the isolated brain caused a deficit in the swim behavior and in the fictive motor pattern, respectively, each of which recovered over the course of 20 h. Locally blocking spiking activity in PdN6 with sodium-free saline and/or tetrodotoxin disrupted the motor pattern in a reversible manner. Maintained blockade of PdN6 led to a functional recovery of the swim motor pattern similar to that observed in response to cutting the commissure. Among the CPG neurons, cerebral neuron 2 (C2) makes functional connection onto the ventral swim interneuron-B (VSI) in both pedal ganglia. Cutting or blocking PdN6 eliminated C2-evoked excitation of VSI in the pedal ganglion distal to the lesion. Associated with the recovery of the swim motor pattern, the synaptic action of C2 onto VSI in the proximal pedal ganglion changed from being predominantly inhibitory to being predominantly excitatory. These results show that theTritoniaswim CPG undergoes adaptive plasticity in response to the loss of critical synaptic connections; reversal of synaptic action in the CPG may be at least partially responsible for this functional recovery.
F-BAR Proteins of the Syndapin Family Shape the Plasma Membrane and Are Crucial for Neuromorphogenesis
Authors: Dharmalingam Elavarasi , Haeckel Akvile , Pinyol Roser , Schwintzer Lukas , Koch Dennis , Kessels Michael Manfred , Qualmann Britta
Published: October 2009

Coordinated functions of the actin cytoskeleton and microtubules, which require careful control in time and space, are indispensable for the drastic alterations of neuronal morphology during neuromorphogenesis and neuronal network formation. Actin filament formation driven by the Arp2/3 complex and its activator neural Wiskott-Aldrich syndrome protein (N-WASP) is important for proper axon development. The underlying molecular mechanisms for targeting to and specific activation of N-WASP at the neuronal plasma membrane, however, have thus far remained elusive. We show that syndapin I is critical for proper neuromorphogenesis and hereby uses N-WASP as a cytoskeletal effector. Upon N-WASP binding, syndapins release N-WASP autoinhibition. Syndapins hereby cooperate with Cdc42 and phosphatidyl-inositol-(4,5)-bisphosphate. Syndapins furthermore specifically bind to phosphatidylserine-containing membranes via their extended F-BAR domain. Dissecting the syndapin functions actin nucleation and direct membrane bindingin vivo, we demonstrate that both functions are physiologically relevant and required. Constitutive plasma membrane-targeting experimentsin vivoindicate that specifically actin nucleation at the cell cortex is triggered by syndapins. Consistent with syndapins steering N-WASP as downstream effector for cortical actin nucleation, syndapin-induced neuronal arborization is N-WASP and Cdc42 dependent. The functions of syndapin–N-WASP complexes in neuromorphogenesis were revealed by loss-of-function studies. Knockdown of syndapin I leads to impaired axon development and especially phenocopies the aberrant axon branching observed upon N-WASP and Arp2/3 complex deficiency. In contrast, proper length control involves another N-WASP-binding protein, Abp1. Our data thus reveal that syndapin I is crucial for neuromorphogenesis and that different N-WASP activators ensure fine control of N-WASP activity and have distinct functions during neuronal network formation.
Electoral Reform and Party System Development in Japan and Taiwan: A Comparative Study
Authors: Jou Willy
Published: October 2009

This article examines changes in patterns of party competition in Japan and Taiwan following the introduction of mixed parallel electoral systems. National and district level election results demonstrate the consolidation of a two-party system in both countries. Differences in the speed and extent of this development are analyzed.
Russia's Search for Influence in Southeast Asia
Authors: Rangsimaporn Paradorn
Published: October 2009

This article examines Russia's relations with Southeast Asia and ASEAN, analyzing in particular the increased attempts under President Vladimir Putin to assert Russian influence in this sub-region. It looks at how Southeast Asia and ASEAN are important for Russia in its aspirations to become a major regional player.
Russia and North Korea: Dilemmas and Interests
Authors: Buszynski Leszek
Published: October 2009

Russia had two objectives in its relationship with North Korea. One was denuclearization and the other was to promote influence on the Korean Peninsula to balance the U.S. and Japan. Denuclearization has failed, and Russia will adjust to a nuclear North Korea to further its second aim.
Normalizing Japan: Supporter, Nuisance, or Wielder of Power in the North Korean Nuclear Talks?
Authors: Hagström Linus
Published: October 2009

This article demonstrates how Tokyo has been exercising economic power in the multilateral talks on North Korea, including over the U.S. The implication is that Japanese foreign and security policy can be regarded as "normal" already---hence forming a critique of ideas of "normalization" that are preconditioned on remilitarization.
The Limits of Ngo-Government Relations in South Korea
Authors: Kim Euiyoung
Published: October 2009

NGOs have been a major actor in South Korea's democratic governance and have sometimes played key roles in cooperation with the government. However, their once prominent status is in decline, attributed here to their structural weakness, over-politicization, and the risk of being potentially co-opted by the government
STUDIES ON OESTROGEN METABOLISM IN NEWBORN BOYS
Authors: Tillinger K.-G. , Diczfalusy E. , Westman A.
Published: October 2009

Attempts have been made to measure the excretion of oestrone, oestradiol-17β and oestriol in urine specimens collected from newborn boys. Only oestriol was found in measurable amounts. The excretion of oestrone and oestradiol-17β was found to be beyond the sensivity of the method (i.e. less than 1.5 μg.l litre urine), even following the administration of human chorionic gonadotrophin (HCG) or of oestradiol-17β. These findings will be discussed in relation to the oestrogen metabolism in the human fetus.
THE METABOLIC AND CLINICAL EFFECTS OF A NEW SERIES OF DELTA 1, 4-DIENE STEROIDS
Authors: Pechet Maurice M.
Published: October 2009

A series of delta 1, 4-diene steroids were studied in Normal, Addisonian and Arthritic subjects. Their metabolic effects were compared with those of the parent steroids. The following were studied: prednisone (Meti E) and cortisone (E); prednisolone (Meti F) and hydrocortisone (F); Meti B and corticosterone (B); Meti S and 17 hydroxy doc; Meti doca and Doca; Meti FF and 9 alpha fluoro-hydrocortisone; Meti U; Meti A. Thirty and seventy mg. Meti E and Meti F produced in normal subjects sodium loss, compared to sodium retention with 150 to 280 mg. of E and F. The presence of the extra double bond in Meti E and Meti F is associated with enhanced eosinopenic, anti-anabolic and anti-inflammatory properties; however, tubular reabsorption of sodium is not correspondingly increased – this difference, of a quantitative nature, is best explained on the basis of a glomerulo-tubular imbalance. Tubular reabsorption of sodium was not enhanced with the introduction of a double bond in the 1, 2 position, in the parent steroids: Doca, S, A and B. Meti E and Meti F produce the characteristic transitory potassium diuresis on starting, and retention on stopping medication, as did E and F. Meti B has marked eosinopenic properties, in contrast to B. Meti FF has enhanced eosinopenic properties over FF; however, tubular reabsorption of sodium is of a similar magnitude. Studies of absorption and excretion showed that the Meti steroids differ markedly from the parent steroids, in: (1) prolongation of the half-life; (2) conversion to 17 ketosteroids, to a very limited extent; (3) excretion mainly in the free unconjugated form.

The actions of Meti E and Meti F are qualitatively similar, albeit quantitatively greater than, those of E and F, with the notable exception that tubular reabsorption of sodium in man is less.
FURTHER EXPERIENCES WITH NITROGEN-CONTAINING STEROIDS FROM AQUEOUS ADRENAL EXTRACTS
Authors: Schroeder W. , Voigt K. D.
Published: October 2009

Nitrogen-containing steroids were isolated from aqueous adrenal cortical extracts. After fractionation by paper electrophoresis and counter-current distribution 17 bands fulfill the criteria for nitrogen and steroid (Voigt & Schroeder, Acta endocrinol. 21, 343, 1956). The original substances are partially active in maintaining adrenalectomized animals, but the final fractions with a Δ4,3-one configuration are partly inactive in this test. Therefore further biological assays were performed: the life-maintaining activity and the influence on the metabolism of electrolytes, nitrogen and lipids in the adrenalectomized golden hamster and dog. Other experiments concern the effect of adrenal cortical hormones on the metabolism of the liver.
GRADIENT ELUTION CHROMATOGRAPHY OF URINARY 17-KETOSTEROIDS
Authors: Vestergaard Per
Published: October 2009

New techniques have been developed for the assay by gradient elution chromatography of individual 17-ketosteroids.

Inexpensive and easily constructed apparatus is used in the assay.

The techniques are particularly suited for serial assays and for laboratories interested in doing many assays per day, but can be set up also without special equipment in laboratories planning to do only a few assays at a time.

Data are given from a normal material and findings from some systematic studies of details of the method are reported.
HYDROLYSIS OF 17-KETOSTEROID CONJUGATES WITH A PROCEDURE BASED ON SIMULTANEOUS BENZENE EXTRACTION AND ACID HYDROLYSIS
Authors: Vestergaard Per , Claussen Borge
Published: October 2009

A comparison of a hydrolytic method based on simultaneous benzene extraction and acid hydrolysis with methods using acid hydrolysis followed by extraction with an organic solvent has confirmed the superiority claimed for the simultaneous benzene extraction by other investigators. Less transformation, artefact formation and destruction was found with the simultaneous extraction method.

A fractionated hydrolytic procedure performed at different pH values is proposed for the simultaneous benzene extraction technique. This procedure gives best protection to the acid and heat labile 17-ketosteroids and highest yields of individual 17-ketosteroids.

The usefulness of this procedure in itself and in combination with β-glucuronidase hydrolysis has been explored.

It was found that a method employing simultaneous benzene extraction and acid hydrolysis after β-glucuronidase hydrolysis gave slightly higher yields overall and for some individual 17-ketosteroids than any other method examined.

It is suggested that the simple hydrolytic method based on simultaneous benzene extraction and acid hydrolysis alone may well be the preferred method for clinical assay at the present time. Its speed, simplicity and inexpensiveness together with its independence of enzyme inhibitors and other factors affecting the enzyme assay may for such an application outweigh the lower yield obtained for 11-oxy 17-ketosteroids.
IN VITRO STUDIES OF THYROID FUNCTION WITH ERCTHROCYTE UPTAKE OF 131I-LABELED-L-TRIIODOTHYRONINE
Authors: Yen Wang
Published: October 2009

1. ABSTRACT

The basic technique developed by others for measuring the uptake of 131I-labeled-triiodothyronine (131I-T3) by erythrocytes has been investigated and evaluated, and a modified procedure had been adopted which increases the reliability, reproducibility, and simplicity of the test.

Contrary to the reports of other workers, variations in original hematocrit were found to have no significant effect on erythrocyte uptake. However, the concentration of plasma proteins was found to be a significant factor influencing EU.

The mechanism of EU was investigated. The uptake appears to be a measurement of the interaction between two specific protein fractions and thyroid hormones in the plasma. One tends to decrease erythrocyte uptake activity and the other to increase it. These two protein fractions would therefore be very important in influencing thyroid hormone metabolism. The increased EU values in the hyperthyroidism also could be partly due to the fact that the increased concentration of thyroxine in the serum displaces T3 from the thyroxine-binding-globulin, whereby the T3-uptake in the erythrocytes is increased.
COMPARISON OF FIVE METHODS FOR THE EXTRACTION OF HUMAN PITUITARY GONADOTROPHIN FROM URINE
Authors: Borth Rudi , Menzi Annette
Published: October 2009

Thirty samples of pooled urine from hospitalized postmenopausal women, normally menstruating women and hospitalized men were extracted for gonadotrophin by the following five methods: I. The tannic acid method of Johnsen (1958); II. the kaolin-acetone method of Albert (1955) as modified by Borth et al. (1961); III. the kaolin-acetone method of Loraine & Brown (1959); IV. the ethanol precipitation-dialysis method of Klinefelter et al. (1943); and V. the benzoic acid-tungstic acid method of Butt (1958). The extracts were assayed for gonadotrophic activity by the mouse uterus test in terms of the International Reference Preparation for Human Menopausal Gonadotrophin, using Pergonal® (Istituto Farmacologico Serono, Rome, Italy) as a standard.

The five types of extract were compared with regard to yield of gonadotrophin, purity, toxicity, and behaviour in bioassay, using statistical methods to assess the significance of results.

Differences in slope of dose-response lines, standard deviation of response and precision of estimates were negligible.

Marked and strongly correlated differences were noted in purity and toxicity, the former decreasing, the latter increasing in the following order: Method I, II, V, IV, III.

Differences in yield were negligible for the extracts from high-titre urines, except for Method V which gave a lower yield. For the extracts from low-titre urines, the yields differed markedly, decreasing in the following order: Method I, III, IV, II, V. The most likely conclusion from the evidence available was to attribute the differences in yield to the presence of different amounts of otherwise inert substances which – depending on local conditions and experimental details – interfered with the response of test animals. Incomplete extraction was thought to be partly responsible only for the low yields obtained by Method V from both types of urine.

Based on the results of this study, Method I was adopted as a routine procedure.

Fiducial limits of slope were calculated both from the inter-assay and from the intra-assay variation. The two fiducial intervals were in excellent agreement, thus confirming part of the assumptions underlying the statistics of bioassay.
COMPARISON OF THE CLINICAL AND STEROID METABOLIC EFFECT OF HUMAN PITUITARY- AND URINARY GONADOTROPHINS IN AMENORRHOEIC WOMEN
Authors: Diczfalusy E. , Johannisson Elisabeth , Tillinger K.-G. , Bettendorf G.
Published: October 2009

A human hypophysial gonadotrophin (HHG) and three human menopausal gonadotrophin (HMG) preparations were administered to 6 amenorrhoeic women for 8 to 10 days in 19 experiments. This was followed by daily injections of human chorionic gonadotrophin (HCG) for 4 days. The clinical and steroid metabolic effects of the preparations were assessed by serial endometrial biopsies, daily vaginal smears and by the determination of urinary oestrone, 17β-oestradiol, oestriol, pregnane3α,20α-diol, 17-ketosteroids and 17-hydroxycorticosteroids in 48-hour samples.

There was a four-fold difference in the follicle stimulating hormone (FSH) activity of two commercial HMG preparations, although their »total gonadotrophin« activity was identical.

The clinical effectiveness of the various gonadotrophin preparations was found to be a function of the amount of FSH– rather than »total gonadotrophic« activity administered.

When a total dose of some 15 000 International Reference Preparation (I. R. P.) units of FSH activity of whatever origin was administered prior to HCG, there was invariably a marked clinical and steroid metabolic effect, suggesting very strongly that ovulation had indeed been induced. In such experiments the urinary oestrogen and pregnanediol excretion always significantly exceeded the values found in non-pregnant women. Four patients attempted to conceive during the period when ovulation was presumed to occur. Two of them became pregnant; one delivered a normal child, the other aborted in the third month of gestation.

It is concluded that in addition to human hypophysial gonadotrophins, human menopausal gonadotrophin preparations in combination with HCG are also completely satisfactory for the induction of ovulation in amenorrhoeic women. A prerequisite for the successful clinical use of such preparations is, however, adequate information on their specific FSH (and perhaps also ICSH) activity.
THE OESTROGENIC AND ANTI-OESTROGENIC ACTIVITY OF COMPOUNDS RELATED TO DIETHYLSTILBOESTROL
Authors: Emmens C. W. , Cox R. I. , Martin L.
Published: October 2009

The activities of some dihydroxyphenylalkanes in mice have been compared with those of dihydroxyphenylalkenes already investigated. All are both pro-oestrogenic and anti-oestrogenic, the latter when applied to the vagina in much less than the pro-oestrogenic dose. Peak anti-oestrogenic activity is seen in the dimethyl substituents of both series (dimethylstilboestrol and meso-butoestrol).

The other alkanes showed no detectable oestrogenic activity in subcutaneous doses of up to 5 mg in oil in vaginal smear tests, but some activity in intravaginal tetrazolium reduction tests in doses of less than 1 mg, although with very shallow dose-response lines. The same compounds were weakly anti-oestrogenic and did not interfere with early pregnancy in daily doses of 2 mg.

The high correlation between pro-oestrogenic, anti-oestrogenic and antifertility potencies in these compounds makes it hazardous to ascribe the latter action to either of the former without further evidence.
FACTORS DETERMINING CESSATION OF CORPUS LUTEUM FUNCTION; THE POSSIBLE ROLE OF OESTRADIOL AND PROGESTERONE
Authors: de Jongh S. E. , Wolthuis O. L.
Published: October 2009

The role of oestrogen and progesterone utilization by the uterus was investigated with regard to the mechanism of cessation of corpus luteum function. After the administration of oestradiol benzoate with or without progesterone in various combinations to spayed, spayed-hysterectomized, or spayed traumatized rats it was found that:

there were no percentage differences in the oestrogenic effects in the vaginal smears of spayed or spayed-hysterectomized rats after the administration of oestradiol benzoate alone.

After treatment with combinations of oestradiol and progesterone, the oestrogenic effects were inhibited in spayed-hysterectomized animals as compared with similarly treated spayed controls. A still more marked inhibition was obtained after traumatizing the uterine endometrium.

Increasing doses of progesterone in combination with a fixed dose of oestradiol benzoate progressively delayed vaginal opening.

It is concluded that the uterus does not utilize any measurable amounts of oestrogen, but that, on the other hand, it does utilize considerable quantities of progesterone. Traumatization of the uterus may have a similar progesterone-sparing effect. The findings are discussed against the background of factors which determine cessation of corpus luteum function, while it is suggested that progesterone may be an important factor accounting for the effects of hysterectomy.
DIFFERENT MODES OF ACTION OF TWO ANTIOVULATORY COMPOUNDS
Authors: Overbeek G. A. , de Visser J.
Published: October 2009

Lynestrenol and 6α-methyllynestrenol were studied in rats for their respective ability to:

prevent spontaneous ovulation.

prevent ovulation induced by a single injection of luteinizing hormone (human chorionic gonadotrophin).

to prevent ovarian hypertrophy in parabiotic (♀[unk]) rats

The results warrant the following conclusions about the site of action of both substances:

Lynestrenol prevents ovulation by inhibiting FSH release from the pituitary gland, so that there are no ripening follicles ready to respond to LH.

6α-Methyllynestrenol inhibits ovulation by abolishing LH-release thus preventing the final maturation and rupture of normally developing follicles.
EFFECTS OF OESTROUS CYCLE VARIATIONS AND EXOGENOUS STEROID HORMONES ON THE PRODUCTION AND SECRETION OF CORTICOSTERONE BY THE RAT ADRENAL
Authors: Pincus Gregory , Hirai Masanao
Published: October 2009

Results with the adrenal gland:

A significant difference (P < 0.01) was found between the elevated production of corticosterone in intact rats during dioestrus and the production at oestrus.

At both 10 and 20 days after ovariectomy, the production of corticosterone was decreased as compared with the dioestrous rate.

Production of corticosterone in adrenals was increased significantly (P < 0.01) by progesterone injection (500 μg/day for 5 days) and was decreased by oestradiol-17β injections 5 μg/day for 5 days).

Corticosterone injection (10 μg/day for 5 days) also significantly (P < 0.01) increased the production of corticosterone in adrenals.

Results with adrenal vein blood:

Secretion of corticosterone of the intact rat at dioestrus was higher than at oestrus, but the difference was not statistically significant.

At 10 and 20 days after ovariectomy, the secretion of corticosterone had decreased from the dioestrous level, but statistical significance was found only at 20 days after ovariectomy.

Oestradiol-17β treatment (5 μg/day for 5 days) significantly (P < 0.01) decreased the secretion of corticosterone from the adrenal vein.

Progesterone treatment (500 μg/day for 5 days) did not significantly affect the secretion of corticosterone into adrenal vein blood. Also, treatment with corticosterone (10 μg/day for 5 days) did not yield statistically significant changes in the secretion of this compound.

Additional results:

Nembutal anaesthesia in intact male rats significantly decreased the amount of corticosterone in the adrenal gland (P < 0.05). Ether anaesthesia led to a greater variation in adrenal corticosterone than in nonanaesthetized rats.

Ovary weights decreased significantly (P < 0.05) in the progesteroneinjected group (500 μg/day for 5 days); on the other hand, the oestradiol-17β-injected group (5 μg/day for 10 days) exhibited a significant increase of adrenal weight (P < 0.05), and pituitary weight (P < 0.01) and a decrease of ovary weight (P < 0.05).
LACK OF EFFECT OF CORTICOSTEROIDS ON THE IN VIVO DISAPPEARANCE OF SULFHYDRYL-INHIBITED AND ANTIBODY-COATED ERYTHROCYTES
Authors: Agarwal Kailash N.
Published: October 2009

Red cells were incubated in vitro with sulfhydryl inhibitors and Rhantibody with and without prior incubation with prednisolone-hemisuccinate.

These erythrocytes were labelled with Cr51 and P32 and their disappearance in vivo after autotransfusion was measured.

Prior incubation with prednisolone-hemisuccinate had no effect on the rate of red cell disappearance. The disappearance of the cells was shown to take place without appreciable intravascular destruction.
UPTAKE OF CORTICOSTEROIDS, RELATED STEROIDS AND THEIR WATER SOLUBLE ESTERS BY HUMAN ERYTHROCYTES
Authors: Agarwal K. N. , Carstensen H.
Published: October 2009

The influence of different factors upon the affinity of human erythrocytes for corticosteroids was studied in vitro in a phosphate buffer. Properties connected with the erythrocytes per se were found to be of importance for the binding of the steroids.

Methods were developed for extraction, separation and estimation of water soluble esters of corticosteroids.
CALCIUM AND CITRATE IN THE THYROIDS OF MALE CFN RATS
Authors: Kaellis Eugene , Goldsmith Eli D.
Published: October 2009

A high calcium and citrate concentration is found in rat thyroids. Significant regression equations are developed for the increase in thyroidal citrate concentration with body weight and for the decline of serumal citrate level with body weight.

Treatment with thiourea is found to cause a marked decrease in thyroidal citrate concentration and a decline in thyroidal calcium concentration. The treatment with desiccated thyroid causes an increase in thyroidal citrate concentration but leaves the calcium level unaffected. The serumal citrate level is lowered after two weeks of thiourea treatment but returns to normal at two months. Treatment with desiccated thyroid for one month causes a rise in serumal citrate. Thiourea treatment for two months fails to change the serumal calcium level, but desiccated thyroid treatment for one month causes a decline in this parameter A low iodine diet causes a marked decline in thyroidal citrate concentration, which decline is still greater when calcium carbonate is added to the diet. The thyroidal calcium level remains unaffected by the low iodine diet and rises very sharply with calcium supplementation. The blood citrate and calcium levels are not affected by the low iodine diet, but the addition of calcium causes an increase in the blood calcium level. Inanition for five days causes a decline in serumal calcium and citrate but a rise in thyroidal calcium and citrate.
DEFINITIVE IDENTIFICATION OF MICROQUANTITIES OF RADIOACTIVE STEROIDS BY RECRYSTALLIZATION TO CONSTANT SPECIFIC ACTIVITY
Authors: Axelrod Leonard R. , Matthijssen Charles , Goldzieher Joseph W. , Pulliam Jean E.
Published: October 2009

Studies of steroid metabolism using isotopically-labeled compounds at physiological levels present unique problems in the identification of the metabolites and in the demonstration of their radiochemical purity. The submicrogram quantities of material available preclude the use of classical identification techniques. The character of the evidence obtained, the advantages and disadvantages of chromatographic and countercurrent distribution methods are discussed. Crystallization to constant specific activity is a recognized method for demonstrating that a substance is not radiochemically impure. Its parameters have never been accurately defined. Its true power is achieved only when it is preceded by extensive purification of the material to be characterized. In this way, the unknown material is first categorized by its migration rate in various solvent systems, and then by its crystalline identity with the carrier compound. The likelihood of two dissimilar steroids being both isopolar and isomorphic is held to be remote. Liquid scintillation spectrometry and gravimetry are the techniques used for the determination of constant specific activity. This method for measurement of radioactivity is extremely flexible, sensitive, and lends itself to dual-isotope experiments. Gravimetry under standardized conditions is suitably precise and much more generally applicable than spectroscopic quantitation. The parameters of the technique of rapid, forced microcrystallization are analyzed. In particular, the problem of contamination of crystals is analyzed in detail, and it is pointed out that classical concepts of purification by crystallization, developed chiefly in connection with ionic inorganic materials, must be modified when applied to nonionic steroid compounds. A mathematical analysis of the errors inherent in this technique indicates that 3 successive crystallizations of a pure radioactive compound should yield values for the specific activity which are within ± 5 % of the average of the 3 values.
GONADOTROPIN-INDUCED TWINNING AND RELATED PHENOMENA IN BEEF CATTLE
Authors: Hafez E. S. E. , Jainudeen M. R. , Lindsay D. R.
Published: October 2009

Estrus, ovulatory responses, conception and related phenomena were investigated in Hereford beef cattle treated with exogenous gonadotropins to induce multiple pregnancy. The ovulatory response was judged by the number of corpora lutea estimated by palpation per rectum.

Patterns of behavioral estrus, cervical mucus, metcstrous bleeding and mounting were recorded in untreated cattle. Mounting other cows during diestrus was as frequent as mounting bulls. Thirty-two per cent of the cycles were accompanied by metestrous bleeding; and in 3 per cent of the cycles, bleeding was not at metestrus.

In PMS-treated cattle, the frequency of split estrus was inversely related to the time interval between PMS injection and subsequent estrus; ovulatory response was highest when the interval was 4 days. PMS caused no increase in the frequency of weak estrus or of quiet ovulation. HCG
THE MECHANISMS INVOLVED IN TESTICULAR DEGENERATION IN MAN
Authors: Johnsen Svend G.
Published: October 2009

The study presents a correlation between the regulatory mechanisms of the human testis and a number of factors involved in the degenerative processes in idiopathic hypospermatogenesis. As a working hypothesis, it is assumed that temporary damage cannot result in permanent hypospermatogenesis unless this is maintained by a special mechanism, and the object of the study is to find such a mechanism.

It is shown 1) that in man the full spermatogenetic cycle can take place in the absence of Leydig cells; 2) that decreased spermatogenesis leads to increased release of gonadotrophins and further to Leydig cell hyperplasia; 3) that spermatogenetic lesions do not per se induce deposition of hyaline material in the tubular wall, but that hyalinization damages the epithelium; 4) that a special feature of the structure of the testis in Klinefelter's syndrome strongly suggests that the hyalinization process is not a direct gonadotrophin effect but is related to Leydig cell function. The nature of Leydig cell function has been shown to depend upon the qualitative nature of gonadotrophin stimulation, and findings indicating a qualitative change in the secretion of hyperplastic Leydig cells in hypospermatogenesis are presented.

From these relationships a theory of the pathogenesis of "idiopathic" hypospermatogenesis is advanced. Temporary damage to the germinal epithelium induces increased gonadotrophin release and changes in the FSH/LH ratio. These result in Leydig cell hyperplasia and in qualitative changes in Leydig cell function. This may start a hyalinization process which damages the epithelium, this damage in turn maintains the gonadotrophin rise, etc., etc., The existence of a pathogenetic vicious circle in the human testis affords an explanation for the frequent occurrence of testicular degeneration and permanent cryptogenetic, hypospermatogenesis in man.

The aim of this presentation is to correlate the mechanisms involved in the regulation of testicular function in man with the processes of non-specific testicular degeneration. By a total consideration of a large number of factors an attempt will be made to arrive at an explanation of the frequent occurrence of testicular degeneration in man. Although testicular degeneration has frequently been dealt with in the literature (cf. below), no such attempt has apparently been published.
ATYPICAL ADRENAL HYPERFUNCTION: IN VIVO STUDIES AND INCUBATIONS OF ADRENAL TISSUE WITH 4-14C PROGESTERONE
Authors: Goldzieher Joseph W. , Axelrod Leonard R. , Weissbein Arthur S.
Published: October 2009

Six women with atypical forms of adrenal cortical hyperfunction were studied by means of urinary excretion of 17-ketosteroids and 17-hydroxycorticoids and their response to ACTH stimulation and corticosteroid suppression. Unusual responses were observed, particularly with respect to the independence of 17-KS and 17-OHCS excretion. The adrenals of 3 patients were anatomically normal whereas the others showed hyperplasia. Minced adrenal tissue was incubated with 4-14C progesterone and the metabolites isolated and definitively identified. The pattern of biosynthesized corticosteroids showed great variation, and in some instances clarified certain clinical features. The pattern of certain C19-metabolites could not be studied adequately because of the use of a Δ4 rather than a Δ5 substrate.
Enzymic Correlates of Development, Secretory Function and Regression of Follicles and Corpora Lutea in the Bovine Ovary. PART II: Formation, Development and Involution of Corpora Lutea
Authors: Lobel B. L. , Levy E.
Published: October 2009

Activities of various hydrolases and dehydrogenases were studied during the formation, development and involution of cyclic corpora lutea and in the corpora lutea of early pregnancy. At 24 hours postovulation the luteal cells, whether of granulosal or thecal origin, contained demonstrable levels of Δ5-3β-hydroxysteroid dehydrogenase and the NADP and NADPH2 diaphorases. During the period of proliferation and cellular growth, enzymic activities in the luteal cells were moderate at first, and then increased. In the mature corpus luteum, activities of the dehydrogenases occurred in all luteal cells but were most intense in the large polymorphic luteal cells. Activities of hydrolytic enzymes, low in the immediate postovulatory period, increased with the development of the vascular system. Enzymic characteristics of corpora lutea of gestation were similar to those of cyclic corpora, except for phosphorylase activity which was observed in luteal cells in gestational corpora, but confined to the vascular walls in cyclic corpora. No increase in activities of 17β- and 20β-hydroxysteroid dehydrogenases (above those seen in pre-ovulatory follicles) were observed after incubation of sections of either mature cyclic or gestational corpora. Involution of cyclic corpora lutea began with degenerative changes in the blood vessels: pyknosis of the endothelial cell nuclei and a sudden decline in activities of hydrolytic enzymes in the vascular walls. Subsequently, the luteal cells showed a sharp decrease in activities of the dehydrogenases as well as other signs of regressive change. The cytochemical findings are discussed in relation to biochemical observations on steroid synthesis by the bovine corpus luteum.
AGGLUTINATION INHIBITION REACTIONS FOR THE DETERMINATION OF GONADOTROPHINS
Authors: Schuurs A. H. W. M.
Published: October 2009

Various techniques for sensitising erythrocytes and latex particles with gonadotrophins, particularly with HCG, are described.

The haemagglutination inhibition reactions are generally interpreted by means of »erythrocyte settling patterns«. By a new method of evaluating these patterns a relatively precise quantitative determination is possible. Latex agglutination inhibition reactions on slides are particularly suitable as rapid qualitative tests.

In cases where the maximum attainable sensitivity of the agglutination inhibition tests is insufficient, e. g. for determining LH concentrations in urine, the hormone in the test fluid has to be concentrated or extracted. An alternative method is a modified haemagglutination inhibition test for large volumes which is applicable to unconcentrated urine.

Due to non-specific inhibitions the above-mentioned tests cannot be applied to unprocessed serum.

Agglutination inhibition tests with HCG are already well advanced, pregnancy diagnosis being their main application. Now that highly purified HCG is available, a satisfactory specificity for these tests can be attained.

If the immune system for HCG is used for estimating LH, it has to meet additional specificity requirements. Furthermore, the measure of cross-reaction and the choice of standard merit special attention.

Finally, a literature survey is given of test systems in which LH and FSH were used as antigens.
ASSESSMENT OF RADIOIODINATED HORMONE PREPARATIONS
Authors: Hunter W. M.
Published: October 2009

The preparation of radioiodinated human LH and human FSH with specific activities of 50—150 μc/μg for use in specific radioimmunoassay systems is described. Methods for minimising iodination damage, for removing severely damaged fractions after iodination and for assessing the immunological reactivity of the final products are detailed. The obligation upon immunoassayists to demonstrate that their labelled preparations do indeed represent the hormones under consideration is discussed and criteria which may contribute evidence on this question are put forward.